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*** First International Symposium on Apitherapy, Madrid, Spain, 1974.

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Kalman, Ch. (1983) (Israel) – Apitherapy succes in Israel,
in the XXIX-Th. Apimondia Congress, Budapest, Hungary (***-abstract in Kaal 1987, p.36).

Kaminski, M.; Scheller, Stanislaw; Nolewajka, E. (1977) – Biological properties and clinical application of propolis. V. The action of ethanol extract of propolis (EEP) on laboratory animals. Histochemical investigations,
in Arzneimittelforschung, 27(10), pp.1962-64 (***-abstract). [liv]

Kanasiriova; Vasiliov, V. (1976) (Bulgaria) – Traitement de rhino-pharyngites aigues par la propolis,
in the Second International Symposium on propolis, Bratislava, Czechoslovakia.

Kardakov, V. P. (1980) – Propolis, amino-acids and European foul brood,
in Tekhnol. Proizvod. Prod. Pcelovodstvo, pp.151-53.

Karimova Z. H.; Beris, M. T.; Starosevskaia K. B. (1960) (USSR) – The antimicrobially action of some propolis products,
in Tezele rep. Congres Apicult. Med., Leningrad, USSR, pp.82-83 (citata de Alina Derevici).

Karimova Z. H. (1961) (USSR) – About the medicinal qualities of propolis (Russian),
in Pcelovodstvo, 38(8), p.32 (***); (B, AA426L/64)
Romanian translation by Epsih Sidor (***).

Karimova Z. H.; Rodionova E. I. (1963)(USSR) – Lung tuberculosis and propolis (Russian),
in Pcelovodstvo, 40(1), pp.36-37 (***); (B, AA661/64)
Romanian translation by Epsih Sidor (***).

Karimova Z. H. (1970) (USSR) – Propolis als Medizin (German),
in Imkerfreund, #8 (translation from Pcelovodstvo by Hartmann).

Karimova Z. H.; Rodionova E. I. (1971, 1978, 1981, 1990) (USSR) – Propolis in the complex treatment of bronchial, pulmonary and extra-pulmonary tuberculosis,
in the XXIII-Rd. Apimondia Congress, Moscow, USSR, 1971;
in “Propolis, a remarkable hive product”, Apimondia Publishing House, Bucharest, Romania, 1978, pp.169-71 (***);
in “Propolis”, Editura Apimondia, Bucuresti, editia a treia, 1981, pp.185-88 (Romanian) (***) si in editia a IV-a, 1990, pp.221-23 (Romanian) (***).

Kawa, M. N. (1996) (Tanzania) – Development research on propolis as an effective cure against malaria and other human and domestic animal diseases,
in the International Conference on Bee Products: Properties, Applications and Apitherapy, Tel – Aviv, Israel, May 26-30, 1996.

Kedzia, A. (1986) – Effect of ethanol extract of propolis (EEP) on anaerobic bacteria,
in Herba polonica 32 (1), pp.53-58.

Kedzia, A. (1988) (Poland) – Estimation of the effectiveness of ethanol extract of propolis on obligate anaerobes of oral cavity,
in Czas-Stomatol., Dec. 41(12), pp.757-62.

Kedzia, B.; Holderna, E. (1987) (Poland) – Recherches sur l’action combinee de la propolis et des medicaments antimicotiques dans la Candida albicans (abstract),
in the XXXI-St Apimondia Congress, Warsaw, Poland, p.530 (***).

Kern, Maks (1976, 1989) (Yugoslavia) – Hive products as drugs in human medicine,
in the Second International Symposium on Apitherapy, Bucharest, Romania, 1976, pp.196-97 (***);
in “Produsele stupului hrana, sãnãtate, frumusete”, Editura Apimondia, 1989, pp.127-28 (***).

Kern Maks; Soba Erika; Budihna, M. (1978) (Yugoslavia) – Apikompleks, a prophylactic product against radiomucositis,
in the Third International Symposium on Apitherapy, Portoroz, Yugoslavia, 1978, pp.338-40(French), pp.340-41(English abstract), p.341(German, Russian and Spanish abstract) (***).

Khachaturov, A. A.; Gudkov, A. I. (1969) (USSR) – Propolis therapy of certain dermatoses and burns in the far north (Russian),
in Vestn.-Dermatol.-Venerol., Feb., 43(2), pp.63-65.
(BS 1970, 31 : 1503).

Khadzai, Ya. I.; Obolentseva G. V.; Serdyuk, A. D. (1969) (USSR) – Pharmacology of acacetin (Russian),
in Farmak. Toks. (Moscow), 32, p.451-53. (CA 71 : 79508u).

Khalikova N.V.; Grankina, N. V.; Frolova, T. A. (1988) (USSR) – Use of a propolis-containing paste for filling root canals in treatment of pulpitis,
in Stomatologiia (Moscow), Nov.-Dec. 67(6), pp.52-53.

Khayyal, M. T.; El-Ghazaly, M. A.; El-Khatib, A. S. (1993) – Mechanism involved in the anti-inflammatory effect of propolis extract,
in Drugs Exp. Clin. Res., 19(5), pp.197-203 (***-abstract). [lv]

Kholodova Y. D. et al. (1981) – Squalene, lanosterol and cholesterol of propolis and its probable sources,
in Khim. Biol. Nauki (5), pp.88-90.

Kirienko, N. D.; Tcherkasova A. I.; Zaharteva L. I.; Gladtchun, V. P.; Klevanik, V. A.; Kiiko, L. A. (1989) (USSR) – Complex treatment of chronic bronchitis with apicultural products (abstract)(French),
in the XXXII-Nd. Apimondia Congress, Rio de Janeiro, Brazil, p.523-24 (***); [lvi]
in Kaal 1991, p.35 (***-abstract).

Kivalkina V. P. (1959) (USSR) – Stravnitelnoe izuchenie protivomikrobnykh svoistv razlichnykh obraztsov propolisa (Russian),
in UC. Zap., Kaz. Gos. Vet. In-ta, tom 74, 127.

Kivalkina V. P. (1959) (USSR) – Antibioticheskie i lechebnye svoistva propolisa (Russian),
in Pcelovodstvo, 6.

Kivalkina V. P. (1963) (USSR) – La propolis et ses effets antibactériens et curatifs,
in the XIX-Th. International Beekeeping Congress, Praga, Czechoslovakia, p.64.

Kivalkina V. P. (1964) (USSR) – Propolis: Its Antibacterial and Therapeutic Properties.
Kasan Publishing Co., USSR.

Kivalkina V. P. (1969) (USSR) – Effect of propolis on immuno–biological reactivity (abstract),
in the XXII-Nd. Apimondia Congress, München, Germany, p.463 -64(***). (B, AA666/70).

Kivalkina V. P.; Gorshunova V. P. (1969) (USSR) – Combined action of antibiotics and propolis on Staphylococcus aureus and Escherischia coli (Russian),
in Fitontsidi, Mater. Soveshch., 6, pp.103-05. (CA 78 : 53206p).

Kivalkina V. P.; Balalykina V. I.; Piontkovski (1971, 1978, 1981, 1990) (USSR) – Plasmocitary response in White Mice Immunized with an antigen associated with propolis,
in the XXIII-Rd. Apimondia Congress, Moscow, USSR, 1971;
in “Propolis, a remarkable hive product”, Apimondia Publishing House, Bucharest, Romania, 1978, p.107-11 (***);
in “Propolis”, Editura Apimondia, Bucuresti, editia a treia, 1981, p.132-36 (Romanian) si in editia a IV-a, 1990, p.100-03 (Romanian) (***).

Kivalkina V. P.; Budarkova E. L. (1971, 1978) (USSR) – Adjuvant effect of propolis used for immunisation in combination with tetanus anatoxin,
in the XXIII-Rd. International Apicultural Congress of Apimondia, Moscow, USSR, 1971, p.16;
in “Propolis, a remarkable hive product”, Apimondia Publishing House, Bucharest, Romania, 1978, pp.104-07 (***).

Kivalkina V. P. (1971) (USSR) – The adjuvant effect of propolis in tetanus toxoid immunisation,
in Veterinary, Nov. 11, pp.45-46.

Kivalkina V. P.; Gorshunova V. I. (1973) (USSR) – The possibility to use propolis combined with antibiotics (abstract),
in Antibiotiki (Moscow), 18(3), pp.261-63 (Russian); B, AA877/75;
in the XXIV-Th. Apimondia Congress, Buenos Aires, Argentina, p.424 (***).

Kivalkina V. P.; Barskov, A. A.; Gubkina N. I.; Talan, V. A.; Dubovenko, J. V.; Schmidt, E. N. (1975) (USSR) – Propolis fractionating and the study of the microbicidal action of the fractions,
in the XXV-Th. Apimondia Congress, Grenoble, France, pp.225-29 (***).

Kivalkina, V. P.; Bodarkova, E. L. (1975) (USSR) – Effect of propolis on antigenic and immunogenic properties of tetanic anatoxin,
in Fitrolisidy eksperimental mye-isstedovayz Vop Eroos teorii Praktik. Ed. B.E. Alzemman. Kiev Ukrrsinion SSR Neukouo Dumka: 269-270 Karna Veterinary Institut.

Kivalkina V. P. (1976) (USSR) – Fractionation of the mixture of volatile with steam components of propolis and the study of their antimicrobial activity,
in Antibiotiki, May, 21(5), pp.422-23.

Kivalkina V. P.; Barskov, A. A. (1976) (USSR) – Propolis preparations for medical use,
in Pcelovodstvo, 8;
in French translation by M. Georges Crozat (***).

Kivalkina V. P. (1976, 1978) (USSR) – Balance-sheet and prospects of the study of propolis,
in the Second International Symposium on Apitherapy, 1976, Bucharest, Romania, pp.197-202 (***);
in “Propolis – a remarkable hive product”, Apimondia Publishing House, Bucharest, 1978, pp.111-16 (***);
in “Propolis”, Editura Apimondia, Bucuresti, editia a treia, 1981, pp.128-32 (Romanian) (***).

Kivalkina V. P.; Belozerova G. A.; Kamalov, G. H. (1978) (USSR) – Stimulation of immunogenesis with propolis in the immunisation of animals against AUJESZKI disease,
in the Third International Symposium on Apitherapy , Portoroz, Yugoslavia, 1978; Russian, pp.176-180; French, p.180 (abstract); English, pp.180-81 (abstract); German and Spanish, p.181 (abstract) (***).

Kivalkina V. P. (1981) (USSR) – La propolis, un precieux remede naturel (abstract),
in the XXVIII-Th. Apimondia Congress, Acapulco, Mexico, p.458 (***).

Kivalkina V. P. (1980, 1981) (USSR) – The propolis is necessary to the human beeings and to the bees (Romanian),
in Apiacta 15 (3), p.117;
in “Propolis”, Apimondia Publishing House, Bucharest, 1981, pp.18-21 (***).

Kivman, G. Ia. (1978) – Method of determining the antimicrobial activity of alcohol extracts of propolis,
in Antibiotiki, 9, 23(9), pp.792-94 (***-abstract).

Kleinhans, D. (1987) – Airborne contact dermatitis due to propolis,
in Contact Dermatitis, Sept., 17(3), pp.187-88.

Kleinrok, Z.; Borzecki, Z.; Scheller, Stanislaw; Matuga, W. (1978) – Biological properties and clinical application of propolis.(X). Preliminary pharmacological evaluation of ethanol extract of propolis (EEP),
in Arzneimittelforschung, 28(2), pp.291-92 (***-abstract).

Knopf, E.; Ogait, A. (1961) – Warum eignet sich das deutsche Propolis nicht ohne weiteres zum Lackieren von Streichinstrumenten ?
in Instrumentenbau Zeitschrift, pp.152-154-156-158-160.

Kolesnikova M. A.; Breeva, L. G.; Sokolova, I. V. (1984) (USSR) – Preparations of copper and propolis in the complex treatment of diseases of the cornea,
in Oftalmol.-Zh., (2), pp.121-23.

Kolev, J.; Dimtcheva Vera (1997) (Bulgaria) – Beeswax with propolis treatment on patients having low back pain,
in the XXXV-Th. Apimondia Congress, Antwerp, Belgium.

Korbar-Smid, J.; Sumer-Toldi, D. (1978) (Yugoslavia) – Experiments for developing and testing effectiveness of medicines with propolis,
in the Third International Symposium on Apitherapy, Portoroz, Yugoslavia, 1978, pp.60-62; French abstract, p.63; German abstract, pp.63-64; Russian and Spanish abstract, p.64 (***).

Korcsog, M.; Calauz, S. (1983) (Romania) – Étude toxicologique de l’extrait total standardisé de propolis (abstract),
in the XXIX-Th. Apimondia Congress, Budapest, Hungary, p.136 or 422 (***).

Korfei, A.; Burducea, O.; Crisan, I. (1980) (Romania) – Investigations concerning the action of several chemical and biological agents on HBsAg,
in Virologie, Oct-Dec., 31(4), pp.273-78 (***-abstract).

Korochkin, I. M.; Poslavskii, M. V. (1986) – Treatment of chronic gastroduodenal ulcers by local administration of propolis,
in Sov.-Med., (10), pp.105-07.

Korsun, V. F. (1983) – Use of propolis in the treatment of trophic ulcers,
in Vestn.-Dermatol.-Venerol., Nov. (11), p.46-48.

Korzybski, T.; Kowszyk-Gindifer, Z.; Kurylowicz, W. (1967) – “Antibiotics” origin, nature, properties,
in Pergamon Press, pp.1456-57.

Kosenko, S. V.; Kosovich, T. (1990) – The treatment of periodontitis with prolonged-action propolis preparations (clinical and x-ray research),
in Stomatologiia (Mosk),Mar.-Apr. 69(2), pp.27-29 (***-abstract) .[lvii]

Kosonocka, L. (1990) – Propolis – snake oil or legitimate medicine?
in American Bee Journal, 130, pp.451-52.

Kotel’nikov V. P. (1989) – The use of propolis in medicine (Russian),
in Feldsher Akush. May; 54(5), pp.46-48.

Kovalik, P. V. (1977) – Bacterial flora and its sensitivity to propolis and antibiotics in acute and chronic highmoritis,
in Zu-Ushn.-Nos.-Gorl.-Bolenz., Jul.-Aug. (4), pp.82-83.

Kovalik, P. V. (1978) – Treatment of chronic suppurative maxillary sinusitis with propolis,
in Zh.-Ushn. -Nos.-Gorl.-Bolenz., Nov.-Dec. (6), p.12-16.

Kovalik, P. V. (1979) – Use of propolis for treatment of chronic sinusitis of fungal aetiology,
in Vestn.-Otorinolaringol., Nov.-Dec.(6), pp.60-62.

König, B. (1985) – Plant sources of propolis,
in Bee World, 66(4), pp.136-39.

König, B.; Dustmann, H. Jost (1986) (Germany) – Propolis und Viren: der gegenwärtige Forschungsstand (Propolis and viruses: current status of a research project),
in Apidologie 17 (4), pp.334-36.

König, B. (1986,1991) (Germany) – Studien zur antivirotischen Aktivität von Propolis (Kittharz der Honigbiene, Apis mellifera),
in Algemeine Deutsche Imker Zeitung, 9/1986;
BSc Dissertation , Hannover, Germany;
in Kaal, 1991, p.21 (***).

Köwing Ernst (1992) (Germany) – Gesundheit durch die Bienen. Die hilfe der Biene zum (Über-) Leben.
Immen Verlag, Oldenburg, Germany, 125 pages; Propolis pages: 27; 29; 59-73; 79-92; 93-95; 111; 113-14; ISBN 3-929193-00-0 (***).

Krasnodebski, J. (1982) – Properties and use of propolis,
in Pol Tyg Lek, 37(49), pp.1489-92.

Krasnodebski, J.; Scheller, Stanislaw; Suchy, H. (1986) (Poland) – Use of an ethanol extract of propolis in the treatment of vaginitis and conditions after electrocoagulation of cervical erosion,
in Ginekol-Pol., Jul. 57(7), pp.471-78.

Kravchuk, P. A. (1968) – Use of propolis in oto-rhino-laryngology (Russian),
in Zh.-Ushn.-Nosov.-Gorlov.-Bolezn., Jan.-Feb. 28(1), pp.97-98.
(IM 1970 : 3681)

Kravchuk, P. O.; Rafalskii, K. P. (1969) – Propolis as a drug (Russian),
in Farmatsevt.-Zh. (Kiev), 24(5), p.87-89. (IM 1970 : 3681).

Kravchuk, I. A. (1971) – Results of use of a propolis extract for chronic subatrophic and atrophic pharyngitis (Russian),
in Zh-Ushn-Nos-Bolezn, Jan.-Feb 31(1), p.73-78. (AA581/76).

Kravchuk, I. A.; Kravchuk, G. P. (1977) – Propolis and its use in oto-rhino-laryngological practice (Russian),
in Zh.-Ushn.-Nos.-Gorl.-Bolezn., (1), pp.87-89.

Krol, W.; Czuba, Z.; Scheller, Stanislaw; Gabrys, J.; Grabiec, S.; Shani, J. (1990) (Poland) – Anti-oxidant property of ethanolic extract of propolis (EEP) as evaluated by inhibiting the chemiluminescence oxidation of luminol,
in Biochemistry International, 21(4), pp.593-97 (***-abstract; ***-Kaal 1987, pp.32-34).

Krol, W. (1993) (Poland) – Synergistic effect of ethanolic extract of propolis and antibiotics on the growth of Staphylococcus aureus,
in Arzneimittelforschung, May, 43(5), pp.607-09 (***-abstract).

Krupicka, P. (1978, 1981, 1990) (Czechoslovakia) – Methods of obtaining propolis,
in “Propolis, a remarkable hive product”, Apimondia Publishing House, Bucharest, Romania, 1978, pp.241-45 (***);
in “Propolis”, Editura Apimondia, Bucuresti, Romania, editia a treia, 1981, pp.287-91 (Romanian) (***) si in editia a IV-a, 1990, pp.22-26 (Romanian) (***).

Kudzak, S.; Widerny, J.; Winiarek, E. (1987) (Poland) – L’importance clinique de la thérapie a propolis en O.R.L. au sanatorium militaire de Ciochocinok (abstract),
in the XXXI-St Apimondia Congress, Warsaw, Poland (***).

Kujumgiev, A.; Bankova Vassya; Ignatova, A.; Popov, S. (1993) (Bulgaria) – Antibacterial activity of propolis, some of its components and their analogues,
in Pharmazie, Oct. 48(10), pp.785-86.

Kujumgiev, A.; Tsvetkova I.; Serkedjieva Yu; Bankova Vassya; Christov, R.; Popov,S. (1999) (Bulgaria[lviii]) – Antibacterial, antifungal and antiviral activity of propolis of different geographic origin,
in Journal of Ethnopharmacology 64, pp.235-240 (***).

Kuriakina, N. V.; Kuriakin, V. V. (1996) – The apitherapy of apical periodontitis,
in Stomatologiia (Mosk), Spec No, pp.63-4.

Kurijan, H.; Bratanov, D. (1978) (Bulgaria) – Use of Stomapin, a preparation with propolis, in post extraction affection of tooth socket,
in the Third International Symposium on Apitherapy, Portoroz, Yugoslavia, 1978; Russian, pp.118-20; French, p.120(abstract); English, German and Spanish, p.121 (abstract) (***).

Kurijan, Gh. (1978, 1981, 1990) (Bulgaria) – New biological bandage for mouth cavity mucosa based on propolis,
in “Propolis, a remarkable hive product”, Apimondia Publishing House, Bucharest, Romania, 1978, pp.150-53 (***);
in “Propolis”, Apimondia Publishing House, Bucharest, III-Rd. edition, 1981, pp.188-92 (Romanian) (***) and in the IV-Th. edition, 1990, pp.208-12 (Romanian) (***).

Kurilin, I. A. (1972) – Propolis treatment of non-healing post-trephining cavities following radical surgery and tympanoplasty,
in Vestn.-Otorinolaringol., Mar.-Apr. 34(2), pp.57-59.

Küstenmacher (1911) – Propolis,
in Ber. dt. pharm. Ges., 21(1), pp.65-92. (B, CA 5 : 2983).

Lafon, L. (1970) – Ger. Offen. 2 010 505 CA 73: 120501t.

Lambert, Priscila (1999) (Brazil) – Pesquisa mostra que resina produzida pelas abelhas impede o crescimento de células cancerígenas. Própolis pode proteger corpo de tumores,
in Folha de São Paulo, 12 de Julho de 1999 (***). [lix]

Lambert, Priscila (1999) (Brazil) – Própolis puede proteger del sol,
in Folha de São Paulo, 12 de Julho de 1999 (***). [lx]

Lambert, Priscila (1999) (Brazil) – Carie en ratones fué reducida,
in Folha de São Paulo, 12 de Julho de 1999 (***).[lxi]

Langstroth, L. L. (1891) – L’Abeille et la Ruche.
Maison Rustique, Paris, p.142.

Larion, M.; Larion Cornelia; Moldovanu, C. (1983) (Romania) – Observation concernant l’utilisation de la propolis en gynécologie,
in the XXIX-Th. Apimondia Congress, Budapest, Hungary, pp.422-24 (***).

Lavie, P. (1957) (France) – Étude des substances antibiotiques presentes chez Apis mellifica et chez quelques insectes sociaux,
in C.r. Acad. Sci., Paris, 244, pp.2653-55. (B, AA259/59).

Lavie, P. (1960) (France) – Les substances antibacteriennes dans la colonie d’abeilles (Apis mellifica L.).
Thesis. d’Apiculture. Station experimentale d’Apiculture. Montfavet, France. 299 pp.

Lavie, P. (1960) (France) – Les substances antibactérienes dans la colonie d’abeille (Apis mellifica L.),
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  (EB, AA 761/63).

Lavie, P. (1968) (France) – Traité de biologie de l’Abeille.
Masson et Cie. Tomme 3, pp.1-115.

Lavie, P. (1969) (France) – On the origin of propolis (abstract),
in the XXII-Nd. Apimondia Congress, Munich, Germany (***).

Lavie, P. (1973) (France) – Sur l’origine de la propolis,
in Revue Française d’Apiculture, no. 305, Jan., pp.19-21.

Lavie, P. (1975, 1977, 1981, 1990) (France) – The relationship between propolis, poplar buds (Populus sp.) and castoreum,
in the XXV-Th. Apimondia Congress, Grenoble, France, 1975, p.229-33 (***);
in Abeilles et fleurs, 2, 1977, p.567;
in “Propolis”, Editura Apimondia, Bucuresti, editia a treia, 1981, pp.46-49 (Romanian) (***) si in editia a IV-a, 1990, pp.44-47 (Romanian) (***).

Lavie, P. (1975) (France) – L’antibiotique de propolis,
in “Propolis”, Apimondia Publishing House, Bucharest, p.43.

Lavie, P. (1975, 1978) (France) – Propolis antibiotics,
in “Propolis”, Apimondia Publishing House, 1975, pp.34-50;
in “Propolis – a remarkable hive product”, Apimondia Publishing House, 1978, pp.41-48 (***).

Lavie, P. (1980) (France) – The antibiotic, antigerminative and biological properties of propolis,
in Round table on Propolis, May 9-11,1980, Bucharest, Romania.

Lavie, P. (1981, 1990) (France) – The antibiotic, antifungal and phytoinhibitory properties of propolis (Romanian),
in “Propolis”, Apimondia Publishing House, III-Rd. edition (1981), pp.99-108 (***) and in IV-Th. Edition (1990), pp.62-69 (***).

The Lawrence Review: Propolis Monograph. The Lawrence Review of Natural Products, 1996 (reprint)

Lebeda, D. (1978, 1981) (Yugoslavia) – Propolis, an unpoisonous product,
in the Third International Symposium on Apitherapy, Portoroz, Yugoslavia, 1978, p.77-79 (French); English, p.79 (abstract); German, Russian and Spanish, p.80 (abstract) (***);
in “Propolis”, Editura Apimondia, editia a III-a, Bucuresti, 1981, pp.21-23 (Rom.) (***).

Leger,H., Babin,R., Beauvieux,J., Coustou,F. (1960) (France) – L’action de certains derivés flavoniques et de leurs chélates sur l’armature élastique des arteres,
in Therapie, France, XV, pp.1085-95.

Leipus, I. (1975) (USSR) – Treatment of malignant tumours and ulcers with propolis (abstract),
in the XXV-Th. Apimondia Congress, Grenoble, France, p.233 (***).

Leipus, J. K. (1978, 1981, 1990) (USSR) – Propolis, an efficient method of treatment,
in “Propolis, a remarkable hive product”, Apimondia Publishing House, Bucharest, Romania, 1978, p.132 (***);
in “Propolis”, Editura Apimondia, Bucuresti, Romania, a treia editie, 1981, pp.192-93 (Romanian) (***) si in editia a IV-a, 1990, pp.168-69 (Romanian) (***).

Lejeune,B., Vennat,B., Regerat,F., Gardelle,D., Fousher,D., Pourrat,A. (1984) (France) – Propolis extracts and utilisation in shampoos and lotions,
in Parf. Cosm. Aromes, 56, pp.65-68.

Lemaire (1918) (France) – Les produits du rucher.
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Lepekhin, V. N.; Leonova T. A. (1970) – Antimicrobial properties of propolis,
in Stomatologiia, Jul.-Aug. 49(4), pp.16-19.

Li, M. W.; Yudin, A.I.; Vande Voort, C. A.; Sabeur, K.; Primakoff, P. and Overstreet, J. W. (1997) – Inhibition of Monkey Sperm Hyaluronidase Activity and heterologous Cumulus Penetration by Flavonoids,
in Biol. Reprod. 56 (6), pp.1383-1389.

Likar, M.; Filipic, B. (1979) (Yugoslavia) – Some further studies on the use of propolis, royal jelly and pollen (abstract),
in the XXVII-Th. Apimondia Congress, Athens, Greece, p.487 (***).

Likar, M.; Vukmirovic, V. (1983) (Yugoslavia) – Étude microbiologique des preparations a la propolis (abstract),
in the XXIX-Th. Apimondia Congress, Budapest, Hungary, p.142 (***).

Lin, S. C.; Lin, Y. H.; Chen, C. F.; Chung, C. Y.; Hsu, S. H. – The hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries,
in Am J Chin Med, 25(3-4), pp.325-32 (***-abstract). [lxii]

Lindenfelser, Lloyd A. (1967) (U.S.A.) – Antimicrobial activity of propolis,
in American Bee Journal, 107(3), pp.90-92 (***)
(B, AA400/67).

Lindenfelser, L. A. (1968) – In vivo activity of propolis against Bacillus larvae,
in J. Invert. Path., 12, pp.129-31. (B, AA792/69).

Liusov, V. A.; Zimin, Iu. V. (1983) – Experimental rationale and trial of the therapeutic use of bee-raising products in cardiovascular diseases,
in Kardiologia, May, 23(5), pp.105-10.

Lolin Miroslava, Panjevic Tatjana, Dimitrijevic´,M., Trbic´,B. (1979) (Yugoslavia) – Propolis fraction activity on Mycobacterium tuberculosis (abstract),
in the XXVII-Th. Apimondia Congress, Athens, Greece, p.488 (***).

