Antiulcerogenic Effect of Brazilian Propolis Formulation in Mice

DOI: 10.4236/pp.2015.612060   PDF   HTML   XML   4,446 Downloads   5,126 Views   Citations


Propolis is a natural resin used around the world to treatment of several diseases. We evaluated the effect of Brazilian propolis (P1) in guinea pig isolated trachea in vitro contracted with hista-mine, in paw oedema induced by histamine in mice and anti-ulcerogenic effect of propolis formulation in mice. We used a P1 extract from South of Brazil to produce a formulation containing sodium bicarbonate and propolis dry extract (2%). In the guinea pig trachea Brazilian propolis extract (10 μg/mL) produced a non-significant inhibition in the cumulative response curve for histamine. However, the dose of 100 μg/mL shown had a significant inhibitory effect on the contraction induced by histamine (51% ± 5%). In the mouse paw oedema induced by intraplantar injection of histamine (50 μg/paw), the results showed that the treatment of the mice with P1 (10 or 100 mg/Kg (p.o) or 1 or 10 mg/Kg (i.p)), 0.5 h beforehand, significantly inhibited the paw oedema with maximal inhibition (MI) of 25% or 42% by p.o. route or 22% or 37% by i.p. route, respectively. Finally we have pre-treated mice with P1 formulation (20 mg/Kg or 40 mg/Kg, p.o, one time) or vehicle (powder) in animals submitted to diclofenac-induced ulcer, after 8 h P1 formulation inhibited of 43% or 83% of ulcers scores, respectively. Results showed that P1 formulation inhibited the ulcerogenic effect induced by diclofenac. Results suggested also, at least in part, the antiulcerogenic effect of formulation containing standardized extract of propolis can be due to the antagonistic action on the histaminergic system.

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Paulino, N. , Coutinho, L. , Coutinho, J. , Vilela, G. , Silva Leandro, V. and Paulino, A. (2015) Antiulcerogenic Effect of Brazilian Propolis Formulation in Mice. Pharmacology & Pharmacy, 6, 580-588. doi: 10.4236/pp.2015.612060.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Debiaggi, M., Tateo, F., Pagani, L., Luini, M. and Romero, E. (1990) Effects of Propolis Flavonoids on Virus Infectivity and Replication. Microbiologica, 13, 207-213.
[2] Dimov, V., Ivanovska, N., Bankova, V. and Popov, S. (1992) Immunomodulatory Action of Propolis. IV. Prophylactic Activity against Gram-Negative Infections and Adjuvant Effect of the Water-Solubble Derivative. Vaccine, 10, 817-823.
[3] Crisan, I., Rojanschi, D., Petica, M., et al. (1996) Testing of the in Vivo Therapeutic Efficacy on the Cutaneous Herpes Simplex Infections of the Autochthonous Product 5% Acyclovir Ointment Rom. Journal of Virology, 47, 13-24.
[4] Scheller, S., Krol, W., Swiacik, J., Owczarek, S., Gabrys, J. and Shani, J. (1989) Antitumoral Property of Ethanolic Extract of Propolis in Mice-Bearing Ehrlich Carcinoma, as Compared to Bleomycin. Zeitschrift für Naturforschung, 44C, 1063-1065.
[5] De Campos, R.O.P., Paulino, N., Da Silva, C.H.M., Scremin, A. and Calixto, J.B. (1998) Antihiperalgesic Effect of Na Ethanolic Extract of Propolis on Mice and Rats. Journal of Pharmacy and Pharmacology, 50, 1187-1193.
[6] Ledón, N., Casacó, A., González, R., Merino, N., González, A. and Tólon, Z. (1997) Antipsoriatic, Anti-Inflammentory, and Analgesic Effects of an Extract of Repropolis. Acta Pharmacol Sinica, 18, 274-278.
[7] Park, E., Kim, S. and Park, S. (1996) Anti-Inflammatory Activity of Propolis. Archives of Pharmacal Research, 5, 337-339.
[8] Paulino, N., Teixeira, C., Martins, R, Scremin, F.M., Scremin, A., Dirsch, V.M., Vollmar, A.M., Abreu, S.R.L., De Castro, S.L. and Marcucci, M.C. (2006) Evaluation of the Analgesic and Anti-Inflammatory Effects of a Brazilian Green Propolis. Planta Medica, 72, 899-906.