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Pfeiffer Constanta Nely (1993) (Romania) – The bee products in cosmetics (Romanian),
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Pidoux, Michel (1984) (France) – Teinture mere et extrait mou (propolis),
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Pisarev, I.; Dimitrova Milka (1975) (Bulgaria) – Treatment of parodontopathies by electrophoresis with propolis (abstract),
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Pokorn, D.; Vukmirovic Vera (1979) (Yugoslavia) – Effect of propolis on glucose emptying from rats’ stomachs,
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Polyakov, V.V.; Shukenova, R. ZH.; Orlov, V.K. (1988) – Fatty acids in propolis,
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Popescu,D., Iliesiu,N.V., Bojor,Ov. (1982) (Romania) – Medicinal product with liver & gall bladder protective action (Romanian),
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Popescu Filofteia, Palos Elena, Mateescu Cristina (1987) (Romania) – Research regarding an ophtalmic drug (Oftalmosept) based on propolis (Romanian),
in Romania apicolã, 8, p.30 (***-abstract).

Popescu Filofteia (1990) (Romania) – “Acneol”, dermato-cosmetical product for acne treatment (Romanian),
in “Propolis”, Apimondia Publishing House, Bucharest, Romania, 1990, pp.294-96 (***).

Popescu Filofteia (1991) (Romania) – Research regarding the propolis suppositories – Miprosept (Romanian),
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Popescu,M.P., Palos Elena, Popescu Filofteia (1981) (Romania) – Traitement a la propolis en aerosols de quelques affections du pole anterieur de l’oeil (abstract),
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Popescu,M.P., Palos Elena, Popescu Filofteia (1985) (Romania) – The results obtained following application of eye preparations (Colmel, Colgel, Oftalmosept) with biologically active honeybee products in palpebro-corneo-conjunctival diseases,
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Popescu, M. P.; Palos, E.; Popescu, F. (1985) – Studiul eficacitatii terapiei biologice complexe cu produse apicole in unele afectiuni oculare localizate palpebral si conjunctival in raport cu modificarile clinico-functionale [Study of the efficiency of biological therapy with honey bee products in some palpebral and conjunctival affections in terms of clinical-functional changes],
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Popescu,M.P., Alexandra Dana, Popescu,M. (1987) (Romania) – L’application des micelles moléculaires des produits apithérapiques dans quelques affections oculaires,
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Popescu,M.P., Palos Elena, Popescu Alexandra Dana, Ardeleanu Aura (1987) (Romania) – The molecular mycelium of biologically active apitherapeutical products applied in some ocular diseases,
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Popescu,M.P., Palos Elena, Popescu Filofteia (1987) (Romania) – Eficacité de la thérapeutique biologique complexe par les produits apicoles dans certaines affections oculaires,
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Popescu,M.P., Alexandra,D., Popescu,M., Palos Elena, Popescu Filofteia (1987, 1990) (Romania) – Retablissement de l’homeostasie oculaire dans les affections de la sclerotique et de l’iris a l’aide de produits apitherapiques biologiquement actifs (abstract),
in the XXXI-St. Apimondia Congress, Warsaw, Poland, 1987, pp.564-65 (***);
in “Propolis”, Apimondia Publishing House, Bucharest, Romania, IV-Th. edition, 1990, pp.149-58 (Romanian) (***).

Popescu,M.P., Popescu Alexandru Dana, Popescu,M., Palos Elena, Popescu Filofteia (1989) (Romania) – Use of the bee products in the treatment of incipient lens opacities (abstract),
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Popescu,M.P., Popescu Dana Alexandra (1992) (Romania) – Tratamentul cataractei oculare cu produse apicole (Romanian),
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Popescu,M.P., Popescu,Dana (1994) (Romania) – Ophtalmo-apitherapy (Romanian),
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Popescu,Mircea Petre, Popescu Alexandra (1997) (Romania) – Le traitement de la cataracte oculaire aux produits apicoles appliqué sous forme de myceliums moléculaires. Résultats obtenus sur une période de 21 ans,
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in the First International Symposium on Apitherapy, Madrid, Spain, 1974;
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Popescu V., Paunescu Tamara, Maftie I., Velescu Gh., Tataran M. (1975) (Romania) – The first results obtained with local apiphytotherapy in the haemorrhages caused by teeth extraction in patients with coagulation troubles,
in the XXV-Th. Apimondia Congress, Grenoble, France, pp.243-244 (***).

Popescu, V., Ghitescu Iulia, Maftei, I., Paunescu Tamara (1976) (Romania) – Apiphytotherapeutic treatment of the chronic parotidean-masseterin inflammations,
in the Second International Symposium on Apitherapy, Bucharest, Apimondia Publishing House, pp.260-63 (***).

Popescu,V., Paunescu Tamara, Velescu,G., Maftei,I. (1976) (Romania) – Determination of the activity of anaerobic transhydrogenases and hydrogen donor substances of propolis, in the Second International Symposium on Apitherapy, Bucharest, Romania, pp.202-07 (***).

Popescu, Vasile (1987) (Romania) – Diversificarea productiei apicole, cale sigura de sporire a eficientei economice si rentabilitatii tuturor stupinelor (Romanian),
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Popeskovic,D., Dimitrijevic,M., Soldatovic,B. (1976, 1978, 1981, 1990) (Yugoslavia) – The effect of propolis fractions on some biological systems (I),
in the Second International Symposium on Apitherapy., Bucharest, Romania, 1976, Apimondia Publishing House, pp.220-22 (***);
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in “Propolis”, Editura Apimondia, Bucuresti, editia a treia, 1981, pp.136-37 (no table) (Romanian) (***) si in editia a IV-a, 1990, pp.103-04 (Romanian) (***).

Popeskovic,D., Dimitrievic,M., Soldatovic,B., Stoianovic,N. (1977) (Yugoslavia) – Further investigation on the effect of propolis fractions on some biological systems (II),
in the XXVI-Th. Apimondia Congress, Adelaide, Australia, p.246-48 (***).

Popeskovic,D., Kepcija,D., Dimitrijevic,M., Stojanovic,N. (1978, 1981,1990) (Yugoslavia) – A contribution in the study of propolis fractions. Antioxidant level (I),
in the Third International Symposium on Apitherapy, Portoroz, Yugoslavia, 1978; French, pp.81-83; English, p.83; German, p.84 (***);
in “Propolis”, Editura Apimondia, editia a treia, Bucuresti, 1981, pp.57-59 (Rom.) (***) si in a IV-a editie, 1990, pp.55-58 (Rom.) (***).

Popeskovic,D., Khanfar,M., Petrovic,Z., Dimitrijevic,M. (1978) (Yugoslavia) – Study of the action of propolis fractions against in vitro growth of Trichomonas (T. vaginallis, T. gallinae and T. microti),
in the Third International Symposium on Apitherapy, Portoroz, Yugoslavia, 1978; French, pp.153-55; English abstract, pp.155-56; German, Russian and Spanish abstracts, p.156 (***).

Popeskovic,D., Kepcija,D., Dimitrijevic,M., Stojanovic,N. (1980) – The antioxidative properties of propolis and some of its components,
in Acta Veterinaria (Beograd), 30, pp.133-36.

Popnikolov,P., Potchinkova Pavlina, Donchev,St. (1972, 1978, 1981, 1990) (Bulgaria) – The treatment of mesotympanitis with propolis,
in the First International Symposium on Propolis, Bratislava, 1972, pp.45-47;
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in “Propolis”, Editura Apimondia, Bucuresti, editia a treia, 1981, pp.225-26 (Romanian) (***) si in editia a IV-a, 1990, pp.180-81 (Romanian) (***).

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Popova Milena; Bankova Vassya; Chimov, A.; Vides Silva, M. (2002) (Bulgaria, El Salvador) – A scientific note on the high toxicity of propolis that comes from Myroxylon balsamum trees,
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Popovici,N., Oitã,N. (1976, 1978, 1981, 1990) (Romania) – Influence of some extracts of propolis on mitosis in Allium Cepa L. merisistems,
in the Second International Symposium on Apitherapy, Bucharest, Romania, 1976, pp.349-52 (***);
in “Propolis, a remarkable hive product”, Apimondia Publishing House, Bucharest, Romania, 1978, pp.101-104 (***);
in “Propolis”, Editura Apimondia, editia a treia, Bucuresti, 1981, pp.137-40(Rom.) (***) si in editia a IV-a, 1990, pp.104-08 (Rom.) (***).

Popovici,C., Saraga,M. (1976, 1978, 1981, 1990) (Romania) – Treatment with propolis and other hive products of some otorhynolaryngological affections,
in the Second International Symposium on Apitherapy, Bucharest, Romania, 1976, pp.210-13 (***);
in “Propolis – a remarkable hive product”, Apimondia Publishing House, Bucharest, 1978, pp.198-202 (***);
in “Propolis”, Apimondia Publishing House, 1981, III-Rd. edition, pp.226-30 (Romanian) (***) and in the IV-Th. edition, 1990, pp.181-85 (Romanian) (***).

Popovici, E. (1976) (Romania) – Use of propolis in oto-rhyno-laryngology,
in Rev-Chir (Otorhynolaryngol.), Oct-Dec. 21(4), pp.309-11.

Popovici,C.; Paunescu, C. (1981) (Romania) – Treatment with bee products in acute and chronic pharyngo-laryngopathies,
in Rev-Chir (Otorhynolaryngol.), Jan-Mar, 26(1), pp.71-75.

Popovici,C., Tomescu,E. (1984) (Romania) – Treatment with bee products in chronic nasal and pharyngeal diseases (Romanian), in Rev-Chir (Otorhynolaryngol.), Jan-Mar. 29(1), pp.55-59.

Popovici,C., Palos Elena, Popescu Filofteia, Mateescu Cristina (1985, 1987, 1990) (Romania) – Apitherapeutical treatment used in the acute inflammations of the pharynx and the larynx,
in Apiacta, 4/1985, pp.109-12 (***);
in *** Revue Française d’Apiculture, # 465, 7-8/1987 (Supplement “Aujourd’hui l’Apitherapie”);
in “Propolis”, Apimondia Publishing House, Bucharest, Romania, IV-Th. edition, 1990, pp.158-62 (Romanian) (***).

Popovici,C., Palos Elena, Popescu Filofteia (1990) (Romania) – Therapeutically plan for acute and chronic rhino-sinusal diseases and especially for rhino-sinusal and bronchic allergies with apitherapic products based on propolis (Romanian),
in “Propolis”, Apimondia Publishing House, Bucharest, Romania, IV-Th. edition, 1990, pp.163-66 (***).

Popovici, C. (1991) (Romania) – Apitherapy in the superior breathing passages diseases (Romanian),
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Popovici, C. (1994) (Romania) – Apitherapy in oto-rhinolaryngology (Romanian),
in “Apitherapy in Romania”, Apimondia Publishing House, Bucharest, pp.114-132 (***).

Poppe, B.; Michaelis, H. (1986) – Results of a twice-yearly controlled oral hygiene activity using a propolis-containing toothpaste (double-blind study),
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Popravko,S.A. (1969) (USSR) – Vydelenije i identifikatsia osnovnykh komponentov propolisa (Russian),
in “Doklady sovetskich uchenych i spetsialistov po pchelovodstvu”, Moscow, pp.231-33.

Popravko,S.A., Gurevitch,A.I., Kolosov,M.N. (1969, 1971) ( USSR) – Isolation and identification of basic components of propolis,
in the XXII-Nd. Apimondia Congress, Munich, 1969 (abstract) (***);
in the XXIII-Rd. International Beekeeping Congress, Moscow, USSR, 1971. (AA 665/70).

Popravko,S.A., Gurevitch,A.I., Kolosov,M.N. (1969) (USSR) – Flavonoidnye komponenty propolisa (Russian),
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Cormier, M. (1994) – Comparison of the anti-herpes simplex virus activities of propolis and 3-methyl-but-2-enyl caffeate,
in the J Nat Prod May,57(5), p.644-7 (***-abstract).

The in vitro activity against herpes simplex virus type 1 of 3-methyl-

but-2-enyl caffeate isolated from poplar buds or prepared by synthesis was

investigated. Under conditions of one or multiple multiplication cycles,

this compound, which is a minor constituent of propolis, was found to

reduce the viral titer by 3 log10, and viral DNA synthesis by 32-fold.

[ii] Arvouet – Grand,A., Lejeune,B., Bastide,P., Pourrat,A., Privat,A.M., Legret,P. (1993) – Propolis extract. II. Wound healing the rat and rabbit (abstract),
in J. Pharm. Belg., May-June; 48(3), pp.171-78.

This work is related to wounds healing properties of a propolis extract. In first study on the Albinos Rabbit, the activity of a propolis extract is compared with these of a Peru balsam. Optimal concentrations of them in ointments are evaluated by applications on deep cutaneous scarifications. In order to go further into details, we have chosen in second part, another assay on the Rat, allowing the obtainment of deeper wounds. By this way, more complete quantification of retained parameters and a better appraising of the wounds healing process evolution are possible.

[iii] Baikowa, R.A., Terjochowa, N.W. (1978) – Experience obtained in the treatment of recurrent aphthous stomatitis (author’s transl),
in Zahn Mund Kieferheilkd Zentralbl, 66(5), pp.470-73.

Three different methods employed within the framework of complex therapy were used to treat 195 patients with recurrent aphthous stomatitis: 1. Alternative therapy using

prodigiosan, a bacterial polysaccaride. 2. Desensitizing treatment by using histaglobulin, an antihistaminic agent. 3. Symptomatic local treatment. The methods of treatment are described in detail. General therapy allowed the frequency of relapses and the duration of disease to be reduced and shortened, respectively. The use of a complex form of therapy is recommended.

[iv] Bankova V., Boudourova-Krasteva G. and Popov, S. are from Bulgaria (Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria. Kujumgiev Atanas is from the Bulgarian Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.

[v] Sforcin Jose and Maimoni-Rodella are from Brazil (Instituto de Biociencias, UNESP 18618-000, Botucatu, Sao Paulo State, Brazil).

[vi] Frete Xavier is from France but works in various countries (Bulgaria, Russia).

[vii] Basnet, P.; Matsushige, K.; Hase, K.; Kadota, S.; Namba, T. (1996) (Japan) – Potent antihepatotoxic activity of dicaffeoyl quinic acids from propolis,
in Biol Pharm Bull., Apr;19(4), pp.655-7.

Authors address: Research Institute for Wakan-Yaku (Traditional Sino-Japanese Medicines), Toyama Medicine and Pharmaceutical University, Japan.

Hepatoprotective activity guided chemical analyses led to the isolation of two dicaffeoyl quinic acid derivatives, methyl 3,4-di-O-caffeoyl quinate (1) and 3,4-di-O-caffeoyl quinic acid (2) from water extract of propolis, and their structures were determined by the use of 2D NMR. These compounds were stronger antihepatotoxic agents than glycyrrhizin.
PMID: 9132180, UI: 97014146.

[viii] Basnet, P.; Matsushige, K.; Hase, K.; Kadota, S.; Namba, T. (1996) (Japan) – Four di-O-caffeoyl quinic acid derivatives from propolis. Potent hepatoprotective activity in experimental liver injury models,
in Biol Pharm Bull., Nov;19(11), pp.1479-84 (***).

Authors address: Research Institute for Wakan-Yaku (Traditional Sino-Japanese Medicines), Toyama Medical and Pharmaceutical University, Japan.

The water extract of propolis (PWE) showed a strong hepatoprotective activity against CCl4-toxicity in rats and D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. The PWE also showed a significant hepatoprotective activity against CCl4-induced liver cell injury in cultured rat hepatocytes. The in vitro hepatoprotective activity guided fractionation and chemical analysis led to the isolation of four dicaffeoyl quinic acid derivatives from the PWE. The structure of these isolates was determined to be methyl 3,4-di-O-caffeoyl quinate (1), 3,4-di-O-caffeoyl quinic acid (2), methyl 4,5-di-O-caffeoyl quinate (3), and 3,5-di-O-caffeoyl quinic acid (4) by spectroscopic methods. These compounds were more potent hepatoprotective agents than glycyrrhizin at a concentration of 10 micrograms/ml and 1 was the most potent among the four compounds in the cultured hepatocytes. Quinic acid (5) alone did not show hepatoprotective effects in cultured rat hepatocytes against CCl4-toxicity. On the other hand, chlorogenic acid (6) or caffeic acid alone was found to be less potent than the dicaffeoyl quinic acid derivatives.
PMID: 8951168, UI: 97108847.

[ix] Basnet, P.; Matsuno, T.; Neidlein, R. (1997) – Potent free radical scavenging activity of propol isolated from Brazilian propolis,
in Z Naturforsch [C], Nov-Dec;52(11-12), pp.828-33.

Address: Pharmazeutisch-Chemisches Institut, Universitat Heidelberg, Germany.

We evaluated free radical scavenging activity of the water, methanol and chloroform extracts of propolis in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and xanthine-xanthine oxidase (XOD) generated superoxide anion assay systems. The free radical scavenging activity guided fractionation and chemical analysis led to the isolation of a new compound, propol (3-[4-hydroxy-3-(3-oxo-but-1-enyl)-phenyl]-acrylic acid) from the water extract, which was more potent than most common antioxidants such as vitamin C and vitamin E (alpha-tocopherol) in these assay systems.
PMID: 9463940, UI: 98125101.

[x] ANTIMETASTATIC ACTIVITY OF PROPOLIS, CAFFEIC ACID PHENETHYL ESTER AND CAFFEIC ACID AGAINST MAMMARY CARCINOMA OF CBA MICE

I. BASIC, N. ORSOLIC, A. BRBOT-SARANOVIC, Z. TADIC,
D. SULIMANOVIC

(CROATIA)

We have studied the antimetastatic efficacy of caffeic acid phenethyl ester (CAPE), a propolis-derived compound and compared it with the antimetastatic effect of either water-soluble derivatives of propolis (WSDP) or caffeic acid (CA). The tumor was a transplantable mammary carcinoma (MCA) of spontaneous origin, weakly immunogenic, to a syngeneic CBA mouse. Metastases in the lung were generated by injecting 2 x 10⁵ viable tumor cells intravenously. Tested compounds were given per os before or after tumor cell inoculation, the dose comprises 12.5 mg/mouse of either CAPE or CA, and 50 mg/mouse of WSDP, respectively. Both the preventive and the curative therapy significantly reduced the number of tumor nodules in the lung of mice. The antimetastatic effectiveness of both WSDP and CAPE was equally high and also higher than that of CA. Two approaches for testing the possible mode of antimetastatic activity in the lungs were proposed: a modulation of immune reaction of recipients or an induction of apoptosis during the formation of metastatic nodules. Changes in several immunological parameters, such as the response of lymphocytes to polyclonal mitogens in vitro, the production of tumor necrosis factor (a (TNF a) by lymphoid cells in vitro and the rosette formation of lymphoid cells with SRBC, correlated well with the antimetastatic properties of the tested compounds. A direct relationship was also found between the antimetastatic activity of the compounds studied and the induction of apoptosis.

p.119

[xi] Kittharz – die antibiotische Alternative

von Walter Binder (Naturheilpraxis 5/79)

Das Kittharz der Bienen hat nach Auffassung zahlreicher Forscher in aller Welt, insbesondere in Rumänien, der UdSSR, den USA und in Dänemark eine hervorragende antibiotische Wirkung. Eine stattliche Kasuistik untermauert diese Meinung Zunächst muß festgestellt werden, daß die Lebensform Biene, so wie sie heute in Erscheinung tritt, seit 42 Millionen Jahren existiert und eine abgrundtiefe Zahl anderer Insektenformen überlebt hat. Das hat sicher seinen Grund. Die ihr zugedachte Rolle, einmal die Bestäubung der Blüten, zum anderen die Verbreitung verschiedenster Pflanzensamen, hat ja auf die Pflanzenwelt eine mutagen-dynamisierende Wirkung und hilft ihren Bestand sichern.

Wenn eine bestimmte Tierart in unserer Biosphäre überlebt, dann muß ihr Organismus eine Reihe von wirksamen Programmen haben, die im Notfall rechtzeitig einsetzen. Unter den entscheidenden Eigenschaften ist wohl die wichtigste jene, wirksame Abwehrmechanismen gegen Mikro- wie auch Makro-aggressoren zu besitzen. Gerade diese Eigenschaften, eine universelle bakterizide und eine bakteriostatische Sekretproduktion, besitzen die Bienen. Daß z. B. in einem Bienenkorb von, Kubikmeter Volumen, ohne endemische Einbrüche 50.000 bis 60.000 Insekten auf engsten Raum und unter feuchttropischen Klima existieren, erscheint wie ein Wunder. Deshalb ist es auch einleuchtend, daß alle Produkte, die mit dem Speichel der Biene verarbeitet werden, von Bakterien, Viren und Pilzen nicht angegriffen werden können.

Den-Kittharz (auch Propolis genannt) besorgen die Kittharzbienen im Spätsommer und Herbst (August bis Oktober), wenn durch starke Sonneneinstrahlung.die Bäume harzen und das Harz flüssig genug ist für den Transport. Die Harzpartikel werden mit dem enzymreichen Speichel löslich gemacht und in den Kitthöschen deponiert. Im Stock übernehmen andere Arbeitsbienen den Kittharz, speicheiln ihn erneut ein und verschließen damit alle Ritzen und Spalten in der Stockwandung. Auch das Flugloch wird mit Kittharz eingefaßt. Es kommt den Bienen darauf an, sich für die kommenden Wintermonate vor Feuchtigkeit, Kälte, Zugluft, und, was das allerwichtigste ist, vor Mikro- und Makroorganismen zu schützen.

Unter anderem verwenden die Bienen den Kittharz auch zur Mumifizierung größerer Tiere, die nicht mehr aus dem Stock entfernt werden können, z.-B. kleine Eidechsen, größere Käfer usw. Der Kittharz hat eine hervorragende konservierende Wirkung, und verhindert die bakterielle Zersetzung. Befallen verschiedene Mikroorganismen z. B. der Pilz Aspergillus flavus die Bienenbrut, so werden die Pilzverseuchten Strecklarven sofort mit Kittharz bedeckt und damit auch die resistenten Sporen unschädlich gemacht.

Ersatz für Penicillin

Nun zum medizinischen Teil : Mikrobiologische Untersuchungen mit Tuberkelbazillen wurden bereits in Dänemark (1948 ) gemacht. Dabei hat sich ein wäßriger Extrakt aus Propolis gegen die an sich resistenten Bakterien als wirksam erwiesen. Später wurden erstmals an der TU in Kopenhagen Propolisextrakte an 30 verschiedenen Mikroorganismen angewandt und eine wachstumshemmende Wirkung beobachtet. 1968 untersuchten die dänischen Forscher Jens Hoiriis Nielsen und Hans Erik Christensen die Wirksamkeit von äthanolischen Propolisauszug gegen Schmarotzerpilze. Das Ergebnis verlief für alle Pilze tödlich. In einem Parallelversuch wurden 15 Propolisproben gegen 39 Bakterienstämme und 20 Schmarotzerpilzen angewandt. Davon wurden 24 Bakterienstämme in ihrem Wachstum gehemmt und alle 20 Pilzarten getötet. Die rumänischen Wissenschaftler. A. Derevici und A. Popesku fanden heraus, daß-Propolisextrakte auf Enterococcen eine absolut tödliche Wirkung haben, jedoch nicht auf Staphylococcen. Am staatlichen Forschungsinstitut für Medizin in Kazan (UdSSR) (1963) wurden 50 Tuberkulosepatienten mit einer propolishaltigen Ernährung kurmäßig versorgt. Das Resultat war außerordentlich zufriedenstellend. Todorov, ein bekannter bulgarischer Wissenschaftler, entdeckte die günstige Wirkung von Propolisextrakt auf das vegetative Nervensystem und beobachtete eine Gefäßerweiterung im mittleren Arterienbereich. Das wissenschaftliche Institut für Röntgenologie, Radiologie und Onkologie in Kiew (UdSSR) hat nach Strahlenverbrennungen die Haut mit Propolissalben erfolgreich behandeln können. Am staatlichen Laboratorium in Baschkirien (UdSSR) veröffentlichte der Wissenschaftler Tjeannitsjev einen profunden Bericht über die spezifischen Eigenschaften des Propolis gegenüber der Abwehr und wies auch eine hämatogene Wirkung nach. Seine Forschungsergebnisse belegte er mit 2000 Versuchen an Patienten.

Nach seiner statistischen Studien der Kasuistik sind die größten Erfolge bei Infektionen des Nasen-Rachenraumes zu verzeichnen. Es folgen Rhinitis, Sinusitis, Otitis media, Conjunktivitis, verschiedene Influenzaformen, unklare grippöse Infekte mit bronchitischer, Tendenz, Pyelonephritis, Cystitis, Prostatitis, Colitis, alle Enteritiden, Gastritis, Ulcus Duodenum sowie Magengeschwüre.

Extern: Ekzeme vor allem Mykosen, Ulcus cruris, nekrotische Gewebsprozesse, Brand, Karbunkel, und auch Phlegmonöse Entartungen.

Es läßt sich ohne Übertreibung sagen, daß Propolis die allmählich stumpf werdende Penicillinwaffe ersetzen könnte. Vor allem die einmaligen Ergebnisse von Z. G. Tjeannitsjev geben zu denken. Er hebt im besonderen hervor, daß die Phagozytenzahl merklich ansteigt, die Emigrationsgeschwindigkeit der Leukozyten beträchtlich zunimmt und im serologischen Test die Antikörper erhöht waren. Ihre Reaktionsgeschwindigkeit mit dem Antigen scheint vergrößert. Außerdem sein die fibrinolytischen Faktoren vermehrt und die roten Blutkörperchen zahlreicher. Er konnte auch an Hand seiner Kasuistik nachweisen, daß die Zahl der Koagulopathien spürbar sank.

Resümee: Die Wirkung.von Kittharz und seine komplexe Einflußnahme auf den Organismus ist um so rätselhafter, wenn man die chemische Inhaltsanalyse dazu vergleicht: 55 % Harz und Balsam, 30% Wachs, 10% flüchtige Öle, 5% Pollen, und als mineralische Verbrennungsrückstände: Calcium, Aluminium, Vanadium, Mangan und Silicium.

Einerseits scheint es auf das erythropoetische System eine gewisse Anstoßwirkung zu haben, das gesamte RES zu aktivieren, die fibrinolytische Entstehung in der Leber und seine hämatogene Entfaltung zu begünstigen, auf die Bakterienbesiedelung des enteralen Abschnittes selektpositiv einzuwirken, andererseits den adrenerg bedingten Hochdruck im mittleren Arterienbereich und Arteriolensystem durch sympathatikolytische Einflüsse zu senken. Fraglich ist auch eine anabol-hormonale Wirkung. Extern fördert Propolis die Granulierung und Epithelisierung von Wunden, Ekzemen und gutartigen Hautentartungen.

[xii] Brehm Reinhold Addresse: Postfach 1163, 96002 Bamberg. Tel. 0951-45194. Fax 0951-45581.

[xiii] BIENENPRODUKTE – V E R M A R K T U N G

Propolis,

ein Dauerbrenner!

Tatsächliche, rechtliche, künftige Vermarktungssituation

“Propolis, ein Bienenprodukt, das sich ständig steigender Nachfrage erfreut”. Unter diesem Titel beschrieb Herr VÖLKER, der, sich selbst als Hobbyimker bezeichnete, im Imkerfreund, Ausgabe 12/96, pp. 9/10, die aktuellen Vermarktungsmöglichkeiten von Propolisprodukten, vermittelte sein Knowhow, gab detaillierte Tips und Anregungen und als Zugabe noch eine Infoschrift zur Weiterverbreitung an Kunden. Wenn man seinen Ausführungen Glauben schenkt, hat sich ohne sein Zutun, Propolis als “Selbstläufer” herausgestellt und seine von der Wirkung begeisterten Kunden drängten ihn zum Verkauf dieses “Wundermittels”. Das einzige, das seine Kunden zusätzlich anregte, sei eine Informationsschrift, in der unter anderem Anwendungsmöglichkeiten beschrieben werden. Wer diesen Artikel liest, gewinnt zwangsläufig den Eindruck, daß die beschriebene Art der Herstellung, des Vertriebs und der Werbung, rechtens und zulässig sei. Dem ist jedoch nicht so! Summa summarum könnte der Artikel als Anleitung zur unsachgemäßen Herstellung eines Arzneimittels und dessenvertriebs angesehen werden.

Herr BRANDT aus Germering hat in der Ausgabe des IF 1/97, pp. 9, dargelegt, daß grundsätzlich das Inverkehrbringen von Propolis verboten sei. Er warnte, aus leidvoller Erfahrung, vor einem Verkauf unter der Hand, erklärte sich aber mit den Ausführungen des Herrn VÖLKER konform und suchte ungerechterweise die Schuld bei angeblich neidvollen Imkerkollegen. Eine wohl doppelbödige Moralvorstellung.

Beide Veröffentlichungen sind bereits vom Ansatz her falsch, denn es ist, bei dieser pauschalen Bewertung, weder erlaubt, noch grundsätzlich verboten, Propolisprodukte zu verkaufen! Die Veröffentlichungen und andere Verlautbarungen führen bei den Lesern zur totalen Verwirrung. Die meisten Imker, die Interesse an der Vermarktung von Propolisprodukten haben, sind ver-

4 IMKERFREUND 5 9 97

ständlicherweise verunsichert und wissen Oberhaupt nicht mehr, wie sie sich verhalten sollen.

Die häufigen Anfragen meiner Kunden, seit der Veröffentlichung vorgenannter Beiträge, zeigen einerseits, daß ein beträchtliches Interesse am Vertrieb von Propolispräparaten vorhanden ist, andererseits, daß ein dringender Aufklärungsbedarf besteht. Grund für mich, durch diesen Beitrag zu versuchen, etwas Klarheit zu schaffen. Mir geht es nicht darum, nun auch noch meinen “Senf” dazuzugeben, sondern den an der Vermarktungsfront stehenden Imkern, die rechtlich zulässige Situation zu erklären.

Eine nicht leichte Zielsetzung, denn dieses brisante Thema ist sehr komplex und Bewertungen müssen immer differenziert, stets auf den Einzelfall bezogen, erfolgen. Insoweit kann es auch nur um die Abhandlung von Grundsatzfragen gehen, deren Beantwortung, so hoffe ich, dem einzelnen Imker als Ausgangsbasis dienen soll.

Verwirrung und Verunsicherung

durch Falschinformation

Viele Imker, die sich auf das Wissen inkompetender Multiplikatoren verlassen haben, waren die Verlierer. Sie haben für eine angeblich gute Sache, oft in Unkenntnis der tatsächlichen rechtlichen Situation, letztlich doch leichtfertig gegen bestehende Vorschriften verstoßen. Behördlicherseits wurde zwar häufig der weitere Vertrieb untersagt auch unter Androhung von Zwangsgeld – hinsichtlich dertatverfolgung wurde jedoch meistens großzügig verfahren. Nachwievor gilt aber der Rechtsgrundsatz: “Unwissenheit schützt vor Strafe nicht”.

Von zuständiger oder kompetenter pp. gab es bislang leider kaumveröffentlichungen, die geeignet sind, die tatsächlich, rechtlich zulässigen Verrnarktungsmöglichkeiten, in einer annähernd verständlichen Sprache zu erklären. Insbesonders wurde nicht eingehend genug, vor den Her-

stellungsrisiken und dem Vertrieb mit arzneimittelbezogenem Charakter oder Aufmachung gewarnt. Eigentlich wollte ich Rücksicht üben und niemanden einen “Schwarzen Peter” zuschieben oder gar jemanden in Pflicht undverantwortung nehmen. Denn für das Inverkehrbringen eines Produktes und dessen Zulässigkeit ist letztlich jeder selbst verantwortlich. Kein Imker kann erwarten, daß ihm sein Verein, seinverband, die Landesanstalt oder sonstige imkerliche Institutionen die Verantwortung, für ein von ihm gefertigtes Produkt abnehmen. Nach meinem Verständnis, und dem der Mehrzahl der Imker, bezüglich Sinn und Zweck dieser Institutionen, kann aber erwartet werden, daß im Rahmen der Kompetenz und der fachlichen Zuständigkeit, sachlich fundierte und verlässliche Antworten auf Fragen gegeben werden, auf die der Imker vertrauen kann.

Gerade beivermarktungsproblemen (Propolisthematik), die die Imkerschaft seit Jahren bewegen und bei der die Rechtslage letztlich unverändert ist, werden mit Recht zutreffende, sachlich und juristisch richtige Aussagen erwartet. Liegt es am finanziellen Rahmen oder an Leichtfertigkeit, wenn z. B. ein Merkblatt verbreitet wird, in dem, gerade in den Kernpunkten, sachlich falsche Feststellungen getroffen werden? Wo wäre zum Beispiel die Industrie, wenn sie bei der Einführung eines noch nicht marktgängigen Produktes, sich nicht, durch ein für sie geeignetes Produkt- und Rechtsgutachten, die Verkehrsfähigkeit bescheinigen ließe? Gerade die Grundsatzfrage, ob und unter welchen Voraussetzungen Propolisprodukte verkehrsfähig sind, wäre auch unter Berücksichtigung der Kosten von den staatlichen Bieneninstitutionen zu klären gewesen. Der einzelne Imker kann sich in der Regel die Kostenbelastung dafür nicht leisten und kaum einer ist rechtlich versiert, sich durch den Dschungel der Vorschriften und bürokratischen Auslegungen zu schlagen.

Das von der Bayerischen Landesanstalt für Bienenzucht verbreitete Merkblatt (Prop. TXT/M/96), über Propolis, ist ein Beispiel dafür, wie durch Unsachlichkeit und rechtliche Unkenntnis, die Imkerschaft fehlinformier-t und dadurch verunsichert wird.

Das Institut stellt fest:

Ziff. 4 … nach derzeitiger RechtsAuffassung sind Propolis-Bereitungen als Fertigarzneimittel einzustufen, die entsprechend dem AMG einer Zulassung bedürfen. Hierzu liegen bereits Gerichtsentscheidungen vor …

Klarstellung: Die zitierten Gerichtsurteile geben diese pauschale, in der Sache unrichtige Behauptung nicht wieder. Die Urteile beziehen sich immer auf Einzelfälle und nicht auf Propoliszubereitungen insgesamt. Unter dem Begriff Zubereitungen würden alle mit Propoliswirkstoff versehenen Produkte fallen, auch Kosmetika. Da Kosmetika jedoch zulässig sind, widerspricht diese Aussage der Logik und der tatsächlichen, rechtlichen Gegebenheit.

Ziff. 4.1 Gewinnung und Verkauf von Rohpropolis: keine Beschränkung

Klarstellung: Gewinnung ist auf jeden Fall zulässig. Der Verkauf mit arzneilicher Zweckbestimmung oder Werbung (z. B. zur Einnahme) ist verboten, da Arzneimittel.

Ziff. 4.2 Herstellung von Propolistinktur: … Propolistinktur gilt als Fertigarzneimittel und darf für den Verkauf nur von Apotheken bzw. Personen mit vergleichbarer Ausbildung hergestellt werden.

Klarstellung: DasVerbot betrifft alle Propoliszubereitungen für arzneiliche Zwecke, denn es geht um die Herstellung von Arzneimitteln. Die Herstellung für kosmetische Zwecke, unterliegt nicht dieser Vorschrift, jedoch sind kosmetikrechtliche Normen und Bestimmungen zu beachten.

Ziff. 4.3 Verkauf von Propolistinktur: durch den Imker nicht zulässig. Verkauf allein durch den Apotheker als Einzelrezeptur zulässig.

Klarstellung: Diese Feststellung ist falsch. Propolistinkturen, mit kosmetischer Zweckbestimmung, die auch sonst in ihreraufmachung und Werbung, keine Merkmale eines Arzneimittels erkennen lassen, sind verkehrsfähig und dürfen auch von Imkern ohne irgendwelche Beschränkungen verkauft werden. Auch wenn der Erwerber, entgegen der kosmetischen Zweckbestimmung das Produkt für arzneiliche Zwecke kauft oder verwendet, wird

es im rechtllichen Sinne kein Arzneimittel. Beispiel: Kamilletee, der als Lebensmittel gekauft und für Erkrankungen verwendet wird.

Ziff. 4.5 Herstellung und Verkauf von Propoliscreme: als Kosmetikum darf Propoliscreme vom Imker hergestellt werden.

Klarstellung: Die Herstellung von Kosmetika richtet sich nach den Vorschriften des LMBG, KosV, Fertigpackungsverordnung, Maß- und GewichtsG und einer Reihe eingehender Richtlinien, in denen die Erfüllung bestimmter Mindestanforderungen, Normen, Qualitätsstandards und Qualifikation festgelegt ist. Die meisten kosmetischen Propolisprodukte, die einen Wirkstoffgehalt von ca. 1,6 % überschreiten, werden u. a. wegen der Gefahr sensibilisierender Wirkung (allergene Reaktionen) als Arzneimittel bewertet.

Zu beachten ist auch das Produkthaftungsgesetz. Demzufolge haftet der Hersteller, unabhängig eines Verschuldens, bis in Millionenhöhe, für sein Produkt. Bei einem nicht versichertem Imker, als Produzent kosmetischer Mittel, kann dies ein existenzielles Risiko darstellen.

Die angesprochene Standardzulassung, als vereinfachte Form einer Arzneimittelzulassung, wäre bei Propolistinktur, unter bestimmten Vorraussetzungen generell möglich, ähnlich wie bei Propoliskapseln. Das Produkt könnte dann freiverkäuflich als Arzneimittel, jedoch nur von Personen mit einer Erlaubnis nach § 50 AMG verkauft werden. Ein Ergebnis ohne viel imkerlichen Nutzen.

Zu Fehlauslegungen führen die unter Ziffer 3 aufgezählten Anwendungsmöglichkeiten, die vom Verfasser sicherlich nur als Aufzählung gesehen werden. Von Laien wird dies aber häufig als Hinweis dafür verstanden, daß die Produkte für die genannten Zwecke vertrieben werden dürfen. Ein ausdrücklicher Hinweis darauf, daß damit keine Verkehrsfähigkeit begründet werden kann, fehlt leider. Außerdem wurden bei imkerlichen Vorträgen und Schulungen, die Herstellungstechniken zwar eingehend beschrieben, rechtlich fundierte Aufklärung erfolgten aber kaum, obwohl die Absicht des Inverkehrbringens ersichtlich war.

Jeder Imker, ist im Rahmen, der ihm zumutbaren Sorgfaltspflicht, selbst verantwortlich. Er muß für Unbedenklichkeit, Zulässigkeit und die Art und Weise des Inverkehrbringens geradestehen. Leichtfertigkeit und blindes Vertrauen auf Aussagen, auch von Instituten, deren Namen eine besondere Gewichtigkeit haben, sind fehl am Platze. Verfasser, die sich befähigt fühlen, rechtliche Bewertungen abzugeben, sollten bedenken, daß der Leser ihren Worten glaubt und durch Falschmeldungen zu Fehlentscheidungen, die beträchtliche Folgen nachsichziehen können, verleitet wird. Besondere Sorgfalt und Objektivität ist deshalb angesagt. Durch die falschen Behauptungen, in dem über dievereine verbreiteten Merkblatt, wird nicht nur die Glaubwürdigkeit der Hersteller und Imker, die seit Jahren im rechtlich zulässigen Rahmen ihre Propolisprodukte vertreiben, in Frage gestellt, sondern die tatsächlich zulässigen Möglichkeiten verschleiert.

Die Verkehrsfähigkeit

eines Produktes

Von den Behörden kann grundsätzlich nicht erwartet werden, daß sie von sich aus, ein Produkt klassifizieren und dem Hersteller odervertreiberverkehrsfähigkeit bescheinigen oder ihn in seinem Sinne beraten. Sie werden meistens nur dann tätig, wenn offensichtlich gesetzlichevorschriften nicht beachtet werden. Dann besteht dieverpflichtung, das Produkt rechtlich zu bewerten und bei Beanstandung, erstens den Vertrieb zu untersagen, zweitens, hinsichtlich des erfülltentatbestandes, verfolgend zu wirken. Der Vertrieb von Propolisprodukten als Arzneimittel, ist keine Ordnungswidrigkeit, sondern eine Straftat. Insoweit ist es mir unverständlich, daß die Infoschrift des Herrn VÖLKER, als Vorlage zur Weiterverbreitung angeboten wurde. Die darin enthaltenen Anwendungsbeispiele haben überwiegend therapeutischen Nutzen und klassifizieren somit das Produkt als Arzneimittel. Für Nachahmer wäre einvertriebsverbot und Strafverfolgung die Folge.

Ich möchte dem Verfasser nicht unterstellen, daß er wider besseres Wissen, die Imker zu gesetzlich unzulässigem Handeln auffordern wollte. Gut gemeinte Ratschläge können jedoch bei so einem komplexen Thema leicht ins Gegenteil umschlagen, insbesondere dann, wenn der nicht so versierte Leser zur Nachahmung aufgefordert wird. Wenn der Eindruck entstände, die Imker setzten sich aus Profitgier über bestehende Vorschriften hinweg, die natürlich auch dem Verbraucherschutz dienen, wäre dies für das Image sehr negativ. Negativberichte hatten wir wahrlich genügend, auch wenn sie in den meisten Fällen unberechtigt warenSachkunde und Objektivität sind die Kritierien, die klare Aussagen und Vorgaben ermöglichen. Eine Orientierung am rechtlich zulässigen, nicht am wünschenwerten, ist zwingend nötig. Erfahrungsgemäß möchten die vernünftig denkenden und handelnden Imker, Rechtssicherheit beim Verkauf und nicht das Risiko derverfolgung. Nur dadurch wird der einzelne glaubhaft und kann langfristig einen zufriedenen Kundenkreis aufbauen, ohne befürchten zu müssen, daß ihm der Vertrieb untersagt wird und er die Folgen unrechtmäßigen Handelns zu tragen hat.

Durch die wiederkehrende Undifferenziertheit in der Diskussion um Propolis wurde eine Unsicherheit erzeugt, die u. a. zur Folge hat, daß die Imker, die rechtlich zulässige Propolispräparate verkaufen, von Imkerkollegen angegriffen werden und zu Unrecht vorgeworfen bekommen, der Verkauf sei nicht zulässig. Gleichzeitig müssen sich diese tatsächlich legal verhaltenden Imker, mit den Machenschaften derer auseinandersetzen, die illegal arzneimittelbezogen werben, die gesamte Imkerschaft inverruf bringen, die Behörden zu verstärkten Kontrollen veranlassen und sich dadurch noch einen Wettbewerbsvorteil verschaffen. Nicht die Imkerkollegen, auch wenn sie von einem Leserbriefschreiber als Denuntianten und Neider betitelt wurden, sind für “leidvolle Erfahrungen” (Anordnung auf Unterlassung unter Androhung von Zwangsgeld) verantwortlich, sondern die Anbieter selbst, die außerhalb von Recht und grdnung ihre Geschäfte tätigen. Uber Sinn und Zweck eines Gesetzes läßt sich stets streiten. Trotzdem muß akzeptiert werden, daß der Gesetzgeber diese Vorschrift erlassen hat, sie mittels Strafverfolgung und Zwangsmitteln durchsetzt und nicht, wie es einige gerne sehen würden, dem ungesetzlichen Treiben einiger Imker tatenlos zusieht. Seien wir doch froh darüber, daß uns unsere Bienen Stoffe zur Verfügung stellen, die wegen ihrer hohen Wirksamkeit, beim Kunden einen hohen Stellenwert haben. Die Vermarktung wird dadurch doch wesentlich begünstigt, ohne daß wir uns ins rechtliche Abseits begeben müssen.

Die Erwartungen des

Verbrauchers wirken sich aus

Daß die in der Propolis enthaltenen Wirkstoffe einen überaus günstigen Einfluß auf Krankheiten und Leiden haben, ist unbestritten. Dies begr-ündet auch die Feststellung des Herrn VÖLKER, daß sich Propolis als “Selbstläufer” entwickelt hat. Doch nicht alles, was gut ist und für die Volksgesundheit bedeutsam sein könnte, ist rechtlich erlaubt oder gibt das vermeintliche Recht, sich über Vorschriften hinwegzusetzen. Auch die häufige Argumentation, die Pharmaindustrie und die Apotheker seien aus wirtschaftlichen Gründen daran interessiert, daß Propolis nicht freiverkäuflich angeboten würde, ist unzutreffend. Einzig und allein das Arzneimittelgesetz (AMG), nach dessen Begriffsbestimmungen ein Stoff als Arzneimittel eingeordnet wird, ist hierfür verantwortlich. Das Gesetz stellt nicht auf die Wirkung oder den Nutzen eines Produktes ab, sondern trifft die Klassifizierung generell nach bestimmten Merkmalen, wie Verbrauchererwartung und Zweckbestimmung. Die sogenannte”Selbstläuferfunktion”, also die Erwartung des Verbrauchers, daß Propolis therapeutische Eigenschaften besitzt, wirkt sich in soweit negativ aus, daß das Produkt, wenn es nicht ausdrücklich für einen anderen Zweck bestimmt ist, im rechtlichen Sinne Arzneimittel wird und somit für den Imker nicht ohne weiteres verkehrsfähig ist. Die Diskussion, um eine Zulassung als freiverkäufliches Arzneimittel ist müßig, denn in der Folge, dürfte dieses nicht apothekenpflichtige Präparat, ähnlich wie Propoliskapseln, nur von Personen vertrieben werden, die eine in § 50 AMG geforderte Erlaubnis nachweisen können.

Diese Erlaubnis wird nur erteilt, wenn entsprechende Sachkunde (Lehrgang und Prüfung; Kosten ca. 800 DM) bescheinigt wird. Für den Imker eine Prozedur, die in der Regel nicht in Verhältnis zum Aufwand und Gewinn steht.

Als Arzneimittel, im Sinne des AMG, gelten Stoffe und Zubereitungen aus Stoffen, die dazu bestimmt sind, durch Anwendung am oder im menschlichen oder tierischen Körper, Krankheiten, Leiden, Körperschäden oder krankhafte Beschwerden zu heilen, zu lindern, zu verhüten oder zu erkennen. Unter Krankheit ist jede Störung der normalen Beschaffenheit oder der normalen Tätigkeit des Körpers zu verstehen, die geheilt oder gelindert werden kann.

Der Einfluß

der Zweckbestimmung

InseinemUrteilvom 11.05.1984 hat der Bayerische Verwaltungsgerichtshof entschieden, daß es keine “geborenen Heilpflanzen” gibt.

Pflanzen sind erst dann Arzneimittel, wenn sie eine entsprechende Zweckbestimmung erhalten haben. Die gesetzliche Festlegung des Arzneimittelbegriffs stellt nicht auf die objektive Eignung zu Heilzwecken ab, sondern verwendet das zum Subjektivieren tendierende Merkmal der Zweckbestimmung. Das heißt im Klartext. Pflanzen (auch pflanzliche Teile oder Stoffe von Pflanzen, wie Rohpropolis) sind grundsätzlich keine Arzneimittel im rechtlichen Sinn, auch wenn sie aufgrund ihrer Inhalts- oderwirkstoffe dazu geeignet sind, therapeutische Wirkungen zu erzielen.

Die Rohpropolis, die der Imker sammelt, ist also ein Grundstoff, der problemlos für die verschiedensten Zwecke, entweder in naturbelassener oder verarbeiteter Form, vertrieben werden darf. Hierbei kommt es nicht darauf an, ob die Rohpropolis zu Arzneimitteln, Kosmetik oder Lebensmitteln weiterverarbeitet werden soll. Die für die rechtliche Bewertung ausschlaggebende Zweckbestimmung erfolgt also erst auf einer späteren Verarbeitungsodervertriebsstufe.

Anders verhält es sich jedoch bei Rohpropolis, die direkt dem Endkunden angeboten wird. Hierbei ist es egal, ob die Ware aus eigener Gewinnung stammt oder zugekauft wurde. Diesem Produkt, das ausgänglich Grundstoff ist, wird

zwangsläufig durch das Anbieten für einen bestimmten Anwendungsbereich, eine Zweckbestimmung erteilt.

Propolisrohware oder -granulat, das unmittelbar zum Zwecke der Einnahme (z. B. durch Kauen) in den Verkehr gebracht wird, hat in der Regel als Zielrichtung, die körperliche Aufnahme, der in der Propolis enthaltenen Wirkstoffe. Da diese nicht überwiegend der Ernährung oder dem Genuß im Sinne des Lebensmittelbedarfgegenständege setzes (LMBG) dient, wegen des mangelnden Nähr- oder Genußwertes, muß bei objektiver Betrachtung angenommen werden, daß die Einnahme auf therapeutische Anwendungen abzielt. Somit hat der Stoff Arzneimittelcharakter und wird zum Arzneimittel, das nicht verkehrsfähig ist, weil es die notwendigen Voraussetzungen nach dem AMG nicht erfüllt.

Ein Inverkehrbringen zum Kauen, mit dem Zweck der Zahnfleisch-, Mund- und Rachenpflege, also zu rein kosmetischen Zwecken, ist zwar nicht auszuschließen, jedoch rechtlich umstritten.

Propoliszubereitungen (z. B.Tinkturen) und sonstige Erzeugnisse, die Propolis als Wirkstoff enthalten, müssen stets im Einzelfall hinsichtlich ihrer rechtlichen Einordnung geprüft und bewertet werden. Pauschale Aussagen sind nicht möglich. Die pauschalen Aussagen, die leider immer wieder bei Vorträgen und Diskussionen oder aufgrund von Veröffentlichungen erfolgen, bringen mehr Verwirrung als Klarheit. Es kann grundsätzlich nicht gesagt werden: Propolis ist ein Arzneimittel, ein Lebensmittel oder ein Kosmetikum. Auch kann das gleiche Produkt, bei unterschiedlicher Aufmachung, Deklarierung oder begleitender Werbung, eine rechtlich unterschiedliche Bewertung erfahren. Es kommt also nicht allein auf das Präparat oder dessen Zusammensetzung an, sondern auch auf eine Vielzahl anderer Bewertungsmerkmale. Maßgebliche Merkmale sind Name und Aufmachung, Werbung, Erscheinungsform, allgemeine Verkehrsauffassung, medizinische und pharmazeutischewissenschaft und Praxis und Verbrauchergewohnheiten.

Die rechtliche Bewertung

des Stoffes Propolis

Generell muß gesagt werden, daß sich in rechtlicher Hinsicht, gegenüber früher nichts geändert hat und sich in absehbarer Zeit nichts wesentliches ändern wird. Lediglich ist bei der rechtlichen Bewertung des Stoffes Propolis, insbesonders durch das viel zitierte Urteil des OVG Hamburg aus dem Jahre 1994, eine differenziertere Einordnung erfolgt.

In dem zur Verhandlung stehenden Verfahren ging es um

1. Propolis-Kapseln, zur Stärkung des Immunsystems,

Wirkstoffanteil: 100 mg/Kapsel

2. Propolis-Öl,gegenHämorrhoiden, zum Bepinseln von Krampfadern und Prellungen

Wirkstoffanteil: 6 % Propolisextrakt

3. Propolis-Salbe,zurPflegederHaut

Wirkstoffanteil: 10 % Propolisextrakt

4. Propolis-Tinktur, zur Stärkung der Abwehrkräfte

Wirkstoffanteil: 12 %. Propolisextrakt.

Das Gericht stellte fest, daß die genannten Propolisprodukte, Arzneimittel sind und für deren Herstellung undvertrieb eine Herstellungserlaubnis und eine Zulassung durch das Bundesgesundheitsamt erforderlich ist. Da eine Zulassung nicht vorlag, wurde das Verkehrsverbot bestätigt. Darüberhinaus verbot das Gericht einen weiteren Vertrieb der Produkte unter anderer Deklarierung (z. B. als Kosmetikum) mit der Begründung, daß die Verbrauchererwar-tung und die Zweckbestimmung aufgrund vorangegangener Werbung für dieses Produkt festgelegt sei und die Verbraucher, auch bei anderer Bezeichnung, das Produkt für den vorherigen Zweck kaufen würden. Diese sogenannte “Selbstläuferwirkung”, die auch Herr VÖLKER beschrieb, ist nichts anderes, als die vom Gericht zu Recht erkannte Erwartung, daß Propolis vorrangig für Heilzwecke gekauft wird. Dies ist einerseits ein Verkaufsvorteil, andererseits aber ein enormer Nachteil, weil durch diese entstandene Verbrauchererwartung, dervertrieb von Propolisprodukten erschwert wurde.

Der Einfluß der Dosierung

Für die Einordnung als Arzneimittel spricht eindeutig bei den Artikeln 1, 2 und 4, daß sie sich in ihrer Zweckbestimmung auf therapeutische Anwendungen beziehen, also Erkrankungen vorbeugen, lindern oder heilen sollen.

Die Propoliscreme stufte das Gericht ebenso ein, obwohl dieses Produkt zur Hautpflege deklariert war. Ausschlaggebend war hierbei, der hohe Wirkstoffanteil von 10 %, der für Kosmetika unüblich ist und deshalb für arzneiliche Anwendung spricht.

Dies war auch ein wesentliches Kriterium bei der Beurteilung des Propolis-Öles mit einem Wirkstoffanteil von 6 %. Generell muß davon ausgegangen werden, daß bei Überschreitung der im kosmetischen Bereich üblichen Dosierungsgrößen und bei einem Mißverhältnis zwischen Wirkstoffmenge und Wirkungseffekt, trotz Deklarierung als Kosmetikum, eine versteckter Arzneimittelvertrieb gesehen wird und eine Einordnung als Arzneimittel erfolgt. Bei den üblichen Dosierungsmengen stützte sich das Gericht nicht auf vergleichbare Imker-

8 IMKERFREUND 5 9 97

produkte, sondern legte die Werte des Industrieverbandes für Körperpflege und Waschmittel e. V. zugrunde.