[9] Paulino, N., Coutinho, J.R., Coutinho, L.M. and Paulino, A.S. (2014) Clinical Evaluation of the Anti-Inflammatory Effect of Baccharis dracunculifolia Propolis Gel on Cervicitis. Revista Ciência e Estudos Acadêmicos de Medicina, 2, 31-46.
[10] Pascual, C., Gonzalez, R. and Torricella, R.G. (1994) Scavenging Action of Propolis Extract against Oxygen Radicals. Journal of Ethnopharmacology, 41, 9-13.
[11] Basnet, P., Matsuno, T. and Neidlein, R. (1997) Potent Free Radical Scavenging Activity of Propol Isolated from Brazilian Propolis. Zeitschrift für Naturforschung C, 52, 828-833.
[12] Aga, H., Shibuya, T., Sugimoto, T., Kurimoto, M. and Nakajima, S. (1994) Isolation and Identification of Antimicrobial Compounds in Brazilian Propolis. Bioscience Biotechnology and Biochemistry, 58, 945-946.
[13] Martos, I., Cossentini, M., Ferreres, F. and Tomás-Barberán, F.A. (1997) Flavonoid Composition of Tunisian Honeys and Propolis. Journal of Agricultural and Food Chemistry, 45, 2824-2828.
[14] Banskota, A.H., Tezuka, Y., Prasain, J.K., Matsushige, K., Saiki, I. and Kadota, S. (1998) Chemical Constituents of Brazilian Propolis and Their Cytotoxic Activities. Journal of Natural Products, 61, 896-900.
[15] Bankova, V. (2005) Chemical Diversity of Propolis and the Problem of Standardization. Journal of Ethnopharmacology, 100, 114-117.
[16] Marcucci, M.C., Ferreres, F., Garcia-Viguera, C., Bankova, V.S., De Castro, S.L., Dantas, A.P., Valente, P.H. and Paulino, N. (2001) Phenolic Compounds from Brazilian Propolis with Pharmacological Activities. Journal of Ethnopharmacology, 74, 105-112.
[17] Paulino, N., Scremin, F.M., Raichaski, L.B., Marcucci, M.C., Scremin, A. and Calixto, J.B. (2002) Mechanisms Involved in the Relaxant Action of the Ethanolic Extract of Propolis in the Guinea Pig Trachea in Vitro. Journal of Pharmacy and Pharmacology, 54, 845-852.
[18] Van Rosum, J.M. (1963) Technique for the Making of Dose-Response Curves in Isolated Organs and the Evaluation of Drug Parameters. Archives Internationales de Pharmacodynamie et de Therapie, 143, 299-330.
[19] Paulino, N., Pizollatti, M.G., Yunes, R.A., Filho, V.C., Creczynski-Pasa, T.B. and Calixto, J.B. (1999) The Mechanisms Underlying the Relaxant Effect of Methyl and Ethyl Gallates in the Guinea Pig Trachea in Vitro: Contribution of Potassium Channels. Naunyn-Schmiedeberg’s Archives of Pharmacology, 360, 331-336.
[20] Paulino, N., Scremin, F.M., Raichaski, L.B., Marcucci, M.C., Scremin, A. and Calixto, J.B. (2002) Mechanisms Involved in the Relaxant Action of the Ethanolic Extract of Propolis in the Guinea Pig Trachea in Vitro. Journal of Pharmacy and Pharmacology, 54, 845-852.
[21] Zimmermann, M. (1983) Ethical Guidelines for Investigation of Pain in Conscious Animals. Pain, 16, 109-110.
[22] Calixto, J.B., Zanini, J.C., Cruz, A.B., Yunes, R.A. and Medeiros, Y.S. (1991) Extract and Compounds Obtained from Mandevilla velutina Inhibit Arachidonic Acid-Induced Ear or Edema in Mice, but Not Rat Stomach Contraction. Prostaglandins, 41, 515-526.
[23] Tanaka, S. and Ichikawa, A. (2006) Recent Advances in Molecular Pharmacology of the Histamine Systems: Immune Regulatory Roles of Histamine Produced by Leukocytes. Journal of Pharmacological Sciences, 101, 19-23.