Das Urteil ist zwar kein Grundsatzurteil in Sachen Propolis. Es hat jedoch im Kernsatz rechtliche Einordnungen diesbezüglich vorgenommen, die im Gleichklang mit anderen Rechtsauffassungen und Kommentaren stehen. Insoweit wird das Urteil künftig von Bedeutung sein bei der Bewertung eines Propolisproduktes als Arzneimittel, Lebensmittel oder Kosmetikum. Als grundsätzlich festgeschriebene Kriterien müssen beachtet werden: a) Nach allgemeiner Verkehrsauffassung ist Propolis ein Stoff mit arzneilichen Eigenschaften und wird aufgrund der Verbrauchergewohnheiten überwiegend als solcher verwendet. Propolis ist heute so bekannt, daß auch ohne Werbung oder Deklarierung, das Produkt als Naturheilmittel gekauft wird. In der Praxis bedeutet dies, daß z. B. die alleinige Bezeichnung: “Propolis”, “Propolis-Tinktur” etc. für die Annahme als Arzneimittel spricht. Ebenso sind Einnahmeempfehlungen (z. B. täglich soundso viel Tropfen) eindeutig eine arzneiliche Aussage (innerliche Anwendung), weil nach Art des Stoffes Propolis nicht zum Zwecke der Ernährung oder des Genusses angesehen wird. b) Die Abgrenzung zwischen Arzneimitteln und Kosmetika ist ebenfalls nach allgemeinerverkehrsauffassung vorzunehmen. Allerdings verlieren kosmetische Mittel nur dann ihre Eigenschaft als solche, wenn sie überwiegend dazu bestimmt sind, Arzneimitteleigenschaften zu haben. Als Indiz dafür, daß äußerlich anzuwendende Produkte überwiegend für andere als kosmetische Zwecke dienen, ist heranzuziehen, daß überwiegend auf die Bezeichnung Propolis, dessen antibakterielle oder sonstige pharmazeutische Wirkung oder einen besonderen Wirkstoffgehalt, abgestellt wird. Bei der Herstellung von Hautpflegepräparaten liegt die Dosierungsmenge in der Regel unter 1,6 %. Dosierungen darüber, werden also als Hinweis gesehen, daß das Produkt anderen als kosmetischen Zwecken dienen soll. Bei Propolistinkturen als Pflegemittel für den Mund- und Rachenraum, über 10 % Wirkstoffgehalt, gilt ähnliches. Hinzukommt, daß hochdosierte, somit dickflüssige Lösungen, wegen negativer Begleiterscheinungen, weniger gut für die Anwendung geeignet sind.

c) Der Vertrieb von Propolistinkturen mit sehr hohem Wirkstoffanteil

(z.B. 50 % und mehr), kann von den vorgenannten Bewertungskriterien im Einzelfall abweichen, wenn es sich um Grund- oder Ausgangsstoffe zur Herstellung von kosmetischen Zubereitungen oder Zubereitungen im Lebensmittelbereich handelt. Wichtigster Ausgangspunkt ist auch hier die Zweckbestimmung. Genauso wie andere Wirkstoffe kann auch in diesem Bereich, Propolis, unabhängig seiner therapeutischen Eigenschaften, in entprechender Aufmachung und Deklarierung vertrieben werden. In der Regel handelt es sich hierbei jedoch um einen Vertrieb zwischen Extrakthersteller und dem Hersteller eines kosmetischen Produktes oder eines Herstellers von Lebensmitteln (z. B. Imker-Propolis-Honig). Im Einzelfall kann der Abnehmer aber auch ein Endkunde sein, der sich selbst Kosmetikzubereitungen herstellt und den Stoff als Wirkstoff hierfür bezieht.

Propolis als

kosmetisches Mittel

Grundsätzlich muß davon ausgegangen werden, daß Propolisprodukte (ausgenommen Rohpropolis) als Arzneimittel angesehen werden, soweit sie nicht überwiegend kosmetischen Zwecken dienen. Kosmetische Mittel sind Stoffe und Zubereitungen aus Stoffen, die dazu bestimmt sind, äußerlich am Menschen oder in seiner Mundhöhle zur Reinigung, Pflege oder zur Beeinflussung des Aussehens oder des Körpergeruchs angewendet zu werden.

Der Begriff der kosmetischen Mittel setzt also äußerliche Anwendung oder die im Munde voraus. Im konkreten Fall bedeutet dies, daß Propolistinktur beispielsweise zur Mundspülung, zwecks Mund- und Rachenpflege oder vorbeugend gegen Zahnfleischbluten, vertrieben werden darf. Propolistinkturen, in entsprechender Aufmachung und Deklarierung, können weiterhin als Kosmetikum vertrieben werden. Selbstverständlich müssen hierbei die übrigen kosmetikrechtlichen Bestimmungen erfüllt sein.

Rechtlich unerheblich ist es, was der Kunde mit dem Produkt macht.Verwendet er es z. B. zur Einnahme, verändert sich der rechtliche Charakter nicht. Es bleibt ein Kosmetikum, obwohl es als Arznei verwendet wird. Zur Verdeutlichung möchte ich den Kamilletee und den Kamillearzneitee anführen. Beide Produkte können in der Zusammensetzung identisch sein. Während der Kamilletee ein Lebensmittel ist – zur Herstellung eines wohlschmeckenden Getränkes – und unbegrenzt verkauft werden kann, ist der Arzneitee ein freiverkäufliches Arzneimittel bei entzündlichen Erkankungen und unterliegt der Verkaufsbeschränkung (Erlaubnis) nach dem AMG. Verwendet der Käufer den Arzneitee als wohlschmeckendes Getränk, bleibt das Produkt ein Arzneimittel.Verwendet er den”normalen” Kamilletee zu Arzneizwecken, bleibt er trotzdem ein Lebensmittel. Eine veränderte Zweckverwendung durch den Kunden, hat keinen unmittelbaren Einfluß auf die vorherige rechtliche Bewertung. Dies kann in der Praxis, gerade bei Propolis von Bedeutung sein.

Vorsicht ist geboten, wenn begleitende Schriften mit Einnahmeempfehlungen oder Anwendungsvorschlägen, egal ob sie einen Bezug auf das Produkt nehmen oder nicht, in unmittelbarem Zusammenhang (z. B. am gleichen Verkaufsstand) mit Propolisprodukten angeboten werden. Dies könnte als eine mittelbare Werbung ausgelegt werden. Auch nach kosmetikrechtlichen Vorschriften besteht einverbot der gesundheitsbezogenen Werbung. Problematisch wird es für diejenigen, die bisher ein Produkt verkauften, das aufgrund seiner Aufmachung oder Werbung als Arzneimittel anzusehen ist. Durch eine bloße Änderung des Etiketts, ändert sich nicht gleich die rechtliche Bewertung. Denn durch den bisherigen Verkauf hat sich eine Zweckbestimmung gebildet, die auf das geänderte Produkt weiter wirkt.

Wiederverkaufsware

Selbstabfüller, die sogenannte Bulkware (Ware zur Weiterverarbeitung, die nicht direkt für den Endverkauf bestimmt ist) beziehen oder Propolistinkturen in Endverkaufspackungen ohne Etikett, sollten besonders vorsichtig sein, auch

wenn ihnen eine sogenannte Verkehrsbescheinigungen angeboten wird, denn es kommt nicht allein auf den Stoff als solchen an, sondern viel mehr auf die Art der Aufmachung, Deklarierung und Werbung. Die rechtliche Verantwortlichkeit liegt hierbei in erster Linie nicht beim Händler, sondern beim Imker, der durch das Abfüllen oder Etikettieren derverbrauchspackung (Fertigpackung), in die Pflicht genommen wird. Eine Fertigpackung muß eine Reihe rechtlicher Vorschriften erfüllen. Es müssen Angaben über Hersteller odervertreiber, Mengenangabe, Chargennummer, Kennzeichnung der Inhaltsstoffe nach INCI-Namen, Haltbarkeitsdatum, Angaben über Verwendungszweck vorhanden sein. Je mehr das Produkt auf hohen Harz- oder Wirkstoffanteil abzielt, desto leichter wird die Schwelle zum Arzneimittel überschritten. Zum Beispiel werden Propolislösungen mit 10 % Wirkstoffanteil als geeigneter für die Anwendung im Mundraum angesehen, als erheblich höher dosierte, die dazu neigen, zu verkleben und die Zähne zu verfärben. Weniger ist manchmal mehr und eine häufigere Anwendung kann bei Bedarf jederzeit vorgenommen werden.

Viel wichtiger als eine Verkehrsbescheinigung, die nichts anderes ausdrückt, als daß ein bestimmtes Produkt in einer bestimmten Zusammensetzung, Aufmachung und Deklarierung, verkehrsfähig im Sinne des LMBG/Kosmetik-VO ist, ist ein Service, wie ich es meinen Kunden anbiete: Musteretiketten, die inhaltlich von der Regierungsbehörde bereits geprüft und abgesegnet sind, zurverfügung zu stellen und im Zweifelsfall, den Imker, der verständlicherweise unter eigenem Namen das Produkt verkaufen möchte, sach- und fachkundig zu beraten. Nur so ist es dauerhaft und unproblematisch möglich (für den Lieferanten und den Imker), Propolisprodukte im rechtlich zulässigen Rahmen zu vertreiben. Rechtssicherheit ist wichtiger als momentane hohe Umsätze und darauffolgendes Verkehrsverbot.

In den nunmehr 12 Jahren, in denen wir unter anderen Propolisprodukte herstellen und verarbeiten, wurden verständlicherweise im Rahmen der üblichen Probeziehungen durch die Lebensmittelbehörden und Regierungen auch unsere Erzeugnisse überprüft. Trotz der strengen Auslegungen der Landesuntersuchungsämter bestätigte die zuständige Regierungsstelle – in Abstimmung mit dem Bayerischen Staatsministerium -jeweils dieverkehrsfähigkeit. Ein Zeichen dafür, daß Propolisprodukte, insbesondere Propolis-flüssig, nicht vom Markt verschwinden müssen, sondern im zulässigen, rechtlichen Bereich ihren Platz behaupten können.

Risiken der Herstellung

Gemäß den Leitlinien für kosmetische Mittel wird unter Ziffer 1.2 eine berufliche Qualifikation der für die Herstellung verantwortlicher Personen gefordert. Damit soll der unsachgemäßen Herstellung vorgebeugt werden. Imker, die Propolislösungen selbst herstellen, verfügen nicht über die geforderte Ausbildung im technischen und naturwissenschaftlichen Bereich und können sich somit nicht als qualifiziert betrachten. Ein sicherlich nicht unnötiger Beitrag zumverbraucherschutz, denn welcher Imker hat, abgesehen von der Qualifikation, die erforderlichen Einrichtungen und Analysegeräte um festzustellen, ob das von ihm gefertige Produkt den Anforderungen an Qualität, Reinheit und Rückstandsfreiheit entspricht. Gerade bei dem Naturstoff Propolis, können durch Umweltbelastung und unbeeinflußbare Schadstoffkonzentrationen (insbesondere Blei, Cadmium und Pflanzenschutzmittelrückstände) vorliegen, die die zulässige Norm bei weitem überschreiten.

Welcher Imker konnte denn tatsächlich ausschließen, daß in seiner gefertigtentinktur nicht mehr Schadstoffe waren, als positive Wirkstoffe. Unter diesem Aspekt muß auch einmal das Vorgehen der Behörden gesehen werden, die Propolisprodukte der Imker näher unter die Lupe zu nehmen. Wer nach dem Motto verfährt, der Zweck heiligt die Mittel, macht nicht nur sich unglaubwürdig, sondern bringt auch seine Imkerkollegen in Verruf. Der Kunde hat ein Anrecht auf ein sicheres Produkt.

Risiken der Vermarktung

Beim Verkauf von Propoliserzeugnissen auf Märkten ist zu beachten, daß unabhängig von der Verkehrsfähigkeit eines Produktes, nach geltendem Marktrecht, nur der Vertrieb bestimmter Waren zulässig ist. In der Praxis hat sich gezeigt, daß die Auslegung bezüglich der Warengruppen unterschiedlich gehandhabt wird. So hat zum Beispiel das Marktamt der Stadt München den Verkauf von Propoliserzeugnissen grundsätzlich untersagt, während auf anderen Märkten der Vertrieb (als Kosmetikum) gestattet oder geduldet wird. Diese Einschränkung hat aber nichts mit der Verkehrsfähigkeit des Produktes selbst zu tun.

Diejenigen, die neidvoll in unser Nachbarland Österreich schielen und die dortigen Imker, wegen der in ihrem Land noch gültigen Regelung beneiden, wonach Propolistinktur, nach Anmeldung, als Verzehrprodukt vertrieben werden darf, werden sicherlich in absehbarer Zeit feststellen, daß durch die Harmonisierung im EG-Recht und der Vereinbarung der Mitgliedsstaaten zur Angleichung des Arzneimittelrechtes, auch diese günstige Regelung aufgehoben wird. Entgegen deutschem Recht gibt es in Osterreich noch Verzehrprodukte, das sind Stoffe, die dazu bestimmt sind, von Menschen gegessen, gekaut oder getrunken zu werden, ohne überwiegend Ernährungs- oder Genußzwecken zu dienen oder Arzneimittel zu sein. Also eine begriffliche Erweiterung gegenüber dem deutschen Recht, in dem es früher eine ähnliche Regelung gab. Ausschlaggebend ist aber auch dort derverzicht auf arzneiliche Zweckbestimmung und Werbung. Ein in Österreich hergestelltes Präparat kann in Deutschland nur nach hier geltendem Recht vertrieben werden.

Imker, die meinen, sie könnten, zwecks ihrer Interessen, eine Änderung des Arzneimittelrechtes erreichen, werden nichts ausrichten.

Dafür wäre eine grundlegende Reform, für die kein ausreichendes politisches Interesse oder ein Handlungsbedarf besteht, erforderlich. Es kann nur derjenige etwas gewinnen, der sich auf die Gegebenheit und Realität einstellt und seinen rechtlich zulässigen Weg der Vermarktung findet und von vorneherein mögliche Stolpersteine umgeht.

IMKA-Naturprodukte Reinhold Brehm Postfach 11 63 96002 Bamberg

Tel.: 09 5114 51 94

Fax: 09 5114 55 81

[xiv] Brumfitt,W., Hamilton-Miller,J.M.T., Franklin,I. (1990) – Antibiotic activity of natural products: 1. Propolis (abstract),
in Microbios., 62(250), p.19-22.

Material extracted from propolis (bee glue) by alkaline aqueous solvents or organic solvents showed weak inhibitory activity in vitro against certain species of Gram-positive bacteria. No

antimicrobial activity was detected in urine from three volunteers who had taken 500 mg propolis three times a day for 3 days.

[xv] Food Chem Toxicol 1998 Apr;36(4):347-363

Review of the biological properties and toxicity of bee propolis.

Burdock GA

Burdock and Associates, Vero Beach, FL 32963, USA.

Propolis is a multifunctional material used by bees in the construction and maintenance of their hives. Use of propolis by humans has a long history, predated only by the discovery of honey. Use of products containing propolis have resulted in extensive dermal contact and it is now increasingly being used a dietary supplement. Unlike many ‘natural’ remedies, there is a substantive database on the biological activity and toxicity of propolis indicating it may have many antibiotic, antifungal, antiviral and antitumour properties, among other attributes. Although reports of allergic reactions are not uncommon, propolis is relatively non-toxic, with a no-effect level (NOEL) in a 90-mouse study of 1400 mg/kg body weight/day.

PMID: 9651052, UI: 98313072

[xvi] Facultad de Agronomía y Agroindustrias. Universidad Nacional de Santiago del Estero. Avda. Belgrano 1912. Sgo del Estero. República Argentina. Teléfono: 0381-4509528. Fax: 0381-4214499.

Email: llchaillou@latinmail.com // cedia@unse.edu.ar

[xvii] Abstract

La provincia de Santiago del Estero ocupa el sexto lugar dentro de las provincias productoras de miel, actualmente cuenta con 40.000 colmenas, la mayoría de las cuales se encuentran ubicadas en los departamentos Capital, Banda y Robles, considerando estas cifras y el aumento considerable de la demanda externa de propóleos tipificado, se hace necesario establecer las características del propóleos santiagueño.

El objetivo general de este trabajo de investigación fue evaluar las características físico-químicas del propóleos de la provincia. Para ello se tomaron muestras por raspado de los departamentos Capital, Banda y Robles.

Los propóleos analizados mediante pruebas sensoriales presentaron estructura homogénea, en trozos irregulares con brillo (41.18% de las muestras) y con poco brillo u opacos (29.41% para cada tipo). La consistencia fue dura para el 47.06% de las muestras, y poco blanda y blanda para el 35.29% y 17.65% de las muestras respectivamente. La coloración de los propóleos estudiados fue variada : marrón claro con tintes castaños (5.88%), marrón oscuro con tintes castaños (11.77%), marrón oscuro con tintes amarillos (5.88%) presentando la mayoría (76.74%) color marrón oscuro. Se detectó sabor picante en todas las muestras y el olor predominante fue resinoso aromático (58.82%).

Con respecto a las características físico-químicas y utilizando técnicas de extracción con solventes adecuados para cada componente, se determinó que el contenido de impurezas mecánicas osciló entre un mínimo de 9.98% y un máximo de 37.14%; el contenido de cera varió entre 17.04% y 49.08% y el de resinas entre 35.05% y 54.14%. La variación del índice de oxidación fue desde un mínimo de 3 hasta un máximo de 18 segundos.

Todas las muestras, sin excepción, presentaron reacción positiva a la presencia de flavonoides y con la técnica espectrofotométrica del cloruro de aluminio se determinó que el valor mínimo del contenido de dichos compuestos expresados como quercetina fue 0.23 %, correspondiendo un 2.02 % al valor máximo. Mediante la técnica espectrofotométrica que utiliza el reactivo de Folin Ciocalteus la concentración de los compuestos fenólicos, expresados como ácido gálico equivalente, osciló entre 4.25 % y 24.73 %.
Los resultados precedentes permiten concluir que los propóleos analizados son de buena calidad, destacándose el contenido de flavonoides, que permite clasificarlos como propóleos de tenor medio de estos compuestos.

[xviii] Chopra,S.; Pillai,K.K.; Husain,S.Z.; Giri,D.K. (1995) – Propolis protects against doxorubicin-induced myocardiopathy in rats,
in Exp Mol Pathol 62(3), pp.190-98 (***) .
Propolis (bee glue) is one of the major hive products of bees and is rich in flavonoids, which are known for antioxidant activities. Doxorubicin-induced myocardiopathy is the consequence of oxidative stress through the mediation of free radicals. The effect of intraperitoneal administration of propolis (50 and 100 mg/kg) was studied on cardiomyopathy produced by doxorubicin (10 mg/kg, i.v.) in rats. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), blood and tissue glutathione (GSH), and thiobarbituric acid reactive substances (TBARS) in heart were estimated to assess the status of heart muscle. An elevation of the levels of CK, AST, GSH, and TBARS was observed following doxorubicin treatment. Parallel experiments with a pretreatment of propolis significantly reduced the levels of these parameters . Biochemical observations were supplemented by histopathological examination of heart sections. The protective effect of propolis was compared with that of rutin, a known cardioprotective flavonoid. The study demonstrates the cardioprotective effect of propolis in doxorubicin-induced experimental cardiotoxicity.

[xix] Christov, R.; Bankova, V.; Hegazi, A. G.; Abd El Hady, F.K.; Popov, S. (1998) – Chemical Composition of Egyptian Propolis,
in Z. Naturforsch. 53 c, pp.197-200 (abstract).

A sample from Egyptian propolis was investigated by TLC and MC/MS. 39 compounds were identified, 8 being new for propolis. Partial structures of four new esters of caffeic acid have been proposed.

[xx] FORSCHUNGEN ZUR HERSTELLUNG EINES APITHERAPIE

ARZNEIMITTELS FÜR MAGEN- UND DARMLEIDEN

Magdalena CRAVCENCO
Olga STOICHITOIU (Romania)

Die Apitherapie, die die menschlichen Krankheiten mit Bienenprodukten heut, befaßt sich auch mit denen des Verdauungstrakts Im Forschungslabor des Apitherapie-Arzneizentrums von Bukarest studierten wir die Herstellung eines optimalen Arzneimittels mit standardisiertem Propolisextrakt spiss und einem Gesamtpollenextrakt. Dieses noch experimentelle Produkt testeten unsere Ärzte und erhielten positive Ergebnisse bei Krankheiten des Verdauungsapparats, wie Magen-geschwür, Zwölffingerdarmgeschwür, Magenentzündung, erhöhte Magensäure, Darmkrankheiten, funktionale Störungen der Leber und der Gallenwege.

S. 520

[xxi] de Castro, S. L.; Higashi, K. O. (1995) – Effect of different formulations of propolis on mice infected with Trypanosoma cruzi,
in J Ethnopharmacol, 46(1), pp.55-8 (***).

Propolis, a bee product, can be regarded as one of the potential natural sources in folk medicine, displaying strong antimicrobial activity. Previous work showed that propolis extracts exhibited in vitro activity against Trypanosoma cruzi (Higashi and de Castro, 1994). Different formulations of propolis were administered to experimentally Trypanosoma cruzi-infected mice and the parasitemia kinetics and survival rate were monitored. The oral administration of ethanolic extracts up to 1.2 g propolis/kg per day or propolis offered ad libitum in the drinking water (up to 4 g/kg per day) or added to the food (up to 5 g/kg per day) did not interfere with both parameters. The differences between in vitro and in vivo trypanocidal activity of propolis and future perspectives are discussed.

[xxii] Dimov, V.; Ivanovska, N.; Bankova Vassya; Popov, S. (1992) (Bulgaria) – Immunomodulatory action of propolis: IV. Prophylactic activity against gram-negative infections and adjutant effect of the water-soluble derivative,
in Vaccine 10(12), pp.817-23.

The efficacy of the water-soluble derivative (WSD) of natural propolis (bee glue) was examined for augmentation of host resistance against experimental infections caused by Gram-negative pathogens (Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa). The substance was found to induce significant non-specific protection, but did not inhibit the in vitro growth of the same strains. Pretreatment with WSD prior to the standard scheme for tumour necrosis factor (TNF) induction (BCG and two weeks later lipopolysaccharide (LPS) provoked an interval-dependent reduction in the lytic capacity of serum against L 929 target cells. The replacement of the triggering or priming signal with WSD markedly increased TNF production. In vivo administration of WSD led to a rapid and route-dependent change in the alternative complement pathway haemolysis. The alteration in C1q complement component and total protein synthesis, and also in nitroblue tetrazolium reduction, suggests that macrophage activation makes a major contribution to the capacity of WSD to prevent infections.

[xxiii] RHEOLOGIE DER PROPOLIS
L. DRAGANOVA
I. IVANOV (Bulgarie)

Wir studierten die Möglichkeit der Anwendung der rheologischen Parameter bei der Charakterisierung der Propolis. Anhand der modifizierten UPS XXI-Methode haben wir die rheologischen Parameter der reinen Propolis bestimmt Fließart, Penetranzindex und Grenzspannung des Gleitens. Es wurde festgestellt, daß die Propolis ein plastischer Körper mit einer bestimmten Grenzspannung des Gleitens ist.
S. 551

[xxiv] Drogovoz, S.M.; Tikhonov, A.I.; Slyshkov, V.V.; Sal’nikova, S. (1994) – The liver-protective properties of the pediatric drug form of propolis in animals of different age groups,
in Eksp Klin Farmakol, 57(4), pp.39-42 (***).

The pharmacological activity of a pediatric formulation of the phenolic hydrophobic drug propolis was studied in the experiments on albino rats of various age with toxic liver damages of various duration and in acute hepatic ischemia. In all models of hepatic abnormalities, the drug was found to show antioxidative properties which were moderate (30- 60%).

In addition, there were improvements in hepatic secretion of bile, cholic acids, and cholesterol. On the other hand, the membrane- stabilizing effect of the drug was exerted in not all the tested models of hepatic damage.

[xxv] Dumitrescu,M. (1992) (Romania) – The mechanisms of the antiherpetic action of aqueous propolis extracts I. The antioxidant action on human fibroblast cultures (abstract),
in Rev. Roum. Virol., Jul.-Dec., 43(3-4), pp.165-73 (***).

A redox state modulation model was worked out in human fibroblast cultures treated with oxidation stress inducing agents and a redox agent, virtually protecting cell against the stress. Quantification of the global redox changes in fibroblasts was done using the hemoglobin electronic spectrum, in the presence and in the absence of H2O2.

[xxvi] Dumitrescu, M.; Crisan, I.; Esanu, V. (1993) (Romania) – The mechanism of the antiherpetic action of an aqueous propolis extract. II. The action of the lectins of an aqueous propolis extract,
in Rev. Roum. Virol., Jan.-Jun., 44(1-2), pp.49-54 (***).

The report brings proofs of the presence of a lectin in the water propolis extract. It was detected in human fibroblast extracts previously treated with the propolis extract. Presence of the lectin was confirmed by polyacrylamide gel electrophoresis in the presence of SDS.

[xxvii] [26] El-Ghazaly, M. A., & Khayyal, M. T. (1995). The use of aqueous

propolis extract against radiation-induced damage. Drugs Exp Clin Res,

21(6), 229-36, Whole body exposure to gamma radiation has been

experimentally shown to exaggerate inflammatory responses and to enhance

the release of mediators. A thirteen per cent aqueous extract of propolis

(bee glue) was previously shown to have potent antiinflammatory activity.

The present study was carried out to show whether the extract could

influence the exaggerated inflammatory response in irradiated animals. Rats

were exposed to acute (2 and 6 Gy) & fractionated (1 Gy/week) doses of

gamma ionizing radiation. Treatment with the aqueous extract orally (5

ml/kg) before and after radiation exposure markedly reduced the exaggerated

paw oedema response to carrageenan. In the acute phase of adjuvant-induced

arthritis, exposure to ionizing radiation caused an increase in serum acid

phosphatase level. Malondialdehyde concentration in plasma and superoxide

dismutase activity in blood significantly increased. Treatment with aqueous

propolis extract prior to irradiation reduced malondialdehyde concentration

in plasma and normalized the serum acid phosphatase level. The extract

stimulated the release of superoxide dismutase enzyme. Aqueous propolis

extract could possibly be of therapeutic value in protecting against

inflammatory responses induced by gamma radiation.

[xxviii] Esanu, V.; Prahoveanu, E.; Crisan, I.; Cioca, A. (1981) (Romania) – The effects of an aqueous propolis extract, of rutin and of a rutin – quercetin mixture on experimental influenza virus infection in mice (abstract),
in Virologie, Jul. – Sept., 32(3), pp.213-15 (***).

Investigations were performed on the effect of an aqueous propolis extract, of rutin and of a rutin-quercetin mixture on experimental infection with influenza virus A/PR8/34 (H0N1) in mice. Propolis extract administered intranasally 3 hours before virus inoculation led to a reduction of the HA titers recorded in the lung suspensions from infected mice, but to no reduction in mortality or increase in mean survival length. When the extract was administered 3 hours after virus inoculation, the reduction in HA titer was accompanied by a slight decrease in mortality and increase in mean survival length, Rutin and the rutin-quercetin mixture caused an increase in both HA titer and mortality.

[xxix] Esanu, V. (1981) (Romania) – Recent advances in the chemotherapy of herpes virus infections,
in Virologie, 32(1), pp.57-77 (***).
The main categories of antiherpes agents presently used in chemotherapy area reviewed according to the phase of virus replication affected : 1) virus adsorption (adamantane, nonionic surfactants) ; 2) eclipse (interferon) ; 3) virion maturation (nucleoside and nucleotide analogues and phosphonic acid derivatives). Mention is also made of other compounds–different synthetic organic derivatives, photodynamic dyes, metal ions, boric acid, hormones, antibiotics, other natural products (extracts from marine algae, propolis, garlic)–with promising antiviral properties. The difficulties and prospects of viral chemotherapy research are briefly discussed.

[xxx] Laboratorio de Fitoquimica
CEBAS (C.S.I.C.)
P.O. Box 1495
Murcia 30080 (Espagne)
fax: +34-68.266613
email de F.A. Tomas-Barberan: fatomas@natura.cebas.csic.es

[xxxi] Focht,J.; Hansen,S.H.; Nielsen,J.V.; van den Berg-Segers,A.; Riezler,R. (1993) – Bactericidal effects of propolis in vitro against agents causing upper respiratory tract infections (abstract),
in Arzneimittelforschung, Aug, 43(8), p.921-23 (***) .

Propolis is a natural product of bees which exhibits an antimicrobial effect. In the study the existence of a bactericidal effect against several strains isolated from patients with infections in their upper respiratory tracts is demonstrated. In light of the use of propolis as a therapeutic agent in natural medicine for common colds and inflammatory processes this effect is discussed.

[xxxii] Gafar, M.; Dumitriu, H.; Dumitriu, S.; Guti, L. (1989) (Romania) – Apiphytotherapeutic original preparations in the treatment of chronic marginal parodontopathies. A clinical and microbiological study,
in Rev Chir Oncol Radiol O R L Oftalmol Stomatol Ser Stomatol, 36(2), pp.91-8 (***).The paper presents results obtained by the treatment of chronic marginal parodontopathies with natural products of apiarian derivatives and vegetal extracts. These are original preparations such as Proparodont, sage extracts, watercress extracts, etc., by comparison with other similar existing products, and with zinc chloride. The clinical study evaluated the “inflammation status of the marginal parodontium” on the basis of variations in the PMA index. The microbiological study has established the bacteriostatic and the bactericidal activities of the products employed. The results obtained stress the high antimicrobial activity of the original products called Proparodont, and stress its antimycotic effects, especially against Candida albicans. The blackwort (Symphytum off.) extracts have a good repair effect, especially after surgical procedures. The complex original products based on propolis and vegetal extracts are indicated in the treatment of inflammatory lesions of the gingivo-parodontal tissues, and of the buccal mucosa. They also have antimicrobial effects, as well as antimycotic, antiinflammatory and antiscar effects. They de not have side effects which are characteristic for other medicinal drugs employed in the treatment of chronic marginal parodontopathies.

[xxxiii] Giurcaneanu,F.; Crisan, I.; Esanu, V.; Cioca, V.; Cajal, N. (1988) (Romania) – Treatment of cutaneous herpes and herpes zoster with Nivcrisol -D (abstract),
in Virologie, Jan.-Mar. 39(1), pp.21-24.

The results obtained at the Dermatological service of the Colentina Hospital show that the product NIVCRISOL-D, containing propolis, has a significant therapeutical effect against recurrent herpes and zona zoster.

[xxxiv] Cátedra Química General. Facultad de Bioquímica, Química y Farmacia. Universidad Nacional de Tucumán. Ayacucho 491. (4000). San Miguel de Tucumán. República Argentina.
Fax: 54-381-4248025. E-mail: mago@unt.edu.ar

[xxxv] Laboratorio de Referencia de Investigación y Salud Apícola. Circunvalación y Carretera Central. Sancti Spiritus. Cuba

[xxxvi] Cátedra Química General. Facultad de Bioquímica, Química y Farmacia. Universidad Nacional de Tucumán. Ayacucho 491. (4000). San Miguel de Tucumán. República Argentina.
Fax: 54-381-4248025. E-mail: mago@unt.edu.ar

[xxxvii] Cátedra Química General. Facultad de Bioquímica, Química y Farmacia. Universidad Nacional de Tucumán. Ayacucho 491. (4000). San Miguel de Tucumán. República Argentina.
Fax: 54-381-4248025. E-mail: mago@unt.edu.ar

[xxxviii] Laboratorio de Referencia de Investigación y Salud Apícola. Circunvalación y Carretera Central. Sancti Spiritus. Cuba

[xxxix] Abstract

American countries propolis samples deriving from the Apis mellifera bee and known to be biologically active were analysed. Phytochemical screening and quality analyses of 38 propolis samples collected were carried out. The analyses indicated that 2.63% propolis samples contained cardenolide glycosides, 2.63% amines, 71.05% flavonoids, 94.74% triterpenes and/or steroids, 76.31% quinones, and 96.74% lactones; lipids and/or essentials oils, phenols and/or tannins and reducer sugars were found in all samples; alkaloids and saponines were absent. The wax contents varied between 0.06% and 44%, the oxidation index ranged from 1 to 36 seconds, mechanical mixtures from 23.5 to 68.21%, and phenolic compounds from 1.14 to 53.75%.

Key words: propolis, beehive products, phytochemical screening, chemical analyses.

[xl] Grange, J. M.; Davey, R. W. (1990) – Antibacterial properties of propolis (bee glue),
in J R Soc Med, 83(3), pp.159-60 (abstract).
Propolis (bee glue) was found to have antibacterial activity against a range of commonly encountered cocci and Gram-positive rods, including the human tubercle bacillus, but only limited activity against Gram- negative bacilli. These findings confirm previous reports of antimicrobial properties of this material, possibly attributable to its high flavonoid content.

[xli] HASHIMOTO, Takaharu; AGA, Hajime;
TABUCHI, Akihiko; SHIBUYA, Takashi; CHAEN,
Hiroto; FUKUDA, Shigeharu; KURIMOTO, Masashi (1998) (Japan) – Anti-Helicobacter
pylori compounds in Brazilian propolis. Natural Medicins 2(), pp.518-520.

An ethanol extract from Brazilian propolis has antibacterial activity on
Helicobacter pylori, from which two active fractions were obtained by silica
gel column chromatography. From one fraction, an anti-H. pylori compound was
isolated which was identified as 4-hydroxycinnamic acid (p-coumaric acid:1),
and from the other fraction, 3-prenyl-4-hydroxy-cinnamic acid,
3-prenyl-4-dihydrocinnamoloxycinnamic acid, and
3,5-diprenyl-4-hydroxycinnamic acid were isolated, whose anti-H. pylori
activities expressed as the minimal inhibitory concentration (MIC) in mg/ml,
were 15.6-31.3, 62.5, 125, and 250, respectively. 4-Hydroxycinnamic acid
derivatives are likely to be major anti-H. pylori compounds in Brazilian
propolis.

[xlii] Hausen, B.M.; Evers, P.; Stuwe, H. T.; Konig, W. A.; Wollenweber, E. (1992) – Propolis allergy (IV). Studies with further sensitizers from propolis and constituents common to propolis, poplar buds and balsam of Peru,
in Contact Dermatitis 26(1), Jan., pp.34-44.

Abstract
26 different compounds have been investigated experimentally for their sensitizing capacity in guinea pigs. 19 of these occur in propolis as well as in poplar bud exudates, and 14 of them are also found in balsam of Peru. 4 caffeates and benzyl isoferulate were found to be strong sensitizers. 7 compounds were moderate, and 13 compounds showed only weak sensitizing potency. Methyl cinnamate was negative. Patch tests in 11 propolis-sensitive patients once more revealed 3-methyl-2-butenyl caffeate and phenylethyl caffeate as the major sensitizers. In addition to the 8 compounds already known to occur in propolis as well as in balsam of Peru, we detected 5 further substances that both materials have in common. Among these, benzyl isoferulate is considered a noteworthy sensitizer. Coniferyl benzoate, which was shown to be a moderate sensitizer, is present in fresh samples of balsam of Peru, while in propolis it has been detected only once so far. The flavonoid aglycones occurring in poplar bud exudates, and hence also in propolis, are weak sensitizers which play only a minor role in propolis hypersensitivity.

[xliii] Havsteen, H. Bent (1983) (Germany) – Flavonoids, a class of natural products of high pharmacological potency,
in Biochem Pharmacol, 32(7), pp.1141-48 (abstract).

A review has been presented of the biochemistry and pharmacology of a class of natural products, the flavonoids. These substances which are widely distributed in the plant kingdom and present in considerable quantities in common food products, spices and beverages have in a concentrated form (Propolis) been used since ancient times by physicians and laymen to treat a great variety of human diseases but they have yet to pass the tests of modern, controlled, clinical experimentation. An attempt has been made to present the fundamental evidence from the basic biological sciences which is required to stimulate the interest of the clinicians in this new field. The few existing reports on the careful pharmacodynamic, pharmacokinetic and clinical studies which have been made have been summarized to provide a basis for a full-scale investigation of the therapeutic potential of flavonoids.

[xliv] Hegazi, Ahmed Gaffer; El Miniawy, H. F.; El Miniawy F. A. (1995) (Egypt) – Effect of some honeybee products on immune response of chicken infected with virulent NDV (Newcastle Disease Virus),
in Egyptian Journal of Immunology 2 (2), pp.79-86.
ABSTRACT: The effect of some bee products on immune response of chicken infected with virulent Newcastle disease virus was investigated. The mortality rate was reduced in groups infected with virulent Newcastle disease virus and subsequently treated either by propolis or honey if compared with the infected group only. It was cleared that the propolis acts actively better as antiviral agent than honey. The treatment with propolis and honey of NDV infected chicken groups induced increase in the antibody titers and phagocytic percentage.

The inoculation of different antigens in the foot pad of sensitized and non
sensitized chickens induced different degrees of foot pad thickness as well as cellular and vascular reaction depending on the type of the sensitizing antigens in foot pad. The most severe reaction was recorded in the honey & NDV group inoculated with NDV antigen. The reaction was typical to Arthus type. In propolis group inoculated with NDV antigen, the reaction was differed and the lymphocytes appeared to play the main role in this reaction which became a delayed type of hypersensitivity.

[xlv] National Research Center and *Animal Health Research Institute, Dokki, Giza, Egypt.

Fax: +2023370931 – Email: ahmedgaffer@frcu.eun.eg // samira@mena.org.eg

[xlvi] Abstract

Four propolis samples from Austria, Egypt, France and Germany were investigated by GC/MS, where twenty compounds were being new for propolis. The samples showed some similarities in their qualitative composition. Phenylethyl-trans-caffeate, benzyl ferulate and galangin were predominant in German propolis. Benzyl caffeate was predominant in French sample. Pinocembrin was predominant in French and Austrian propolis and trans-p-coumaric acid was predominant in all samples. Egyptian propolis is characterized by the presence of unusual esters of caffeic acid with C12- C16 fatty alcohols, mainly saturated.

The antiviral activity propolis samples from Austria, Egypt, France and Germany against avian Roe virus and Infectious Bursal Disease virus was evaluated. All propolis samples reduced the viral infectivity but it is varied according to the propolis origin. Egyptian propolis showed the highest antiviral activity against Roe virus and Infectious Bursal Disease virus.

Key words: Propolis, GC/MS, Polyphenols, Antimicrobial Activity.

[xlvii] Propolis (bee glue) is the substance used by bees as a draught exuded and general purpose scalar for their hives. Propolis contains a number of phenolic constituents with antimicrobial, antifungal, antiviral, immunostimulant and antioxidant activities.

Egyptian propolis was analyzed by gas chromatography mass spectrometry. 31 peaks were located of which 26 representing 25 compounds were identified. Seven compounds were identified in Egyptian propolis for the first time.

The constituents were phenolic acid esters (72.7 %); phenolic acids (1.1 %); aliphatic acids (2.4 %); dihydrochalcones (6.5 %); Chalcones (1.7 %); flavanones (1.9 %); flavones (4.6 %) and tetrahydrofuran derivatives (0.7 %). It was clear that phenolic acid esters are present in a major quantity (72.7 %).

Evaluation of Egyptian propolis as immunostimulant, antiviral, antibacterial and antifungal agent were done and showed that the Egyptian propolis has such activities.

[xlviii] Propolis from different countries with different climate were investigated, the main plant source of propolis being always poplar buds. Investigations were concentrated on “balsam” (extract with 70% ethanol). Propolis samples from Albania, Austria, Bulgaria, France, Egypt, Germany and Mongolia have been investigated and the results obtained compared with propolis from England.

Egyptian, Albanian, Austrian, Bulgarian, French, German, Mongolian and British propolis showed significant qualitative similarities. The quantitative differences obtained could be due to the participation of different poplar species. In some regions small amount of propolis could be collected from other plants, too. Egyptian propolis is characterized by the presence of unusual esters of caffeic acid with C12- C16 fatty alcohols, mainly saturated. These esters have not been found till now in propolis. A series of triterpenes in Egyptian propolis, lanosterol were also identified. Phenylethyl-trans-caffeate, pinokansin acetate and galangin were predominant in German propolis. Pinocembrin was predominant in Bulgarian and British propolis and trans-p-coumaric acid was in German and British.3-methyl-2-butenyl-caffeate was predominant in Mongolian and Albanian propolis and 3-methyl-3-butenyl-caffeate in Albanian propolis only.

The antimicrobial activity of propolis collected from different countries against Staphylococcus aureus; Escherichia coli, and Candida albicans were investigated. All propolis samples showed an inhibition in the growth of all examined microorganisms but the inhibition varied according to the propolis origin. It was obvious that German and Egyptian propolis showed the highest antimicrobial activity against Staphylococcus aureus while it was highest in Mongolian, German and Egyptian propolis against Escherichia coli, but Egyptian and Austrian propolis has the highest activity against Candida albicans.

[xlix] Higashi, K. O.; de Castro, S. L. (1994) – Propolis extracts are effective against Trypanosoma cruzi and have an impact on its interaction with host cells,
in J Ethnopharmacol,July, 8; 43(2), pp.149-155 (abstract).

Propolis, a natural resin produced by honey bees, that displays strong antimicrobial activity, has been used as a chemotherapeutic agent since ancient times. The anti-protozoan properties of different propolis extracts were studied regarding T. cruzi and its interaction with host cells. Ethanolic (EEP) and dimethylsulphoxide extracts (DEP) were both active against the three forms of the parasite, with the former being more active than the latter against the vertebrate forms, amastigotes and trypomastigotes. Total lysis of bloodstream trypomastigotes was observed after 24 h in the presence of EEP at a concentration of 100 micrograms/ml. The effect was found to be temperature dependent. Treatment of infected peritoneal macrophages and heart muscle cells with EEP strongly inhibited infection levels. The utilization of propolis as a possible antitrypanosomal agent is discussed.

[l] Ikeno, K.; Ikeno, T.; Miyazawa, C. (1991) – Effects of propolis on dental caries in rats,
in Caries Res, 25(5), pp.347-51 (abstract).

Propolis, the resinous hive product collected by bees, is important in the defense of the hive. The effects of propolis on growth and glucosyltransferase activity of Streptococcus sobrinus 6715, Streptococcus mutans PS14 and Streptococcus cricetus OMZ61 in vitro, and on dental caries in rats infected with S. sobrinus 6715 were investigated. Propolis had antimicrobial activity against S. sobrinus, S. mutans and S. cricetus, and inhibited both water-insoluble glucan synthesis and glucosyltransferase activity. In rats inoculated with S. sobrinus, about half of their fissures were carious, while dental caries was significantly less (p = 0.01) in rats given propolis. Dental caries was markedly decreased by the multiple actions of propolis which had antimicrobial activity, inhibited water-insoluble glucan synthesis, and inhibited glucosyltransferase activity. No toxic effects of propolis on the growth of rats were observed under experimental conditions in this study. These results suggest that propolis can control dental caries in the rat model system.

[li] Ivanovska N. D.; Dimov V. B.; Pavlova S.; Bankova Vassya.; Popov S. S. (1995) (Bulgaria) – Immunomodulatory action of propolis. V. Anticomplementary activity of a water-soluble derivative,
in Journal of Ethnopharmacology 47(3), Jul 28, pp.135-43.

Abstract
The effect of a water-soluble derivative (WSD) of propolis on the classical pathway (CP) and the alternative (AP) complement activity has been investigated. The in vitro experiments show that WSD inhibits both pathways and the effect depends on the source of complement. The suppression of complement-mediated haemolysis proves to be time- and temperature-related. High WSD concentrations cause direct damage of the target erythrocytes. The estimation of C3-residual activity indicates that the preparation diminishes C3 functional activity.

[lii] Ivanovska, N. D.; Dimov, V. B.; Bankova, V. S.; Popov, S. S. – Immunomodulatory action of propolis. VI. Influence of a water soluble derivative on complement activity in vivo,
in J Ethnopharmacol, 47(3), pp.145-7 (abstract).

The water soluble derivative (WSD) of propolis in a dose of 150 mg/kg was administered intravenously (i.v.), intraperitoneally (i.p.) and orally (p.o.) to mice. The alteration of serum alternative pathway (AP) complement level was observed. The WSD also influenced the process of acute inflammation provoked by zymosan in mice. The effect was strongly dependent on the route of WSD administration.

[liii] Jaiswal, A. K.; Venugopal, R.; Mucha, J.; Carothers, A. M.; Grunberger, D. (1997) – Caffeic acid phenethyl ester stimulates human antioxidant response element-mediated expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene,
in Cancer Res, 57(3), pp.440-46 (abstract).

Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant derived from the propolis of honeybee hives. CAPE was shown to inhibit the formation of intracellular hydrogen peroxide and oxidized bases in DNA of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated HeLa cells and was also found to induce a redox change that correlated with differential growth effects in transformed cells but not the nontumorigenic parental ones. Mediated via the electrophile or human antioxidant response element (hARE), induction of the expression of NAD(P)H quinone oxidoreductase (NQO1) and glutathione S-transferase Ya subunit genes by certain phenolic antioxidants has been correlated with the chemopreventive properties of these agents. Here, we determined by Northern analysis that CAPE treatment of hepatoma cells stimulates NQO1 gene expression in cultured human hepatoma cells (HepG2), and we characterized the effects of CAPE treatment on the expression of a reporter gene either containing or lacking the hARE or carrying a mutant version of this element in rodent hepatoma (Hepa-1) transfectants. A dose-dependent transactivation of human hARE-mediated chloramphenicol acetyltransferase (cat) gene expression was observed upon treatments of the Hepa-1 transfectants with TPA, a known inducer, as well as with CAPE. The combined treatments resulted in an apparent additive stimulation of the reporter expression. To learn whether this activation of cat gene expression was effected by protein kinase C in CAPE-treated cells, a comparison was made of cat gene activity after addition of calphostin, a protein kinase C inhibitor. Calphostin reduced the cat gene induction by TPA but not by CAPE, suggesting that stimulation of gene expression in this system by these agents proceeds via distinct mechanisms. Band-shift experiments to examine binding of transactivator proteins from nuclear extracts of treated and untreated cells to a hARE DNA probe showed that TPA exposure increased the binding level. In contrast, binding of factors to this probe was inhibited after either in vivo treatment of cells with CAPE or in vitro addition of this compound to the nuclear extract. In view of the clear stimulation by CAPE of gene expression mediated by hARE, possible explanations of this result are discussed.

[liv] Kaminski, M.; Scheller, Stanislaw; Nolewajka, E. (1977) – Biological properties and clinical application of propolis. V. The action of ethanol extract of propolis (EEP) on laboratory animals. Histochemical investigations,
in Arzneimittelforschung, 27(10), pp.1962-64 (abstract).

In the experiment on rats the ethanol extract of propolis (EEP) injections caused an activation of all experimental enzymes. The greatest effect EEP exerted was on NADPH2 tetrazolium reductase and glucose-6-phosphatase.

[lv] Khayyal, M. T.; el-Ghazaly M. A.; el-Khatib, A. S. (1993) – Mechanisms involved in the antiinflammatory effect of propolis extract,
in Drugs Under Experimental & Clinical Research 19(5), pp.197-203.
Abstract
Propolis is a natural product produced by the honey bee. The extract contains amino acids, flavanoids, terpenes and cinnamic acid derivatives. In various in vitro models propolis extract was shown to inhibit platelet aggregation and to inhibit eicosanoid synthesis, suggesting that it might have potent antiinflammatory properties. A 13% aqueous extract was tested orally in three dose levels (1, 5 and 10 ml/kg) on the carrageenan rat paw oedema model and on adjuvant-induced arthritis in rats. In both models, the extract showed potent dose-related antiinflammatory activity, which compared well with that of diclofenac (as a reference standard). The extract was then tested on an isolated sensitized guinea pig lung preparation to study its effect on the release of prostaglandins, leukotrienes and histamine. It is concluded that propolis extract has potent antiinflammatory properties in vivo. Its activity can be well correlated with its effects on the release of various mediators of inflammation.

[lvi] IMKEREIERZEUGNISSE IN DER KOMPLEXEN BEHANDLUNG

DER PATIENTEN MIT CHRONISCHER BRONCHITIS

N.D. Kirienko
A.I. Tcherkasova
L.I. Zaharteva
V.P. Gladtchun
V.A. Klevanik
L.A. Kiiko (USSR)

Bei 104 Patienten mit chronischer Bronchitis erfolgte die Analyse der Dynamik der Laborkennwerte, der klinischen Daten, der nichtspezifischen Widerstandsfähigkeitskennwerte und der Immunoglobuline. Bei 56 Patienten wurden traditionelle Behandlungsmethoden angewandt, bei 48 Patienten wurden auch Propolis und Honig inhaliert. Der Vergleich der klinischen, Labor- und Immunoglobulin-Indizes bewies die Wirksamkeit der Einführung von Honig und Propolis in die komplexe Behandlung der Patienten mit chronischer Bronchitis. Die Aufenthaltdauer in der Heilanstalt wurde um 3-4 Tage verkürzt. Außerdem war gegenüber der Kontrollgruppe die Rückfäligkeit der Krankheit in der Versuchsgruppe zweimal niedriger.
S.524

[lvii] Kosenko, S. V.; Kosovich, T. (1990) – The treatment of periodontitis with prolonged-action propolis preparations (clinical and x-ray research),
in Stomatologiia (Mosk),Mar.-Apr. 69(2), pp.27-9 (abstract).

A 4% alcohol solution of bee glue is suggested to be added to the filler for root-canal filling, besides the traditional treatment of the root canals with bee glue solution. Clinical and x-ray examinations have demonstrated a high efficacy of such technique in acute, exacerbated, and chronic forms of periodontitis. This filler is characterized by an anesthetizing effect; it resolves behind the root canal apex within 3-12 months, is preserved in the root canals, does not stain the tooth crown, promotes regeneration of the bone structures, and prolongs the effect of 0.4% water-alcohol bee glue emulsion.

[lviii] Kujumgiev, Tsvetkova and Sekedjieva are working at the Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria. Bankova, Christov and Popov are working at the Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.

[lix] Lambert, Priscila (1999) (Brazil) – Pesquisa mostra que resina produzida pelas abelhas impede o crescimento de células cancerígenas. Própolis pode proteger corpo de tumores,
in Folha de São Paulo, 12 de Julho de 1999.

Investigación muestra que la resina producida por las abejas impide el crecimiento de células cancerígenas.

El Própoleo puede proteger al cuerpo de tumores.

PRISCILA LAMBERT

de un Reportage Local

El propoleo, aquella resina que las abejas producen para proteger la colmena de invasores, también puede tener propiedades que protegen al cuerpo humano de “invasores”.

Un estudio realizado en Brasil recientemente demostró que determinados tipos de propoleos impedirían el crecimiento de células cancerígenas en estúdios de laboratorio. La investigación fué realizada por el bioquímico Yong Kun Park, profesor titular de la Facultad de Ingenieria de Alimentos de Unicamp (Universidade Estadual de Campinas).

El ya había sido director en una tesis que concluyó que ciertos tipos de propoleos inhiben la acción de la bacteria Streptococcus mutans, causadora de carie dentaria (lea el texto en esta página).

El profesor viene estudiando la actividad del propoleo desde 1990. Fueron analizadas 400 muestras recolectadas en todas las regiones del país.

Muestras

La primer conclución, despues de un test de cromatografia (una especie de fotografía de los compuestos químicos), fue la de que, dentro de las 400 muestras, 12 eran diferentes entre sí. O sea, existen por lo menos 12 tipos de propoleos en Brasil, que varían de coloración y composición.

Solamente en la región sur, Park descubrió siete tipos diferentes de resina. “El país tiene una biodiversidad muy rica, lo que explica las variaciones de propoleos. En paises europeos o en EUA, las resinas de las abejas son todas iguales”, dice el profesor. “Cada tipo de propoleo brasilero tiene una propiedad antimicrobiana o antibiótica diferente”.

En su estúdio, los 12 tipos de propoleos fueron colocados en contacto con diferentes células cancerosas –del intestino, riñon, mamas, nariz y faringe.

Tiempo

Despues de dos semanas –tiempo sufuciente para que las células se repordujeran y crecieran-, diez muestras habían presentado, en diferentes grados, no solo la inhibición de crecimiento, sino la destrucción parcial de las células.

La muestra que presentó el mejor resultado fué un tipo de propoleo de Bahia (BA-8), que redujo las celulas de cancer nasofaríngeo en 97% y de mama en 96%, entre otros (vea quadro al lado).

El método de cálculo de inhibición de tumores utilizado en el estudio tuvo como base de comparación los resultados obtenidos por la droga Etoposide, la más fuerte existente en el mercado para combatír el cancer. Ese método fué desarrollado por el Instituto Nacional del Cancer de los EUA.

Los resultados presentados en el estúdio de Park fueron confirmados en un test realizado por investigadores norteamericanos de la Universidad de Carolina del Norte (EUA).

La investigación rindió al profesor Park una invitación para pasar el próximo mes como profesor-visitante de la universidad norteamericana, donde comenzará nuevos estudios, ahora para descubrir cuales son los compuestos químicos presentes en el propoleo y responsables por la acción anticancerígena.

[lx] Lambert, Priscila (1999) (Brazil) – Própolis puede proteger del sol,
in Folha de São Paulo, 12 de Julho de 1999.

Outra propiedad atribuída al propoleo es la de filtrar los rayos ultravioletas tipo B.

La farmacéutica Ana Luíza Mori, responsable por la farmacia universitaria de la Facultad de Ciencias Farmacéuticas de la USP, desarrollo una monografía de maestrado sobre esa acción del propoleo.

Ella utilizó extractos de propoleos de diferentes regiones del país y del mundo para crear bases cosméticas, que fueron sometidas a un aparato que mide el grado de absorción de rayos ultravioletas.

Como resultado, Ana Luíza obtuvo factores de protección de los rayos UVB que variaron de 1 (protección casi nula) hasta 8, en la muestra de propoleo de Pensilvania (EUA).

“La utilización del propoleo como medicamento fitoterápico es complicada, porque la composición de la resina varía de acuerdo com el suelo, la vegetación y la época del año”, dice.

[lxi] Lambert, Priscila (1999) (Brazil) – Carie en ratones fué reducida,
in Folha de São Paulo, 12 de Julho de 1999.

Estudios realizados com ratones de laboratório sugieren que el propoleo también inhibe la acción de bactérias causadoras de carie dentaria.

El bioquímico Yong Kun Park, de la Unicamp, realizó una investigación semejante la que demotró que algunos tipo de propoleo inhiben el crecimiento de la células cancerígenas.

Colocó 200 muestras recogidas en el país en contacto com cultivos de la bactéria Streptococcus mutans, principal causadora de las caries. Una de ellas, encontrada en Rio Grande Do Sul y en Paraná, inhibió el crecimiento del cultivo.

A partir de ese estúdio, el cirujano-dentista Michel Hyunkoo, elumno de Park, resolvió, en su monografiía de maestrado, aplicar el test a los animales.

El usó 30 ratas infectadas com la bacteria, divididos en tres grupos: uno de ellos recibió propoleo de Minas Gerais, outro, de Rio Grande do Sul. El tercer grupo no recibió propoleo. Por tres semanas, los animales fueron alimentados com una dosis exagerada de sacarosa y recibieron aplicaiones de propoleo sobre los dientes dos veces al día. El mejor resultado fué obtenido com el propoleo de Rio Grande do Sul. Los animales mantuvieron el esmalte dentario conservado, com inhibición del 60% de la acción de las bacterias. El grupo sometido al propoleo de Minas Gerais presentó algunas caries, com un índice de inhibición menor, entre 20% y 30%.

La ratas que no recibieron propoleo presentaron la superficie dentaria totalmnte destruída.

“Su acción depende del tipo de propoleo usado. De 200 muestras, solo una se mostro eficaz”, dice Hyunkoo.

Com esse estudio, Hyunkoo ganó el premio Joven Investigador en el área de prevención de enfermedades bucales de América Latina, ofrecido por la Asociación Internacional para Investigación en Odontología, com sede en los EUA.

[lxii] Lin, S. C.; Lin, Y. H.; Chen, C. F.; Chung, C. Y.; Hsu, S. H. – The hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries,
in Am J Chin Med, 25(3-4), pp.325-32 (abstract).

Propolis designates a mixture of gums, resins and balms, of viscous consistency, which are gathered on certain parts (buds and bark, mainly) of vegetables (especially coniferous trees) by honeybees. They bring this back to the hive, where it is modified and mixed with other substances (essentially their own wax and salivary secretions). In this study, the hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries were investigated in rats. 3.125 ml of 99.5% alcohol was added to animal’s daily diet for four weeks to induce chronic alcohol liver injuries. After sacrifice, serum transaminases (GOT, GPT), triacylglyceride and hepatic triacylglyceride (HTG) concentration were assayed to observe liver injuries induced by chronic alcohol abuse. In addition, the phenomenon of alcohol induced fatty liver were also observed by histopathological changes. Different doses of propolis ethanol extract were p.o. administered three times per day for three days, after four weeks’ alcohol administration. It was found that 10 mg/kg of propolis ethanol extract significantly decreased the elevations of serum GOT, GPT, TG and HTG. In histopathological examination, 30 mg/kg of propolis ethanol extract also remarkably decreased the hepatocellular fatty degeneration, apparent as vacuolization, induced by chronic alcohol abuse.

[lxiii] Ludianskii, E. A. (1990) – Dissociated symptoms of the progressive course of brain injury,
in Zh Nevropatol Psikhiatr Im S S Korsakova, 90(7), pp.53-5 (abstract).

Hypotension of the cerebrospinal fluid (CSF) was detected in 18% of 856 patients with brain trauma examined in the study. Three syndromes of dissociated hypotension of the CSF were described: (1) at the level of the Magendie-Luschka openings; (2) at the level of the aqueduct of Sylvius; (3) at the level of the third ventricle. Each level of hypotension of the CSF was attended by a specific clinical syndrome. The parameters of the progressive course of the disease made it possible upon their identification to begin the rehabilitation of patients at the earliest stage which led to a faster compensation. Special attention was given to apitherapy, phytococtails and instillations of special coctails for controlling the dissociation between CSF hypotension and hydrocephaly. The conducted rehabilitation made it possible to significantly reduce the incidence of crises indicative of the decompensation of brain injury.

[lxiv] Machackova, J. (1988) (Czechoslovakia) – The incidence of allergy to propolis in 605 consecutive patients patch tested in Prague,
in Contact Dermatitis, Apr.; 18(4), pp.210-12 (abstract).

605 consecutive patients were patch tested with the standard CDRG test series and with a 10% alcoholic solution of propolis. Positive allergic reactions to propolis were observed in 25 patients (4.2%); thirteen of them exhibited a simultaneous positive patch test to balsam of Peru. In view of the relatively high incidence of allergic reactions and the appearance of pseudo-cross-sensitivity to another common allergen, balsam of Peru, propolis should not be used in topical medicaments or as a component of cosmetic preparations.

[lxv] Magro Filho, O.; de Carvalho, A. C. (1990) – Application of propolis to dental sockets and skin wounds,
in J-Nihon-Univ.-Sch.-Dent., Mar.; 32(1), pp.4-13 (abstract).

The purpose of this study was to examine histologically the effects of propolis topical application to dental sockets and skin wounds. After topical application of either a 10% hydro-alcoholic solution of propolis or 10% hydro-alcoholic solution alone, cutaneous wound healing and the socket wound after tooth extraction were examined. The rats were sacrificed at 3, 6, 9, 15 and 21 days after the operation. The specimens were subjected to routine laboratory studies after staining with hematoxylin and eosin. It was concluded that topical application of propolis hydro-alcoholic solution accelerated epithelial repair after tooth extraction but had no effect on socket wound healing.

[lxvi] Magro-Filho, O.; de Carvalho, A. C. (1994) – Topical effect of propolis in the repair of sulcoplasties by the modified Kazanjian technique. Cytological and clinical evaluation,
in Journal of Nihon University School of Dentistry 36(2), Jun, pp.102-11.

Abstract
A study was conducted to analyze the effects of propolis mouth rinse on the repair of surgical wounds after sulcoplasty by the modified Kazanjian technique. Twenty-seven patients who underwent sulcoplasty were divided into three groups: C1–patients who did not use the mouth rinse C2–patients who used a mouth rinse containing 5% aqueous alcohol T–patients who used a mouth rinse containing 5% propolis in aqueous alcohol solution. The patients returned 7, 14, 30, and 45 days after surgery for cytological and clinical evaluation. It was concluded that: 1) the mouth rinse containing propolis in aqueous alcohol solution aids repair of intra-buccal surgical wounds and exerts a small pain-killing and anti-inflammatory effect; 2) the vehicle employed has a minor irritant effect on intra-buccal surgical wounds; 3) exfoliative cytology allows epithelization of intrabuccal surgical wounds.

[lxvii] Mahran, L. G.; el-Khatib, A. S.; Agha, A. M.; Khayyal, M. T. (1996) (Egypt) – The protective effect of aqueous propolis extract on isolated rat hepatocytes against carbon tetrachloride toxicity,
in Drugs Exp Clin Res., 22(6), pp.309-16.

Authors address: Department of Pharmacology, Faculty of Pharmacy, Cairo University, Egypt.

The protective effect of honeybee aqueous propolis extract (APE) against the hepatotoxicity of carbon tetrachloride was investigated using isolated liver-cell suspensions as the experimental model. Various concentrations of the extract were preincubated with the hepatocyte suspensions for 30 min before being subjected to the hepatotoxin for a further 30 min. The hepatocyte toxicity was assessed using three parameters, namely, the release of lactate dehydrogenase, the formation of lipid peroxides and the depletion of intracellular reduced glutathione. It was found that a dose-related protection against the induced cell injury was conferred by APE as evidenced by its inhibitory influence on the changes induced by CCl4 on the measured parameters. The hepatocyte protective effect of APE is probably a result of its antioxidant and free-radical-scavenging properties which in turn help to maintain the intracellular level of reduced glutathione.
PMID: 9034757, UI: 97187304.

[lxviii] Maichuk Iu, F.; Orlovskaia, L. E.; Andreev, V. P. (1995) – The use of ocular drug films of propolis in the sequelae of ophthalmic herpes,
in Voen Med Zh(12), 36-9, p.80 (abstract).

There was studied the therapeutic efficiency of ocular medical propolis films (OMF) in 35 patients with postherpetic trophic keratitis and in 20 with postherpetic nebula. OMF were applied behind the lower eyelid at bedtime during 10-15 days. All the patients endured the propolis films well. OMF accelerated the cornea epithelization. Epitheliopathy and micropoint edema of cornea epithelium rapidly disappeared. Time of patients recovery reduced nearly twice (P,001) in comparison with the control group–from 14.1 to 7.6 days. On the average their visual acuity increased in two times–from 0.12 to 0.27 (P > 0.001).

[lxix] Martinez Silveira, G.; Gou Godoy, A.; Ona Torriente, R.; Palmer Ortiz, M. C.; Falcon Cuellar, M. A. (1988, 1991) – Preliminary study of the effects of propolis in the treatment of chronic gingivitis and oral ulceration (Spanish),
in Rev-Cubana-Estomatol., Sept-Dec., 25 (3), 1988, p.36-44 (abstract) ;
in Kaal, 1991, pp.37-38 (***).
Since many years ago are known curative effects of propolis on different lesions due, mainly, to more than 30 biologically active elements isolated from it. It is a wordly accepted opinion that propolis is one of the most useful substances elaborated by bees. Despite it, its use in our country is relatively recent. Several investigators, specially in Matanzas, study curative effects of propolis in the field of human and animal medicine. In other countries it has been used in stomalogy, but we have no knowledge about its therapeutical effects in the periodontal disease or its effectiveness in oral ulcers. Therefore, a therapeutical form has been elaborated, which is provisionally called Propolan, for the treatment of two entities: chronic gingivitis and stomatitis of different etiology. The clinical cases supporting effectiveness found with the treatment applied in our setting are presented.

[lxx] Masterov, G. D. (1995) – Apitherapy in the combined treatment of patients with pulmonary tuberculosis taking into account the hypophyseal-adrenal system indices,
in Lik Sprava(1-2), pp.120-2 (abstract).

Apitherapy (venom of bees and apiculture products) was included into combined treatment of 93 in-patients with pulmonary tuberculosis. Apitherapy had a beneficial effect on the organism of tuberculosis patients, manifested by enhancement of the treatment effectiveness and normalization of indices of endocrine system. It is recommended that the instruction on apitoxinotherapy be amended, in particular, by substantially supplementing the paragraph with indications and contraindications for giving it in active tuberculosis.

[lxxi] Masterov, G. D.; Nersesian, O. N. (1995) – The role of apitherapy in the combined treatment of patients with chronic nonspecific lung diseases,
in Lik Sprava(3-4), pp.155-58 (abstract) .

The authors suggest that apitherapy should be used in the treatment of patients with chronic non-specific pulmonary diseases (ChNPD) in order that it might be more effective. Apitherapeutic complex (bee venom and bee keeping apiculture produce) has been applied to the treatment of 104 ChNPD patients. High effectiveness of apitherapy in a combined treatment of ChNPD patients was demonstrated as was their stimulating and normalizing influence on the function of the adrenals.

[lxxii] Propolis Researchers Association (J Association c/o Faculty of Agriculture, Tamagawa Univ., Machida-shi, Tokyo 194-8610.

“Propolis Researchers Association was established in November, 1997.

In the first seminar, two Brazilian professors and two Japanese gave talks on production, nature and application of propolis in past and in future.

Disconnection among researchers, producers, and consumers was pointed and future activities of the association was promised to offset the gap.

Consumption of propolis in Japan has increased rapidly during a decade, paralleling with the advances of research on propolis.

Japan Propolis Association, composed of ca. 200 member companies, celebrated 10 years anniversary of the establishment in 1997, has their standard for the alcohol extracts, but is struggling with water soluble propolis products.

Collaboration will be needed throughout the world, especially among the researchers themselves and organizations such as Apimondia and other domestic associations in the concerned countries.”

[lxxiii] National Institute of Health, Tokyo, Japan.

[lxxiv] A tumoricidal substance was isolated from Brazilian propolis as guided by cytotoxicity assay on HuH 13 (human hepatocellular carcinoma) cell and was characterized to be 3-[4-hydroxy-3,5-bis (3-methyl-2-butenyl)

phenyl]-2-propenoic acid (3,5-diprenyl-4-hydroxycinnamic acid (artepillin

C)). It exhibited preferential cytotoxicity to tumor cells cultured in

vitro. The cytotoxicity observed seemed to be partly attributable to

apoptosis-like DNA fragmentation. The compound showed anti-tumor activity more effective than that of 5-fluorouracil to transplantable human tumor cell lines when tested on histoculture drug response assay system.

[lxxv] Merino, N.; Gonzalez, R.; Gonzalez, A.; Ramirez, D. (1996) – Histopathological evaluation on the effect of red propolis on liver damage induced by CCl4 in rats,
in Arch Med Res, 27(3), pp.285-89 (abstract).

A histopathological evaluation was performed on liver of rats treated with carbon tetrachloride (CCl4) and 25,50 and 100 mg/kg of Cuban red propolis (RP) extract. Additionally, alanine aminotransferase (ALT) in serum and liver triglycerides were determined in all animals. The morphometric study included the count of ballooned cells at the zone III of the Rappaport acini and the assessment of a software program to estimate the extension of steatosis area. A significant reduction of ballooned cells count in liver was observed at three dose levels of RP extract with respect to rats treated only with CCl4. Also, a certain reduction of steatosis degree as well as decreased concentration of liver triglycerides and ALT activity were found in three groups of rats treated with RP extract and CCl4 in relation to those treated with the hepatotoxin. Taken together, the histopathological and biochemical findings show hepatoprotective effects of RP extract in CCl4-induced liver damage in rats, probably due to the antioxidant effect of RP.

[lxxvi] Metzner, J., Schneidewind, E.M. (1978) (Germany) – Einfluß von Pinocembrin auf den Verlauf der experimentellen Candida – Infektion der Maus (Effect of pinocembrin on the course of experimental candida infections in mice),
in Mykosen, 21 (8), pp.257-62 (abstract).

Pinocembrin (5,7-dihydroxy-flavanone)–a component of the bee product propolis–was tested for its in vivo activity against Candida albicans in mice. It was shown that the intravenous infection of AB-Jena mice with 2.5 X 10(5) Candida albicans cells was a very suitable model. Despite of treatment with pinocembrin at daily doses of 100 mg/kg body weight the animals as well as the controls died between the 6th and 24^th day after beginning. On the other hand the animals treated with 5 mg/kg amphotericin B survived the test-period of 30 days. The question of effectiveness of pinocembrin in vivo should be cleared up in further pharmacokinetic investigations.

[lxxvii] Metzner, J.; Bekemeier, H.; Paintz, M.; Schneidewind, E. (1979) – Zur antimikrobiellen Wirksamkeit von Propolis und Propolisinhaltstoffen (On antimicrobial activity of propolis and its constituents),
in Pharmazie, 34 (2), pp.97-102 (abstract).
After a survey of the literature on the antimicrobial activity of the bee product propolis, the authors discuss their own findings as compared to the chemotherapeutical agents streptomycin, oxytetracycline, chloramphenicol, nystatin, griseofulvin and sulphamerazine. According to the results obtained by testing 25 isolated constituents on Bacillus subtilis, Staphylococcus aureus, Candida albicans and Trichophyton mentagrophytes, the antimicrobial properties of this mixture of natural substances are mainly attributable to the flavonoids pinocembrin, galangin, pinobanksin, pinobanksin-3-acetate as well as to the p-coumaric acid benzyl ester and a caffeic acid ester mixture. None of the isolated substances was as potent as the antibiotics tested for the purpose of comparison. The relatively good antimycotic activity of the 5,7-dihydroxyflavanone (pinocembrin) seems noteworthy.
Finally, possible mechanisms of the antimicrobial action of the flavonoids are discussed.

[lxxviii] Mirzoeva, O. K.; Calder, P. C. (1996) – The effect of propolis and its components on eicosanoid production during the inflammatory response,
in Prostaglandins Leukot Essent Fatty Acids, 55(6), pp.441-49 (abstract).

To investigate the possible mechanism of the therapeutic action of propolis, we studied: (a) the effect of propolis, its components, caffeic acid phenethyl ester (CAPE), caffeic acid (CA), quercetin and naringenin, as well as the synthetic compounds indomethacin (IM) and nordihydroguaiaretic acid (NDGA), and a novel lipoxygenase inhibitor N,N’-dicyclohexyl-O-(3,4-dihydroxycinnamoyl)isourea (DCHCU) on eicosanoid production by mouse peritoneal macrophages in vitro; (b) the effect of IM, NDGA, CA, CAPE, DCHCU and propolis on eicosanoid production during acute inflammation in vivo; and (c) the ex vivo and in vivo effect of dietary propolis on arachidonic acid metabolism. The ethanol extract of propolis suppressed prostaglandin and leukotriene generation by murine peritoneal macrophages in vitro and during zymosan- induced acute peritoneal inflammation in vivo. Dietary propolis significantly suppressed the lipoxygenase pathway of arachidonic acid metabolism during inflammation in vivo. CAPE was the most potent modulator of the arachidonic acid cascade among the propolis components examined.

[lxxix] Mirzoeva, O. K.; Grishanin, R. N.; Calder, P. C. (1997) – Antimicrobial action of propolis and some of its components: the effects on growth, membrane potential and motility of bacteria,
in Microbiol Res, 152(3), pp.239-46 (abstract).

The effect of the natural bee product propolis on the physiology of microorganisms was investigated using B. subtilis, E. coli and R. sphaeroides. An ethanolic extract of propolis had a bactericidal effect caused by the presence of very active, but labile, ingredients. The exact bactericidal effect of propolis was species dependent: it was effective against gram-positive and some gram-negative bacteria. Propolis and some of its cinnamic and flavonoid components were found to uncouple the energy transducing cytoplasmic membrane and to inhibit bacterial motility. These effects on the bioenergetic status of the membrane may contribute to the antimicrobial action of propolis and its observed synergism with selected antibiotics.

[lxxx] Miyares, C.; Hollands, I.; Castaneda, C.; Gonzalez, T.; Fragoso, T.; Curras, R.; Soria, C. (1988) – Clinical trial with a preparation based on propolis “propolisina” in human giardiasis,
in Acta Gastroenterol Latinoam, 18(3), pp.195-201 (abstract);
in Kaal, 1991, p.38 (***).
The results of a clinic assay with an extract made out of propolis (bee glue) or “Propolisina” were showed with the aim of showing its effectivity against giardiasis. One hundred and thirty eight patients were studied 48 children and 90 adults, in 2 groups and they selected aleatorily to be treated with “Propolosina” or an imidazole derivate (tinidazole). The method for an exact diagnosis in children was duodenal aspiration and in adults duodenal mucosa frotis by means of duodenoscopy. Similar studies were carried out as a cure criterium in a 5-day term after being through with the treatment. Propolisina was used with different concentrations: in children (concentration at 10%) results showed a 52% cure. In 40 adults (concentration at 20%) it was obtained a similar result to that of tinidazole; and when propolisina concentration was elevated at 30% in the remaining 50 patients there was a higher effectivity (60 of cure Vs 40% with tinidazole). This work shows the success of this natural product, which is very easy to obtain in Cuba and with no side effects in the treatment of this intestinal parasitism, what is of great economical importance for our countries.

[lxxxi] ABSTRACT:

Native and purified HBsAg preparations were subjected in

vitro to the action of cetylpyridinium bromide (Bromocet),

hibitan-chlorhexidine (Hibiscrub), chloramine B and

propolis extract, at different concentrations and for various

time intervals. The effect of these agents on the serological

reactivity of HBsAg was tested by electroimmunodiffusion

(EID) and radioimmunoassay (RIA). Chloramine B and the

propolis extract had a significant inhibitory

effect-ascertained by both EID and RIA – on purified

HBsAg, but not on the native preparation. The inhibition

exerted by Bromocet and Hibiscrub indicated by EID

results was not confirmed by RIA.

CITATION IDS: PMID: 7257176 UI: 81251020.

[lxxxii] Murray, M. C.; Worthington, H. V.; Blinkhorn, A. S. (1997) – A study to investigate the effect of a propolis-containing mouthrinse on the inhibition of de novo plaque formation,
in J Clin Periodontol, 24(11), pp.796-98 (abstract).

The results of a study to investigate the effectiveness of a propolis-containing mouthrinse in the inhibition of de novo plaque formation are presented. Subjects used a propolis-containing rinse, a negative control and a positive control in a double-blind, parallel, de novo plaque formation study design. The chlorhexidine mouthrinse was significantly better than the others in plaque inhibition. The propolis- containing rinse was marginally better than the negative control, but this difference was not significant.

[lxxxiii] ANALYSE DER BEDEUTENDSTEN PROPOLISVARIETÄTEN

IN BRASILIEN

T. NAKASHIMA
N. NAKASHIMA

Seit 5 Jahren unternehmen die Verfasser empirische und Laboruntersuchungen mit Propolis aus allen Regionen Brasiliens. Die Verfasser bringen zum ersten Mal die Ergebnisse der in Japan und in Brasilien durchgeführten Laboranalysen mit den drei bedeutendsten Propolisvarietäten aus dem Süden, Südosten und Norden Brasiliens. Die vorherrschende Farbe dieser Varietäten ist rot, grün und hell-farbig. In Brasilien gibt es über 30 Propolisvarietäten. Die Verffasser führen die Anwendungsmöglichkeiten dieser drei Varietäten an und stellen die Hypothese auf, daß die Propolis der afrikanisierten Bienen eine unterschiedliche Zusammensetzung gegenüber der europäischen Bienen aufweist. So z.B. ist der Pollen in der Propolis der afrikanisierten Bienen in viel großerem Maße vertreten.
S. 526

[lxxxiv] Grupo de Pesquisa e Desenvolvimento de Biofármacos (BIOFAR), Universidade do Sul de Santa Catarina, UNISUL. Av. José Acácio Moreira, 787.Tubarão/SC CEP 88704-900 – Brasil.

Fone/fax (55) 48 621-3067. Email: niraldo@unisul.rct-sc.br // niraldo@excite.com

* Departamento de Pós Graduação, Universidade Bandeirante de São Paulo, São Paulo/SP – Brasil

** Departamento de Farmacologia, Universidade do Sul de Santa Catarina, Florianópolis/SC – Brasil.

[lxxxv] Abstract

Propolis is a natural product produced by bees. In the folk medicine propolis is used in the treatment of respiratory diseases. The objective this work is to evaluate the effect of ethanolic extract of propolis (EEP) on the smooth muscle of guinea pig isolated trachea, and to investigate its pharmacological mechanisms of action. Guinea pigs (both sexes, 250-400g) were killed by cervical dislocation, trachea was removed and cut in six transversal segments containing three rings. These preparations were suspended in a organ bath containing Krebs-Henseleit at 37ºC, pH 7.4, and gazed with a mixture of O₂ 95% and CO₂ 5%. The isometric relaxant responses were measure by means of force displacement transducer (TRI-201) coupled to a Polygraph 6006 (Letica Scientific Instruments). Incubation of the phenolic compounds isolated from propolis, in the bath, produced a relaxant response in the guinea pig isolated trachea. The EEP (10^-10-10^-6g.mL^-1) induced a relaxant effect in the preparations with or without epithelium, precontracted by histamine, with CE50 means 4.4 (1.6-11.9) ng.mL^-1 or 20.6 (5.9-71.1) m g.mL^-1 respectively. Presence of KCl 40 or 80mM in the medium produced a inhibition of 26.0 (±9.0)% or 92.8 (±2.73)%, respectively. The addition of TEA (100 mM) or 4-AP (10mM) inhibited 31.0 (±9.8) or 28 (±1.5)% of relaxant response of EEP. Apamin (0.1 mM or 0,3 mM) inhibit 65.0 (±2.9) or75.0 (±3.5), while charybdotoxin (0,1 mM) inhibit 60.0 (±5.5)% and glibenclamide (1 or 3 mM) inhibit 57.0 (±4.0) or 58.0 (±8.5)%. Iberiotoxin (0.1 mM) produced a rightward displacement of 1.4 times in the relaxant response curve to EEP. w-conotoxin GIVA (0.1mM) and capsaicin (1 mM) did not affect the relaxant response curve induced by EEP. Furthermore, D-p-Cl-Phe6,Leu17[VIP] (0.1 mM) inhibited 55.0 (±5.7)% and propranolol caused a parallel displacement to the right of 250 times in the relaxant curve to EEP. L-NOArg (10 or 100 mM) inhibited 48.0 (±6.3)% or 49.0 (4.6)%, while methilene blue (10mM) inhibit 37.4 (±5.8)%, or ODQ (1 mM) produced a displacement to the right 0.65 times in the relaxant effect of propolis in the guinea pig isolated trachea. Take together these results shown that multiples mechanisms of actions are involved in the relaxant propolis-induced response on the smooth muscle of guinea pig isolated trachea. These results, also indicated that the principal propolis relaxant signaling pathway involved in response include direct activation of potassium channels, modulation of VIP or b-adrenoceptors receptors and the nitric oxide pathway.

[lxxxvi] Okonenko, L. B. (1986) – Propolis as an inhibitor of free radical lipid oxidation in salmonellosis,
in Vopr Med Khim,32(3), pp.45-48 (abstract).

Lipid peroxidation was activated in salmonellosis. Content of hydroperoxides and malonic dialdehyde was increased in mice liver tissue. At the same time, the activity of antioxidative enzymes was altered. Continuous administration of propolis stabilized lipid peroxidation, thus suggesting that the substance could be used as a drug in medicine.

[lxxxvii] UTILIZATION OF PROPOLIS IN THE TREATMENT OF LINGERING FORMS

OF INTESTINAL INFECTIONS IN CHILDREN

39 S.M. OMAROV, Z. M. OMAROVA

(RUSSIA)

The constant interest of researchers in new methods of prophylaxis and treatment of gastrointestinal diseases is caused by a high frequency of these diseases and by the absence of effective methods of control.

The application of apitherapeutics in the prophylaxis and treatment of gastrointestinal diseases is based on the anti-inflammatory, analgesic, immunogenous and antioxidant effects of these products.

Acute intestinal infections in children are often of the lingering type. They results in disbacteriosis, malabsorption and hypopolyvitaminosis.

The destruction of enterocytes, the modification of the normal intestinal flora, the breakdown of the system of general and local immune responses are typical of the intestinal inflammation. Therefore, it is very important to find a drug which is able to normalise the immunity.

Propolis is a product that enhances immunity in children with intestinal infections. To prove this, we effected an experiment using 10% propolis solution.

To determine the immune response of the organism, we studied the spontaneous migration of leukocytes and the level of serum fibronectin, that is a non-specific opsonin.

48 children, aged between 2.5 months and 3 years, were observed.

In 35 children (75%), the effect was positive: after they were treated with propolis, the intoxication symptoms disappeared, the frequency of stools decreased and the children put on weight. In the group of children who did not take propolis, only 8 patients (40%) showed a good clinic response.

Thus, we may conclude that propolis improves the defensive capacity of the organism and, therefore, may be prescribed to treat patients with gastroduodenal ulcer. Besides, propolis may also be used to treat children with intestinal infections.

p.124

[lxxxviii] APITHERAPIEERZEUGNISSE FÜR NASEN-, OHREN- UND HALSLEIDEN

Im Rahmen des Apitherapie-Arzneizentrums von Bukarest bewiesen wir in der Behandlung von Nasen-, Ohren- und Haisleiden die hohe therapeutische Wirksamkeit der Bienenprodukte, die wir bei akuten und chronischen Entzündungen der oberen Atemwege verwendet haben : Rhinopharingitis, Rhinopharingolaringitis, Rhinopharingoamigdalitis, Rhinosinusitis, Mittelohrentzündungen, usw.

Zur Förderung der Reaktion der Patienten wurden Propolis und die anderen Bienenerzeugnisse (Honig, Pollen, Weiselfuttersaft) sowohl intern als auch extern angewendet, wie Tropfen, Aerosol, Gurgeln, Bepinseln, Auftragen von Salben, usw. Außerdem wurde auch allgemein mit konditionierten Apitherapieprodukten behandelt (Dragées, Lösungen, Sirup, usw.).

Die Medikamente stammten aus dem Forschungslabor für Apitherapie. Sie sind alle vom Institut für Staatliche Kontrolle der Arzneimittel und Pharmazie-forschungen des Gesundheitsministeriums unseres Landes bewilligt.
S. 527-528

[lxxxix] Ministerio de Salud Publica. Facultad de Ciencias Medicas. “MARIANA GRAJALES COELLO”, HOLGUIN, Cuba.

[xc] Con la finalidad de contribuir a la aplicación de la propoleoterapia en las diferentes alteraciones pulporradiculares se realizó un estudio cuasiexperimental con muestra de 62 pacientes, los cuales asistieron a la consulta de Atención Primaria del Departamento de Estomatología en la Policlínica “Mario Gutierrez Ardaya” del Municipio Holguín en el período correspondiente del primero de Enero al treinta de Junio del año 1999 a los cuales se les había indicado tratamiento pulporradicular.

Los datos fueron recogidos en un formulario confeccionado al efecto, además de la Historia Clínica de Endodoncia evolucionando con intervalo de siete días. Se determinó la efectividad de la tintura de propóleos al 5% en los pacientes tratados, con resultados significativos a favor de los que curaron. Se valoró el tiempo promedio para concluir el tratamiento, el cual se logró entre los siete y catorce días de iniciado el mismo. No se detectaron cambios en la coloración del diente tratado, sólo se encontraron 5 pacientes con cambios en la coloración del diente antes de iniciar el tratamiento, aspecto que atribuimos a la alteración crónica que ocasionó la muerte pulpar. No se observaron cambios durante el tratamiento ni al finalizar el mismo. No se produjeron reacciones adversas.

Por los resultados obtenidos se recomienda el uso de la tintura de propóleos al 5% como cura medicamentosa intraconducto en el tratamiento pulporradicular, así como continuar investigando la posibilidad de utilizarlo durante todo el tratamiento en diferentes formas farmacéuticas e intentar realizar la obturación definitiva con conos elaborados a partir de este apifármaco de magnificas propiedades.

[xci] Universidade Estadual de Campinas – UNICAMP, Faculdade de Engenharia de Alimentos, Caixa Postal 6177, CEP 13081 – 970, Campinas – SP, Fone: 55-19-788-7055, Fax: 55-19-788-7890. Email: ykpark@fea.unicamp.br

[xcii] We have collected 500 propolis samples which were collected by Africanized Apis mellifera in Southern, Southeastern, Central western, and Northeastern Brazil. The respective samples were extracted with ethanol. The ethanolic extracts of propolis (EEP) were analyzed by physicochemical methods such as appearance of EEP, measurement of absorption spectra by UV-spectrophotometry, reversed phase-thin layer chromatography (RP-HPTLC), reversed phase high performance liquid chromatography (RP-HPLC) and then the EEPs were evaluated their physiological activities such as antioxidant activity, antimicrobial activity, assay of cytotoxic activity to cancer cells, and HIV-growth inhibition assays. In accordance with results of EEP appearance, UV-absorption spectra, RP-HPTLC, and RP-HPLC, the propolis were classified as 12 groups. Among 12 groups of propolis, five groups of propolis were collected from Southern Brazil, whereas six groups of propolis were collected from Northeastern Brazil. Furthermore, one group of propolis was found in Southeastern Brazil. It was found that the variety of propolis is depending on plant ecology. Although rarely exceptional propolis was found in spite of geographic locations, these propolis were not included in this study. Physiological activities for 12 groups of propolis were also variables, depending on geographical location. This is due to fact that the compositions of propolis are depending on the compositions in plants.

[xciii] VERWENDUNG DER BIENENPRODUKTE IN AUGENLEIDEN

M.P. POPESCU
Dana Alexandru POPESCU
M. POPESCU
Elena PALOS
Filofteia POPESCU (Romania)

Produkte mit Honig, Weiselfuttersaft und Propolis wurden lokal und im allgemeinen bei Behandlung von Augenleiden angewendet. Mit Apitherapieprodukten wurden 492 Kranke behandelt, die periodisch zwischen 5 und 10 Jahren untersucht wurden. In 383 Fällen konnte die Sehschärfe beibehalten werden, beim Rest der 109 Kranken wurde kein Erfolg verzeichnet. Bei einer Kontrollgruppe von 162 Fällen mit üblicher Behandlung waren nur 32 Fälle erfolgreich.
S. 529

[xciv] Przybylski,J.; Scheller, Stanislaw (1985) (Poland) – Early results in the treatment of Legg – Calve – Perthes disease using intra-articular injections of aqueous propolis extract,
in Z – Orthop., Mar-Apr., 123 (2), pp.163-67 (abstract).

Authors presented results in conservative treatment of 54 cases of hip joint with aseptic necrosis of thigh bone. In 22 hips, excluding the typical conservative treatment, APE injections were given. However, in the remaining 32, different forms of relieve were used. The obtained results in the first group (A) confirm the purpose of enrichment in conservative treatment by adapting intra- articular injections of APE especially in advanced stages of necrosis (III-IV period of illness) and also in those whose parents did not express their consent on surgery in the early stage of the illness.

[xcv] Rao, C. V.; Desai, D.; Rivenson, A.; Simi, B.; Amin, S.; Reddy, B. S. (1995) – Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate,
in Cancer Res, 55(11), pp.2310-15 (abstract).

Previous studies from this laboratory have established that caffeic acid esters present in propolis, a natural resin produced by honey bees, are potent inhibitors of human colon adenocarcinoma cell growth, carcinogen-induced biochemical changes, and preneoplastic lesions in the rat colon. The present study was designed to investigate the chemopreventive action of dietary phenylethyl-3-methylcaffeate (PEMC) on azoxymethane-induced colon carcinogenesis and to examine the modulating effect of PEMC on phosphatidylinositol-specific phospholipase C (PI-PLC), phospholipase A2, lipoxygenase (LOX), and cyclooxygenase activities in the colonic mucosa and tumor tissues in male F344 rats. At 5 weeks of age, groups of rats were fed the control (modified AIN-76A) diet, or a diet containing 750 ppm of PEMC. At 7 weeks of age, all animals except those in the vehicle (normal saline)-treated groups were given 2 weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. All groups were maintained on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Both colonic mucosa and tumors were analyzed for PI-PLC, phospholipase A2, cyclooxygenase, and LOX activities. The results indicate that dietary administration of PEMC significantly inhibited the incidence and multiplicity of invasive, noninvasive, and total (invasive plus noninvasive) adenocarcinomas of the colon (P < 0.05-0.004). Dietary PEMC also suppressed the colon tumor volume by 43% compared to the control diet. Animals fed the PEMC diet showed significantly decreased activities of colonic mucosal and tumor PI-PLC (about 50%), but PEMC diet had no effect on phospholipase A2. The production of 5(S)-, 8(S)-, 12(S)-, and 15(S)- hydroxyeicosatetraenoic acids via the LOX pathway from arachidonic acid was reduced in colonic mucosa and tumors (30-60%) of animals fed the PEMC diet as compared to control diet. PEMC had no effect on the formation of colonic mucosal cyclooxygenase metabolites but inhibited the formation in colonic tumors by 15-30%. The precise mechanism by which PEMC inhibits colon tumorigenesis remains to be elucidated. It is likely that the chemopreventive action may be related, at least in part, to the modulation of PI-PLC-dependent signal transduction and LOX- mediated arachidonic acid metabolism.

[xcvi] BEHANDLUNG VON LEIDEN DER WEIBLICHEN GESCHLECHTS-

ORGANE MIT APITHERAPIEERZEUGNISSEN

S. ROMAN
Elena PALOS
Cristina MATEESCU (Romania)

Verfolgt wurde bei 137 Kranken die Wirkung der Propolis in entzündlichen Distrophieerkrankungen des weiblichen Geschlechtsapparats. Die in 5 Gruppen ein-geteilten Patientinnen wurden außer der üblichen Medikamentation auch mit Propolis behandelt (Propoliszäpfchen, Propolissalbe, Propolistinktur, Propolisspray). Nach 25-35 Tagen erhielten wir in 53 Fällen sehr gute Ergebnisse, in 24 Fällen gute und in 28 Fällen zufriedenstellende. Nur in 16 Fällen hatten wir keinen Erfolg.

Daraus geht hervor, daß die Bienenprodukte die antiseptische, antifungizide und antitrichomoniasische Wirkung der üblichen Arzneimittel unterstützen und zu einer schnelleren Heilung verhelfen.

S. 530

[xcvii] Samoliuk, V. A. (1995) – The indices of the antioxidant system and the status of the cerebral blood supply in patients with an ischemic stroke on apitherapy,
in Lik Sprava(1-2), p.68 (abstract).

It has been established that the use of apitherapy (pollen and propolis) to treat patients with ischemic insults leads to deeper positive shifts in indices of the antioxidant system and brain blood supply. This, in its turn, makes for rapid and complete restoration of disturbed and lost functions of the patients’ organism.

[xcviii] TWO DECUBITUS ULCERATIONS PATIENTS, IN CRITICAL CONDITION,

TREATED WITH HONEY AND PROPOLIS

459 Rosa MORFI SAMPER, A. PEREZ PINEIRO, Marta CABALLERO, J. RAMOS, L.A. CUZA, Teresa GIRAL RIVERA

(CUBA)

In the specialised literature, the fact that propolis is used to treat a wide range of skin diseases (dermatitis, eczema, herpes, various wounds, etc.), as it stimulates a rapid recovery and offers protection against infections, is well-known. Honey has also been used in traditional medicine to treat skin injuries. In the present report, we effected a clinic experiment in which we used honey and propolis to treat decubitus ulceration’s. It was demonstrated that this treatment is highly effective against decubitus ulcers. p.123

[xcix] Aluna de Mestrado em Ciências Farmacêuticas, Universidade São Francisco, Bragança Paulista, SP. Endereço: Rua Mario Gianeschi 533, V. Gilglio, Atibaia, SP, Brasil, telefone 011- 484-5871.
Email: franksawaya@amhanet.com.br

[c] Coordenador do Mestrado em Ciências Farmacêuticas, USF, Bragança Paulista , SP.

[ci] Professora da Universidade São Francisco, Bragança Paulista, SP.

[cii] Abstract
A própolis é uma resina coletada pelas abelhas para reforçar os favos e manter a assepsia da colmeia. Devido a sua atividade antimicrobiana já era utilizada pelos egípcios e pelos gregos para cuidar de feridas e supurações. Hoje em dia é encontrada na composição de diversas formulações e freqüentemente utilizada pela população para cuidar de afeções causadas por microorganismos.

Este trabalho tem dois objetivos: 1. avaliar a atividade antimicrobiana de amostras de própolis extraídas por diferentes métodos, visando comparar sua atividade frente a diferentes microorganismos; 2. comparar diferentes técnicas microbiológicas de avaliação da atividade antimicrobiana. As cinco técnicas usadas foram a bioautografia, diluição seriada em tubos e em placas, difusão em placas usando discos de papel e cilindros de aço. As amostras de própolis foram extraídas variando as concentrações de etanol e água do solvente extrator, o tempo e temperatura de extração e o fator luz; obtendo um total de 26 amostras de própolis a partir de 3 lotes de própolis bruta. Para avaliar estas amostras foram utilizadas 16 cepas de bactérias (gêneros Staphylococcus e Streptococcus) e 18 cepas de leveduras ( gênero Candida). Para a avaliação estatística dos resultados foi usado o método de análise exploratória de dados multivariados.

Comparando os resultados obtidos nos diferentes métodos de avaliação foi possível observar quais os fatores que afetaram a composição e atividade antimicrobiana das amostras testadas. Os fatores luz e tempo de extração não afetaram a atividade antimicrobiana das amostras de própolis, porém, o solvente usado na extração das amostras de própolis afetou a composição e consequentemente a atividade antimicrobiana destas. Os melhores resultados frente a bactérias foram obtidos com amostras extraídas com concentrações de etanol entre 50 e 70%.
Método de avaliação microbiológica usado também afetou os resultados, pois os testes de difusão em placas são diretamente influenciados pela hidrossolubilidade dos componentes das amostras de própolis, dando resultados favoráveis às amostras mais hidrossolúveis. Os métodos de bioautografia, diluição seriada em tubos e em placas, aparentemente não foram afetadas por este fator, fornecendo resultados confiáveis.
Key words: Própolis, atividade antimicrobiana, métodos de extração, métodos de avaliação microbiológica, bioautografia.

[ciii] Scheller, Stanislaw; Szaflarski, J.; Tustanowski, J.; Nolewajka, E.; Stojko, A. (1977) – Biological properties and clinical application of propolis. I. Some physico-chemical properties of propolis,
in Arzneimittelforschung, 27 (II)(4), pp. 889-90 (abstract).

The presence of 19 elements has been shown in the ethanol extracts of propolis (EEP). Three fractions have been obtained by filtration through a structural gel that did not show an initial antibacterial activity when investigated separately. Fractions 2 and 3 joined together have regained this activity. EEP solutions maintain their anitbacterial activity in acidic or neutral pH. Insensitivity of EEP solutions on temperature of 75 degrees C for 30 min has been found.

[civ] Scheller, Stanislaw; Tustanowski, J.; Kurylo, B.; Paradowski, Z.; Obuszko, Z. (1977) – Biological properties and clinical application of propolis. III. Investigation of the sensitivity of Staphylococci isolated from pathological cases to ethanol extract of propolis (EEP). Attempts on inducing resistance in laboratory Staphylococcus strain to EEP,
in Arzneimittelforschung, 27(7), pp.1395 (abstract).

Staphylococci isolated from pathological material exhibited a reduced sensitivity to ethanol extract of propolis (EEP) in 90% of cases. No cross-resistance of the staphylococci to EEP and to any commonly used antibiotics was found. The induction of resistance to EEP in laboratory strain of Staphylococcus aureus (Oxford 209 P) can be achieved already after serial passages on nutrient media containing EEP. Culturing Staphylococcus resistant to EEP in an environment devoid of this compound caused a remission to sensitivity of the strain investigated.

[cv] Scheller, Stanislaw; Nolewajka, E.; Panasiewicz, M.; Dziekanowska, D.; Tustanowski, J.; Stojko, A. (1977) – Biological properties and clinical application of propolis. IV. The action of ethanol extract of propolis (EEP) on cells cultured in vitro,
in Arzneimittelforschung, 27(8), pp. 1547-8 (abstract).

An increase of total cell number was shown in the cell culture in vitro under the influence of ethanol extract of propolis (EEP). Addition of EEP to the nutrient medium of the cells caused a strong activation of mitoses. Besides, distinctly intensified metabolism of these cells expressed by a strong activation of NADH2-reductase was also observed.

[cvi] Scheller, Stanislaw; Stojko, A.; Szwarnowiecka, I.; Tustanowski, J.; Obuszko, Z. (1977) – Biological properties and clinical application of propolis. VI. Investigation of the influence of ethanol extracts of propolis (EEP) on cartilaginous tissue regeneration,
in Arzneimittelforschung, 27(11), pp. 2138-40 (abstract).

Dressing of artificially formed losses of the cartilaginous tissue with the preparation containing ethanol extract of propolis (EEP) caused acceleration of regenerating processes in the lesioned cartilage. EEP inserted into the joint is well tolerated.

[cvii] Scheller, Stanislaw; Tustanowski, J.; Felus, E.; Stojko, A. (1977) – Biological properties and clinical application of propolis. VII. Investigation of immunogenic properties of ethanol extract of propolis (EEP),
in Arzneimittelforschung, 27(12), pp..2342 (abstract).

Under experimental conditions parenteral administration of ethanol extract of propolis (EEP) solutions to rabbits induced no synthesis of antibodies as investigated by means of ring precipitation, double diffusion gel precipitation and complement fixation test.

[cviii] Scheller, Stanislaw; Ilewicz, L.; Luciak, M.; Skrobidurska, D.; Stojko, A.; Matuga, W. (1978) – Biological properties and clinical application of propolis. IX. Experimental observation on the influence of ethanol extract of propolis (EEP) on dental pulp regeneration,
in Arzneimittelforschung,28(2), pp. 289-91 (abstract).

The use of ethanol extract of propolis (EEP) on injured dental pulp results in the stimulation of regenerative processes. A reduction of disorders of the circulatory system is observed, inflammatory and degenerative processes are also reduced.

[cix] Scheller, Stanislaw; Luciak, M.; Tustanowski, J.; Koziol, M.; Obuszko, Z.; Kurylo, B. (1978) – Biological properties and clinical application of propolis. XI. Histophathological analysis after intravenous application of ethanol extract of propolis (EEP),
in Arzneimittelforschung, 28(9), pp. 1594-95 (abstract).

Mice were given i.v. injections of water solutions of ethanol extract of propolis (EEP) over a varying period of time. Some of the animals were sacrificed immediately following the last injection and some within 2-4 weeks after the last injections. Internal organ samples were taken and underwent a microscopic examination. Insignificant pathological changes in the liver were observed. These changes were transient and regressed within 2-4 weeks after the application of EEP.

[cx] Scheller, Stanislaw; Krol, W.; Swiacik, J.; Owczarek, S.; Gabrys, J.; Shani, J. (1989, 1991) – Antitumoral property of ethanolic extract of propolis in mice-bearing Ehrlich carcinoma, as compared to bleomycin,
in Z Naturforsch (C), 11, 44(11-12), 1989, pp.1063-65 (abstract);
in Kaal, 1991, p.27-29 (***).
Antitumoral effect of ethanolic extract of propolis (EEP) was demonstrated in mature mice-bearing Ehrlich carcinoma. Survival rate after EEP treatment was compared to that of bleomycin, given alone or in combination every two days for 36 days and followed up for 14 additional days. The survival rate at 50 days was 55% after EEP and 40% after bleomycin, while all the mice-treated with EEP + bleomycin combination demonstrated shorter survival than the controls. It is concluded that while the in vivo activity of bleomycin is reduced in the presence of cytochrome-C-reductase inhibitors (like some of the EEP components are), the antitumoral property of EEP in the tumored animal model studied is significant and lasting.

[cxi] Shub, T. A.; Kagramanova, K. A.; Voropaeva, S. D.; Kivman, G. Ya (1981) – Effect of propolis on Staphylococcus aureus strains resistant to antibiotics,
in Antibiotiki, 4, 26(4), pp.268-71 (abstract).

The activity of propolis and its combinations with antibiotics against antibiotic resistant strains of Staphylococcus aureus was studied. It was found that staphylococcae strains resistant to benzylpenicillin, tetracycline and erythromycin were mainly sensitive to propolis. It is concluded that there was synergism in the effect of propolis and antibiotics with respect to antibiotic resistant strains of Staphylococcus aureus.

[cxii] Siro, B.; Szelekovszky, S.; Lakatos, B.; Mady, G.; Szathmari, E.; Karanyi, Z. (1996) – Local treatment of rheumatic diseases with propolis compounds (see comments),
in Orv Hetil, 137(25), pp.1365-70 (abstract).

The authors conducted a single blind, placebo controlled local therapy trial on a total of 190 patients involving the use of materials (i) topically and (ii) by iontophoresis for pain and/or inflammation of the organs of movement. The materials used comprised of the following: (i) purified propolis and propolis saturated with antiinflammatory trace metal elements and (ii) propolis saturated with trace metal elements and poplar bud ointment saturated with trace metal elements also. Both methods of application using all the three preparations significantly improved symptoms. The preparations saturated with metallic ions were more effective. The mild effect of the placebo treatment is explained by the treatment procedure itself.
Side effects were not observed.

[cxiii] Cátedra de Química Orgánica y Biológica – Facultad de Ciencias Agrarias – Universidad Nacional del Nordeste. Sargento Cabral 2131 – (3400) – Corrientes – República Argentina. Email: avallejos@agr.unne.edu.ar

[cxiv] Responsable a cargo del Centro de Investigaciones Apícolas – Facultad de Ciencias Agrarias – Universidad Nacional de Santiago del Estero – República Argentina.

[cxv] Director Nacional del Proyecto Integrado de Desarrollo Apícola – Instituto Nacional de Tecnología Agropecuaria – Estación Experimental Famaillá – República Argentina.

[cxvi] En general es aceptada la existencia de una amplia variabilidad en la composición de los propóleos, debida entre otras cosas a las diferentes fuentes vegetales, ubicación en la colmena, región fitogeográfica, etc. De los 19 minerales encontrados en el propóleos, uno de los más importantes es el Cinc por su rol en las propiedades antiinflamatorias y antioxidantes.

El objetivo del presente trabajo fue realizar una primera aproximación a la determinación de la concentración del elemento Cinc en los propóleos del Noreste Argentino. Se trabajo con 17 muestras procedentes de las provincias de Corrientes, Chaco y Misiones, obtenidas mediante el uso de mallas tipo mosquitero y por raspado, realizándose cuatro determinaciones por muestra mediante Espectrofotometría de Absorción Atómica.

Los resultados obtenidos indican una amplia variabilidad en el contenido de Cinc, con valores que fluctuaron entre 10,29 mg/kg^-1 y 105,84 mg/kg^-1. Dentro de un mismo apiario se encontraron resultados más homogéneos en el propóleos obtenido mediante mallas (30,77 a 58,80 mg/kg^-1) que en el de raspado (11,66 a 64,82 mg/kg^-1). Para una misma colmena se encontró mayor concentración de Zn en el interior de la colmena que en el propóleos de la piquera.

Si bien es necesario continuar con los trabajos, los resultados obtenidos permiten inferir que la concentración de Cinc del propóleos se encuentra influenciada no solo por la región fitogeográfica, sino también por el método de extracción y la zona de la colmena.

[cxvii] Stangaciu Stefan (1998) (Romania) – Cuidados Para La Produccion Y Extraccion De Propoleos,
in Espacio Apícola Nº 33, junio, páginas 24 a 29.

A diferencia de la producción de miel, la producción de propóleos precisa de

cuidados mucho más estrictos.

También, de acuerdo a la calidad, pureza y condiciones de recolección del

mismo el precio varía sustancialmente.

De allí que, así como nos parece importante hacernos un planteo a partir de

lo indispensable en la producción de miel como producto alimenticio y para

salvaguardar el recurso económico de miles de apicultores en la Argentina,

no descuidamos la perspectiva del «laboratorio natural» que es la colmena.

Por tanto, no descuidamos la excelencia que se puede alcanzar en la

recolección, por ejemplo de propóleos, por la trascendencia y proyección

que éste producto tiene para la salud humana, como un medicamento de

excepcionales propiedades.

Con este objetivo, luego de un brevísimo cruce que a penas fue un saludo en

Bélgica y una posterior relación epistolar más profunda y concreta,

invitamos a Stefan Stângaciu, doctor en medicina a cargo del laboratorio

DAO Ltd. en Constanta, Rumania, (Asociación de Medicina Natural sin

Fronteras), miembro de la comisión permanente de Apiterapia de Apimondia y

de sendas sociedades apiterápicas de Estados Unidos y Europa, a disertar en

la Expo-Apícola San Francisco.

A decir verdad, en principio Stefan tenía una vaga idea de venir a fines de

marzo (ESPACIO APICOLA Nº31) pero, a partir de la publicación del

mencionado reportaje los organizadores de su visita a Buenos Aires

concretaron y pospusieron el viaje y esto nos permitió que disertara, por

primera vez en la Argentina, para un grupo de más de 400 apicultores en la

«6ª Feria y Jornadas de Apicultura del Centro de la República» Expo-Apícola

San Francisco’98.

El Dr. Stângaciu dejó en nuestra editorial importante material que

oportunamente iremos publicando o comentando, un libro y un par de

artículos sobre apiterapia, pero nos pareció ideal transcribir en esta

ocasión la disertación que nos brindó en la expo, el domingo 10 de mayo

próximo pasado, sobre «Cuidados en la Recolección de Propóleos» ya que se

trata de un aporte técnico sobre manejo de apiario que nos parece muy

importante.

Es muy importante tener propóleos de alta calidad para tener un buen

mercado. Yo sé que en la Argentina la Medicina Naturista no está muy

desarrollada y que la escuela tradicional de medicina es muy fuerte aquí.

Ahora para poder desarrollar bien este nuevo mercado, a partir del

propóleos, deben instrumentarse conocimientos mucho más elevados para que

éste sea de muy buena calidad.

Hay que tener en cuenta importantes principios en la recolección de

propóleos.

ASEPSIA.-En primer término se debe tratar al propóleos como a un bebé.

Deben tener mucho cuidado y todo debe ser muy aséptico. El apicultor debe

ser como un cirujano. Las manos deben ser esterilizadas para trabajar o

usar guantes esterilizados y todos los envases en los que se coloca el

propóleos deben ser esterilizados.

INOCUIDAD.- Otro principio es que el propóleos debe ser limpio y las

colmenas deben estar ubicadas en zonas donde no haya aplicación de químicos

(agroquímicos) y no haya ningún tipo de contaminación. Es muy importante

que el colmenar esté alejado de las carreteras por la posible contaminación

de plomo.

FOTOSENSIBLE.- Otro principio es que el propóleos debe estar protegido de

la luz. El propóleos contiene sustancias activas que son destruídas por la

acción de la luz. Es importante entonces que no esté expuesto por mucho

tiempo a la acción de la luz. La recolección debe ser rápida, no estamos

diciendo que haya que hacerlo de noche, sino simplemente que no dejemos el

propóleos expuesto a la luz por un tiempo prolongado. Los pigmentos de las

plantas protegen estas sustancias activas de la radiación solar; fuera de

las plantas, hay que proteger al propóleos de esa radiación.

TERMOSENSIBLE.- También hay que proteger al propóleos de una temperatura

alta. Podemos decir que el propóleos es un producto viviente, porque

contiene un 5% de polen y el polen es una parte viviente. En el

procesamiento del propóleos no se lo puede exponer a más de 40ºC, de lo

contrario se destruye la vida del propóleos.

Durante el trabajo con las abejas no se deben usar tratamientos químicos,

especialmente contra la varroa, porque estas sustancias químicas pueden

contaminar el propóleos. En los últimos tres años se ha probado que se

puede controlar la varroa con métodos naturales basados en el uso de

aceites aromáticos. Estos aceites son sacados de las plantas, ellas

producen estos aceites desde hace miles de años, para protegerse de

parásitos, microbios, virosis y hongos.

El ácido nicotínico también es bueno para combatir la varroa, como así

también algunas prácticas energéticas muy propias de la medicina china.

Si se utilizan tratamientos químicos para controlar la varroa es imperativo

sacar el propóleos antes de aplicar cualquier tratamiento.

En la colmena se tienen varios productos que son dinámicos. La elaboración

de la miel es rápida y entonces las sustancias químicas pueden ser

rápidamente eliminadas, pero el propóleos y la cera son sustancias

estables. Entonces la residualidad por ejemplo del fluvalinato o el amitraz

en el propóleos perdura. Para producir propóleos preferentemente hay que

partir de colmenas, núcleos o paquetes de abejas sin tratamiento alguno.

Una prescripción para el control del varroa es el uso de los siguientes

aceites esenciales naturales:

Tomillo,

Eucalipto,

Menta (la más común: Mentha piperita),

Romero y

Lavanda.

Estos aceites pueden combinarse con la miel, hacer un te o hacer un jarabe

y alimentar con él a las abejas. Por la trofalaxis los aceites esenciales

se distribuyen en forma uniforme en toda la colmena y la eficacia en el

control asciende a un 90 o 95%. No se acerca al 100% como los químicos,

pero se puede usar en forma permanente en cualquier época del año, sin

contaminar. Si se utiliza lavanda o menta, la miel tendrá un aroma

particular.

La dosificación de estos productos es muy flexible, se pueden usar 15 gotas

en unos 70 gr. de miel. Hay que prestar atención si las abejas aceptan o no

esta mezcla y si hay dificultades se la puede diluir con más miel.

Si a ustedes no les gusta este aroma en la miel, deben hacer la cosecha

antes de la aplicación de los aceites esenciales.

Para recolectar un propóleos de excelente calidad tampoco debe usarse el

ahumador. El humo contamina el propóleos. Existe en la actualidad un

producto alemán, aceite de la flor del clavel, que a las abejas no les

gusta y huyen. Se aplican dos gotas en un dispositivo que con un ventilador

difunde el aroma del aceite dentro de la colmena y las abejas salen. Es

100% biológico y no contamina.

Otro punto importante en la producción de propóleos es usar colmenas que no

estén pintadas con pinturas sintéticas y que los apicultores estén bien de

salud, sin resfríos u otra afección particularmente respiratoria o

infecciosa para no contaminar el propóleos.

Lo ideal es trabajar en un grupo, una persona puede dedicarse a la

recolección del propóleos y otro que esté en un lugar esterilizado para la

manipulación del mismo. La persona que hace el trabajo en las colmenas no

puede ingresar a este lugar porque su vestimenta puede incorporar

suciedades. Esto es lo ideal. En Francia quienes trabajan de esta manera

alcanzan el doble del precio en sus productos.

Volviendo a las técnicas de recolección existe el raspado y el uso de las

trampas. Los dos métodos tienen ventajas y desventajas. Cuando utilizan una

herramienta para raspar el propóleos que se obtiene es de muy buena

calidad, con alto contenido de resinas (ver ESPACIO APICOLA Nº32, trabajos

del CEDIA), pero es probable incorporar astillas y restos de abejas muertas

y eso no es conveniente. Quienes utilizan trampas sacan un producto muy

límpio, sin restos de madera o abeja, pero este propóleos tiene un

porcentaje más elevado de cera de abejas. Si ustedes quieren producir mucho

propóleos, deben usar las trampas.

Es conveniente, cuando se recolecta el propóleos de trampa, dejar un 20% en

la trampa, esto permite hacer dos recolecciones en el verano y si trabajan

con abejas caucásicas éstas, genéticamente, son más propolizadoras. He

escuchado que en la zona de Mendoza hay varios apicultores que trabajan con

caucásicas.

Cuando retiran las trampas, las enrollan, las ponen dentro de un recipiente

hermético (lo ideal sería que esté al vacío), porque el aire produce

fenómenos de oxidación. Podría ser una bolsa de plástico negro de buena

calidad. Luego, lo más rápido posible se lo lleva a un freezer (-20ºC) y se

lo deja hasta que el propóleos esté bien duro. Para extraerlo de las

trampas se sacan las mallas del freezer y se los coloca sobre una mesada en

la que previamente se colocó un papel blanco límpio sobre el que se

torsionan las trampas para que caiga el propóleos. Así llegamos al

propóleos en bruto.

En el caso del propóleos proveniente de raspado, hay que retirar todos los

restos de astillas de madera, restos de abejas o cualquier otro elemento

que podamos distinguir extraño al propóleos mismo. Para ello podemos

colocar el polvo proveniente del raspado en agua, previamente esterilizada,

entonces las impurezas van a flotar. Luego estas impurezas se retiran con

un colador o un elemento similar.

El propóleos puede permanecer en el agua aproximadamente 24 horas y ya

tenemos un extracto acuoso de propóleos que es muy bueno, es como un té de

propóleos que se puede beber y es muy bueno para la salud.

Una vez que tenemos el extracto acuoso de propóleos dejamos que el polvo se

seque para pasar a una segunda etapa del proceso.

Se coloca este polvo ya deshidratado, seco, en alcohol de 70º a 96º durante

al menos dos semanas. Se debe agitar el frasco periódicamente, en forma

manual o con algún mecanismo adecuado. El alcohol extraerá los elementos

más importantes del propóleos. Este procedimiento se usa en el 95% de los

países. En Argentina y España se usa el Propilenglicol pero éste tiene

ventajas y a su vez desventajas. El Propilenglicol es un solvente que no es

dañino para la salud, permitiendo dárselo directamente a niños o personas

con alergias respecto del alcohol o sirrosis o problemas hepáticos. Sin

embargo el Propilenglicol no es eficaz para extraer todos los principios

del propóleos.

Después de las dos semanas se debe usar un sistema de doble filtro para

extraer una tintura, como cualquier otra tintura de especies botánicas. Se

trata de fórmulas milenarias. La mayoría de las corrientes médicas está de

acuerdo con el uso de estos extractos y no se animan a hablar mal de ellos.

Aún lo que queda en los filtros tiene también importantes propiedades y no

tenemos porque tirarlo a la basura. Es como tirar oro a la basura. Ese

residuo debe ser colocado nuevamente en alcohol durante uno o dos meses o

uno o dos años. Esto seguirá extrayendo principios del propóleos.

La primera extracción puede ser utilizada para muchísimas afecciones, la

segunda puede ser utilizada para esterilizar colmenas, particularmente

después de armar el material nuevo, dando un baño a todo el interior de ese

material. También podemos usarlo para uso personal, para curar heridas o

problemas de piel.

Entre un 1 y 2% de la población podría presentar alguna reacción alérgica

local, enrojecimiento o picazón, que no provoca ninguna afección. Quien

pudiera tener alguna de estas reacciones sólo con lavarse con agua o

alcohol elimina el problema.

Con la primera extracción acuosa de propóleos se realizan muchas

preparaciones. En Japón, una sola compañia, compra 80 tn de propóleos de

origen brasileño. Mendoza, que tiene muchos álamos, cuenta con un potencial

muy interesante para la producción de propóleos. Solamente allí se podrían

producir mil toneladas de propóleos. Ese propóleos en bruto puede

exportarse o mejor aún si se lo puede procesar.

Esta tintuta de propóleos que preparamos no tiene vencimiento, es como el

vino tinto, cuanto más estacionado es mejor (aclamación del público !!).

Para otros usos, fabricación de cremas o unguentos, esta tintura hay que

evaporarla, sin sobrepasar los 40º revolviéndolo para acelerar el proceso

obteniendo así una pasta base.

En Cuba, donde estuve en febrero (ver nota pág. 30) se utiliza el propóleos

en una concentración al 5% con muy buenos resultados. Si ustedes quisieran

hacer una tintura de propóleos con una concentración del 30% deben diluir

40 gr. de propóleos en bruto en 60 gr. de alcohol.

NOTA EDITORIAL: En futuras publicaciones continuaremos brindando material.

[cxviii] Starzyk, J.; Scheller, Stanislaw; Szaflarski, J.; Moskwa, M.; Stojko, A. (1977) (Poland) – Biological properties and clinical application of propolis. II. Studies on the antiprotozoan activity of ethanol extract of propolis,
in Arzneimittelforschung, 27(6), Seite 1198-9.

Solutions of the ethanol extract of propolis (EEP) have shown a lethal effect on Trichomonas vaginalis in vitro. Similar lethal action was exhibited by EEP after a 24-h contact with Toxoplasma gondii.

[cxix] Steinberg, D.; Kaine, G.; Gedalia, I. (1996) – Antibacterial effect of propolis and honey on oral bacteria,
in Am J Dent, 9(6), pp.236-39 (abstract).

Purpose: To investigate the antibacterial properties of propolis and honey against oral bacteria in vitro and in vivo.
Materials and Methods: In vitro study: The antibacterial effects of propolis and honey on oral streptococci were determined using the broth method. Clinical study: The short-term antibacterial effect of propolis solution and honey on salivary total bacteria and Streptococcus mutans was tested in 10 volunteers. Results: Propolis demonstrated an antibacterial effect both in vitro on isolated oral streptococci and in the clinical study on salivary bacterial counts. Honey induced bacteria growth at low concentrations, while at high concentrations honey had an inhibitory effect on bacterial growth in vitro. Salivary counts of total bacteria and Streptococcus mutans were lower for 1 hour after application of honey. The antibacterial effect of the honey tested may be attributed to its osmolarity effect.

[cxx] Stojko, A.; Scheller, Stanislaw; Szwarnowiecka, I.; Tustanowski, J.; Ostach, H.; Obuszko, Z. (1978) – Biological properties and clinical application of propolis. VIII. Experimental observation on the influence of ethanol extract of propolis (EEP) on the regeneration of bone tissue,
in Arzneimittelforschung, 28(1), pp.35-37 (abstract).

Artificially induced bone tissue losses after the application of ethanol extract of propolis (EEP) showed an accelerated rate of ossification. The osteogenetic process was just about half as long as in the control group.

[cxxi] CHEMISCHE UND VERSUCHSUNTERSUNCHUNGEN

ZUR STANDARDISIERTEN VERWENDUNG DER PROPOLIS UND POLLENPRODUKTE IM APITHERAPIEZENTRUM VON KAMIANNA

A. STOJKO
J. STOJKO
H. OSTACH (Poland)

Zwischen 1984 und 1988 wurden im Apitherapiezentrum von Kamianna 4.573 Kranke mit EPR und PHP behandelt. Es handelte sich um folgende Krankheiten chronische Entzündung der Atemwege bei Kindern, Bronchialasthma bei Erwachsenen und Kindern, sklerotische Veränderungen der unteren Gliedrnaßen, Bürger-Krankheit, Geschwüre und Stoffwechselkrankheiten des Verdauungsapparats, Prostataentzündung, Hautentzündungen unterschiedlicher Äthiologie. 12 Tabellen veranschaulichen diese Fälle zusammen mit einer eingehenden Beschreibung der Diagnose, der Krankheitsdauer und der Behandlungsergebnisse.
S.542

[cxxii] CHEMISCHE UND VERSUCHSUNTERSUNCHUNGEN

ZUR STANDARDISIERTEN VERWENDUNG DER PROPOLIS UND POLLENPRODUKTE IM APITHERAPIEZENTRUM VON KAMIANNA

A. STOJKO
J. STOJKO
H. OSTACH (Poland)

[cxxiii] Strehl, E.; Volpert, R.; Elstner, E. F. (1994) – Biochemical activities of propolis-extracts. III. Inhibition of dihydrofolate reductase,
in Z Naturforsch (C), Jan-Feb. 49(1-2), pp.39-43 (abstract).

Ethanolic and aqueous extracts of the natural compound propolis indicate substantial antiinflammatory functions as well as antibiotic activities in vitro and in vivo. The exact mode of physiological or biochemical mechanisms responsible for the medical effects, however, is all but clear. The standardization on the basis of quantitative determination of prominent components of these extracts have been substituted recently by simple biochemical model reactions including photodynamic properties. In this communication we report on the inhibitory activity of an aqueous extract of propolis on the enzyme dihydrofolate reductase. This activity may at least partially be due to the content of caffeic acid, as revealed by HPLC chromatography and comparative activity tests of representative ingredients of the propolis extract. This result may explain some of the protective functions of propolis, similar to those shown for several “non- steroidal antiinflammatory drugs”, NSAIDs.

[cxxiv] Su, Z. Z.; Lin, J.; Grunberger, D.; Fisher, P. B. (1994) – Growth suppression and toxicity induced by caffeic acid phenethyl ester (CAPE) in type 5 adenovirus-transformed rat embryo cells correlate directly with transformation progression,
in Cancer Res, 54(7), pp.1865-70 (abstract).

The active component of the honeybee hive product propolis, caffeic acid phenethyl ester (CAPE), induces a selective growth suppressive and toxic effect toward cloned rat embryo fibroblast cells transformed by adenovirus type 5 (Ad5) or the Ad5 E1A transforming gene versus untransformed cloned rat embryo fibroblast cells (Z-z. Su et al., Mol. Carcinog., 4: 231-242, 1991). The present study was conducted to determine whether CAPE-induced growth suppression/toxicity was a direct result of expression of the Ad5 E1A and E1B transforming genes or a consequence of the action of these genes resulting in the transformed state. For this investigation we used somatic cell hybrids and 5- azacytidine-treated Ad5-transformed rat embryo cells that display different stages of expression of the transformed phenotype. This series of cell lines has permitted us to determine whether expression of the transformed state and the stage of transformation progression regulates CAPE sensitivity. Evidence is presented indicating that sensitivity to CAPE is directly determined by the state of expression of the transformed progression phenotype, as opposed to simply the expression of the Ad5 E1A and E1B transforming genes. These results provide further evidence that CAPE may represent a unique compound that can specifically target progressed transformed cells for growth suppression and toxicity. An understanding of the mechanism underlying this selective effect of CAPE could result in the identification of important biochemical pathways mediating cellular transformation and progression of the transformed state.

[cxxv] Su, Z. Z.; Lin, J.; Prewett, M.; Goldstein, N. I.; Fisher, P. B. – Apoptosis mediates the selective toxicity of caffeic acid phenethyl ester (CAPE) toward oncogene-transformed rat embryo fibroblast cells,
in Anticancer Res, 15(5B), pp.1841-8 (abstract).

The active component of the folk medicine propolis, caffeic acid phenethyl ester (CAPE), displays selective toxicity toward cloned rat embryo fibroblast (CREF) cells transformed by a spectrum of diverse acting oncogenes. Identification of the mode of action of CAPE should provide useful information for possible applications of this compound for cancer therapy. The present study uses a series of oncogene transformed, oncogene-reverted and CAPE-resistant oncogene transformed CREF cells to investigate the mechanism underlying the increased sensitivity of transformed cells to CAPE. A direct relationship exists between the cytotoxic effects of CAPE and the induction of DNA fragmentation and apoptosis. DNA degradation into nucleosomal fragments and apoptotic shifts in DNA cell cycle profiles occur in CAPE-treated CREF cells transformed by wild-type 5 adenovirus (Ad5), a mutant Ad5 (H5hr1), the wild-type Ad5 E1A transforming gene, v-src, Ha-ras and the human papilloma virus type 18 transforming genes (HPV-18). In contrast, untransformed CREF cells, human fibroblast expression library-induced morphological revertants of Ad5- and v-src-transformed CREF cells, and Krev-1 expressing revertant Ha-ras-transformed CREF cells are resistant to CAPE-induced toxicity and apoptosis. Similarly, mutant Ad5- transformed CREF cells selected by step-wise growth in increasing concentrations of CAPE are resistant to growth inhibition and apoptosis induced by CAPE. These findings indicate that expression of the transformed phenotype by rodent cells evokes sensitivity to CAPE induced toxicity through apoptosis. The acquisition of CAPE sensitivity in rodent cells is independent of the mode of action of the oncogenic agent. CAPE may prove useful as an antiproliferative agent in cancer cells transformed by mechanistically diverse acting oncogenes.

[cxxvi] Suchy, Henry (1978) (Poland) – Efficiency of propolis in the treatment of Trichomonas vaginalis – in vitro and in vivo experiments,
in the Third International Symposium on Apitherapy, Portoroz, Yugoslavia, 1978, p.160-61; French, p.161-62 (abstract); German, Russian and Spanish, p.162 (abstract).

Spanish abstract: Eficacia del propoleos como remedio tricomonicida, en ensayos in vivo e in vitro.

Resumen: La aplicación del propóleos en los casos de inflamación de la vagina y el cuello uterino, eliminó los síntomas de tricomoniasis, por lo tanto alentando las investigaciones acerca del efecto de las tabletas de uso vaginal con propóleos, fabricada por la firma Sanguisan A.G. de Zurich, en Trichomonas vaginalis, tanto in vitro como in vivo. Para el cultivo, emplearon un liofilizado de cultivo de T. vaginalis que luego adicionaron, en varias concentraciones (de 9,0 mg a 3,0 mg), al propóleos de las probetas de ensayo. El cultivo fue repartido entre 10 probetas. Después de 24 horas, ya no era posible encontrar formas vivas de Trichomonas en ninguna de las probetas de ensayo, salvo las probetas testigo. Después del empleo local de 30 mg de tabletas vaginalis Sanguisan, desaparecieron por completo los sintomas de inflamación de trichomonas de la vagina y el cuello uterino. Al cabo de 10 dias de terapia local, el examen de control puso de manifiesto la ausencia completa de T. vaginalis, tanto en el frotis, como en cultivo.

[cxxvii] Sud’ina, G. F.; Mirzoeva, O. K.; Pushkareva, M. A.; Korshunova, G. A.; Sumbatyan, N. V.; Varfolomeev, S. D. (1993) – Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties,
in FEBS Lett, 329(1-2), pp.21-24 (abstract).

Caffeic acid phenethyl ester, an active component of propolis extract, inhibits 5-lipoxygenase in the micromolar concentration range. The inhibition is of an uncompetitive type, i.e. the inhibitor binds to the enzyme-substrate complex but not to the free enzyme. Caffeic acid phenethyl ester also exhibits antioxidant properties. At a concentration of 10 microM, it completely blocks production of reactive oxygen species in human neutrophils and the xanthine/xanthine oxidase system.

[cxxviii] Szmeja, Z.; Kulczynski, B.; Sosnowski, Z.; Konopacki, K. (1989) – Therapeutic value of flavonoids in Rhinovirus infections,
in Otolaryngol Pol, 43(3), pp.180-84 (abstract).

The clinic evaluation of the Canadian pharmacologic agent “propolis” verified its value known from the literature in common cold infections. 50 persons were treated in ENT Clinic of Marcinkowski’s Medical Academy in Poznan during the 1987 year. The observed therapeutic effects were shortening of the disease duration. The regression of symptoms occurred in the first day of the therapy and the complete recovery followed in 1 day in 5 patients, in 2 day in 16, and in 3 day in 3. The placebo group has his full recovery in mean 4.80 days. In the therapeutic group the symptoms lasted 2.5 time shorter than in placebo one.

[cxxix] Facultad de Ciencias Veterinarias – Universidad Nacional del Centro de la Provincia de Buenos Aires.

Paraje Arroyo Seco s/n – (7000) Tandil – Buenos Aires – República Argentina.

TeleFax: 54 2293-422357/426667. Email: atabera@vet.unicen.edu.ar

Instituto Nacional de Tecnología Agropecuaria (INTA) – EEA Famaillá. Ruta Provincial 301. Km 32- (4132) – Padilla – Famaillá – Tucumán – Argentina.
E-mail: ebedas@inta.gov.ar ; lmaldo@inta.gov.ar ; aalvarez@inta.gov.ar ; anvander@inta.gov.ar

[cxxx] Abstract

El propóleos es un producto resinoso extraído por las abejas a partir de cortezas de ciertos árboles y arbustos silvestres, que los utilizan para proteger la colmena de daños externos, y también como material de construcción, reparación y aislamiento. Estos daños se deben a la entrada de organismos tanto micro como macroscópicos (desde bacterias, hongos, etc.; hasta ratas, insectos), inclusive corrientes de aire, humedad; y la protección se produce gracias a la acción antibiótica del propóleos. Debido a esta acción y por ser una sustancia natural e inocua es ampliamente utilizada tanto internamente contra infecciones de vías respiratorias (anginas, faringitis, bronquitis), digestivas (gingivitis); como externamente en lesiones de piel (heridas, quemaduras, úlceras, abscesos).

Posee una composición química compleja y la acción farmacológica la ejerce a través de sustancias tales como: flavonoides, fenoles, oligoelementos, ácidos muy poderosos, desde el punto de vista reparador, sobre el organismo humano o animal.

El objetivo de este estudio fue la investigación de la actividad antimicrobiana de propóleos (extractos etanólicos) de distintas procedencias de la Argentina, enfrentados con cepas ATCC de Staphylococcus aureus (penicilina G resistente).

Se analizaron 35 muestras de extractos etanólicos de propóleos. La actividad antibacteriana se observó por la presencia de halos de inhibición por el método de difusión en placa en pocillos. El inóculo se preparó a partir de un cultivo puro y fresco de Staphylococcus aureus ATCC 25923. Se arrastró la biomasa en condiciones asépticas con solución fisiológica estéril hasta alcanzar la turbidez del tubo 0,5 de la Escala de Mc Farland. En cada placa se utilizó un pocillo con etanol al 70% para control negativo. Se cargó los pocillos con las muestras al 10%, se llevó a refrigeración durante 2 horas y luego fue incubado aeróbicamente a 35 – 37 °C durante 18 – 24 hs.

Luego de la incubación se realizaron las lecturas tomando como positivo los orificios en cuyo entorno se observaron halos de inhibición transparentes. Los extractos que presentaron halos de inhibición fueron aceptados. La medición de halos se realizó con un calibrador (tomando el promedio del diámetro de inhibición en distintas direcciones para minimizar el error).

Los resultados de la actividad antibacteriana de extractos etanólicos de propóleos fueron expresados en milímetros, considerando valores promedios por provincia:

Provincia	Buenos Aires	Mendoza	Catamarca	Tucumán	Chaco	Sgo. del Estero	La Rioja
Promedio (mm)	14,20	14,50	17,16	16,74	12,97	12,25	13,50

Por lo expuesto se deduce que las muestras de las provincias del Noroeste tienen mayor poder antibacteriano frente a Staphylococcus aureus, que el resto de las regiones del país.

[cxxxi] Tsarev, N. I.; Petrik, E. V.; Aleksandrova, V. I. (1985) – Use of propolis in the treatment of local suppurative infection,
in Vestn Khir, May, 134 (5), pp.119-22 (abstract).

Experience with the treatment of 460 patients with panaritium, abscesses, phlegmons, infectious wounds have shown that propolis is an expedient remedy (in additional to the routine treatment). They have shown the stimulating, antiinflammatory and anti-microbial action of propolis.

[cxxxii] VERSUCHE ZUR BEHANDLUNG EINIGER PARADONTOPATHIEN

MIT APITHERAPIEPRODUKTEN

N. VARACHIU
N. LUCA
Filofteia POPESCU
Cristina MATEESCU
Gh. PIRVU

Experimentell und klinisch wird die Wirkung eines neuen Apitherapieprodukts untersucht, u. zwar mit Bienengift und Pollen vermischte Propolis. Dieses produkt wurde bei der Behandlung von Paradontopathien verwendet. Die Untersuchungen erfolgten mit Hunden, vor allem der Beagle-Rasse.

Das Referat bringt die erhaltenen Ergebnisse.
S. 545

[cxxxiii] Vlietinck,A.J., De Bruyne,T., Apers,S., & Pieters,L.A. (1998) – Plant-derived leading compounds for chemotherapy of human immunodeficiency virus (HIV) infection,
in Planta Med 64(2), 97-109 (***).

Many compounds of plant origin have been identified that inhibit different stages in the

replication cycle of human immunodeficiency virus (HIV): 1) virus adsorption: chromone alkaloids (schumannificine), isoquinoline alkaloids (michellamines), sulphated polysaccharides and polyphenolics, flavonoids, coumarins (glycocoumarin, licopyranocoumarin) phenolics (caffeic acid derivatives, galloyl acid derivatives, catechinic acid derivatives), tannins and triterpenes (glycyrrhizin and analogues, soyasaponin and analogues); 2) virus-cell fusion: lectins (mannose- and N-acetylglucosamine-specific) and triterpenes (betulinic acid and analogues); 3) reverse transcription; alkaloids (benzophenanthridines, protoberberines, isoquinolines, quinolines), coumarins (calanolides and analogues), flavonoids, phloroglucinols, lactones (protolichesterinic acid), tannins, iridoids (fulvoplumierin) and triterpenes; 4) integration:

coumarins (3- substituted-4-hydroxycoumarins), depsidones, O-caffeoyl derivatives, lignans (arctigenin and analogues) and phenolics (curcumin); 5) translation: single chain ribosome inactivating proteins (SCRIP’s); 6) proteolytic cleavage (protease inhibition): saponins (ursolic and maslinic acids), xanthones (mangostin and analogues) and coumarins; 7) glycosylation: alkaloids including indolizidines (castanospermine and analogues), piperidines (1-deoxynojirimicin and analogues) and pyrrolizidines (australine and analogues); 8) assembly/release: naphthodianthrones (hypericin and pseudohypericin), photosensitisers

(terthiophenes and furoisocoumarins) and phospholipids. The target of action of several anti-HIV substances including alkaloids (O-demethyl-buchenavianine, papaverine), polysaccharides (acemannan), lignans (intheriotherins, schisantherin), phenolics (gossypol, lignins, catechol

dimers such as peltatols, naphthoquinones such as conocurvone) and saponins (celasdin B, Gleditsia and Gymnocladus saponins), has not been elucidated or does not fit in the proposed scheme. Only a very few of these plant-derived anti-HIV products have been used in a limited number of patients suffering from AIDS viz. glycyrrhizin, papaverine, trichosanthin,

castanospermine, N-butyl-1-deoxynojirimicin and acemannan.

[cxxxiv] Volpert, R.; Elstner, E. F. (1993) – Biochemical activities of propolis extracts. I. Standardization and antioxidative properties of ethanolic and aqueous derivatives,
in Zeitschrift fur Naturforschung. Section C (Journal of Biosciences), 48(11-12), pp.851-57 (***).
Abstract
Ethanolic extracts of Propolis are used as antiinflammatory and wound healing drugs since ancient times. In order to facilitate a comparison of different extracts, the standardization on the basis of quantitative determination of prominent components of these extracts has been substituted for simple biochemical “activity” tests. One of these activity tests bases on the inhibition of peroxidase-catalyzed oxidation of indole acetic acid indicating the presence of a defined mixture of monophenolic and diphenolic compounds. Other tests (diaphorase-catalyzed reductions and xanthine oxidase-catalyzed oxidations) demonstrate significant radical scavenging properties. Water-soluble extracts of propolis exhibit higher antioxidative and inhibitory activities as compared to the ethanolic extract.

[cxxxv] Volpert, R.; Elstner, E. F. (1993) – Biochemical activities of propolis extracts. II. Photodynamic activities,
in Zeitschrift fur Naturforschung. Section C. ( Journal of Biosciences), Nov- Dec. 48(11-12), pp.858-62 (***).

Abstract
Ethanolic and aqueous extracts of the “bee glue” Propolis exhibit antioxidative properties and are used as antiinflammatory drugs in folk medicine. In order to standardize the principle activities of prominent components of these extracts, simple biochemical tests have been introduced in the preceding paper. These activity tests prove the high antioxidative and inhibitory capacities of aqueous and ethanolic extracts of propolis in vitro. In the present communication we report on experiments documenting photodynamic quenching properties of these extracts. Using riboflavin, rose bengal or hematoporphyrin as photoactivators and ketomethylthiobutyric acid or crocin as indicators, the protective functions of propolis preparations can be demonstrated. The results indicate that the aqueous extracts are more active than the corresponding ethanolic preparation.

[cxxxvi] Volpert, R.; Elstner, E. F. (1996) (Germany) – Interactions of different extracts of propolis with leukocytes and leukocytic enzymes,
in Arzneimittelforschung, Jan;46(1), pp.47-51.

Authors address: Lehrstuhl fur Phytopathologie, Technische Universitat Munchen, Freising-Weihenstephan, Germany.

Extracts of the “bee glue” propolis exhibit well-known antioxidative and anti-inflammatory properties. However, the biochemical mechanisms of propolis effects in wound healing and inflammatory processes are not yet fully understood. Therefore the effects of different ethanolic and aqueous extracts on leukocytes and some of their most important enzymes namely myeloperoxidase, NADPH oxidase and lipoxygenase were investigated. Only high concentrations of propolis extracts inhibited these enzymatic activities but especially the water-soluble derivatives showed stimulatory effect on the activity of commercially available human myeloperoxidase. Leukocytic myeloperoxidase and NADPH oxidase activities were clearly inhibited by propolis extracts probably indirectly due to their excellent radical scavenging properties.
PMID: 8821517, UI: 96418732.

[cxxxvii] Völker Wilhelm Addresse: Gündinger Strasse 1 A, 81249 München, Germany.

[cxxxviii] Yamada, J.; Tomita, Y. (1996) – Antimutagenic activity of caffeic acid and related compounds,
in Biosci. Biotechnol. Biochem., 60(2), pp.328-29 (abstract).

Effects of caffeic acid and chlorogenic acid on mutagenicity were studied using the Salmonella typhimurium system. These compounds had inhibitory effects on the mutagenicity of Trp-P-1 and Glu-P-2. Caffeic acid completely eliminated the mutagenicity induced by activated Glu-P- 2. Some compounds analogous to caffeic acid, such as cinnamic acid, coumaric acid, and ferulic acid, also significantly decreased the mutagenicity of Glu-P-2.

[cxxxix] WIRKUNG UND VERWENDUNG VON PROPOLIS

IN VETERINÄR-ARZNEIMITTELN

YANG RUIYU
PENG HELU
HE SHAOYU
(China)

Über die Verwendung der Propolis in Veterinärarzneimitteln wurde nicht berichtet. Im Rahmen unserer Untersuchung wurden die Wirkungen und die Anwendungen der Propolis in der Veterinärmedizin studiert. Die Infektionsmikroorganismen der Haustiere, die für den menschlichen Organismus eine Gefahr darstellen, stammen von 17 Spezies. Diese Mikroorganismen sind : Staphylococcus aureus, Streptococcus equi, Erysipelothrix rhusiopathiae, Pasteurella suiseptica, Pas -teurella boviseptica, Salmonella abortus-equi, Satmonella cholerae suis, Salmonella pullorum, Salmonella gallinarum, Bacillus coli, Listerella monocytogenes, Salmonella paratyphi A., Salmonella paratyphi B., Salmonella typhi, Pseudomonas aeruginosa, Streptococcus B und Sh. flexner.

S. 559

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27 September 2020

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[xlvi] Abstract

Muestras

Tiempo

Los resultados de la actividad antibacteriana de extractos etanólicos de propóleos fueron expresados en milímetros, considerando valores promedios por provincia:

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