[24] Oppenheimer, J. and Nelson, H.S. (2006) Skin Testing: A Survey of Allergists. Annals of Allergy, Asthma & Immunology, 96, 19-23.
[25] Kyllonen, H., Malmberg, P., Remitz, A., Rytila, P., Metso, T., Helenius, I., Haahtela, T. and Reitamo, S. (2006) Respiratory Symptoms, Bronchial Hyper-Responsiveness, and Eosinophilic Airway Inflammation in Patients with Moderate-to-Severe Atopic Dermatitis. Clinical & Experimental Allergy, 36, 192-197.
[26] Schneeweiss, S., Maclure, M., Dormuth, C.R., Glynn, R.J., Canning, C. and Avorn, J. (2006) A Therapeutic Substitution Policy for Proton Pump Inhibitors: Clinical and Economic Consequences. Clinical Pharmacology & Therapeutics, 79, 379-388.
[27] Schubert, M.L. (2005) Gastric Secretion. Current Opinion in Gastroenterology, 21, 636-643.
[28] Escribano, L., Akin, C., Castells, M. and Schwartz, L.B. (2006) Current Options in the Treatment of Mast Cell Mediator-Related Symptoms in Mastocytosi. Inflammation & Allergy-Drug Targets, 5, 61-77.
[29] Barnes, P.J. (1991) Histamine Receptors in the Lung. Agents and Actions Supplements, 33, 103-122.
[30] Togias, A. (2003) H1-Receptors: Localization and Role in Airway Physiology and in Immune Functions. Journal of Allergy and Clinical Immunology, 112, S60-S68.
[31] MacGlashan Jr., D. (2003) Histamine: A Mediator of Inflammation. Journal of Allergy and Clinical Immunology, 112, S53-S59.
[32] Sy, L.B., Wu, Y.L., Chiang, B.L., Wang, Y.H. and Wu, W.M. (2006) Propolis Extracts Exhibit an Immunoregulatory Activity in an OVA-Sensitized Airway Inflammatory Animal Model. International Immunopharmacology, 6, 1053-1060.
[33] Paulino, N., Dantas, A.P., Bankova, V.S., Longhi, D.T., Scremin, A., Castro, S.L. and Calixto, J.B. (2003) Bulgarian Propolis Induces Analgesic and Anti-Inflammatory Effects in Mice and Inhibits in Vitro Contraction of Airway Smooth Muscle. Journal of Pharmaceutical Sciences, 93, 307-313.
[34] Paulino, N., Abreu, S.R., Uto, Y., Koyama, D., Nagasawa, H., Hori, H., Dirsch, V.M., Vollmar, A.M., Scremin, A. and Bretz, W.A. (2008) Anti-Inflammatory Effects of a Bioavailable Compound, Artepillin C, in Brazilian Propolis. European Journal of Pharmacology, 587, 296-301.
[35] Lima, L.D., Andrade, S.P., Campos, P.P., Barcelos, L.S., Soriani, F.M., Moura, S.A. and Ferreira, M.A. (2014) Brazilian Green Propolis Modulates Inflammation, Angiogenesis and Fibrogenesis in Intraperitoneal Implant in Mice. BMC Complementary and Alternative Medicine, 14, 177.
[36] Mirzoeva, O.K. and Calder, P.C. (1996) The Effect of Propolis and Its Components on Eicosanoid Production during the Inflammatory Response. Prostaglandins, Leukotrienes and Essential Fatty Acids, 55, 441-449.
[37] Ansorge, S., Reinhold, D. and Lendeckel, U. (2003) Propolis and Some of Its Constituents Down-Regulate DNA Synthesis and Inflammatory Cytokine Production but Induce TGF-Beta1 Production of Human Immune Cells. Zeitschrift für Naturforschung, 58, 580-589.
[38] Hu, F., Hepburn, H.R., Li, Y., Chen, M., Radloff, S.E. and Daya, S. (2005) Effects of Ethanol and Water Extracts of Propolis (Bee Glue) on Acute Inflammatory Animal Models. Journal of Ethnopharmacology, 100, 276-283.
[39] Lima Cavendish, R., de Souza Santos, J., Belo Neto, R., Oliveira Paixão, A., Valéria Oliveira, J., Divino de Araujo, E., Berretta, E., Silva, A.A., Maria Thomazzi, S., Cordeiro Cardoso, J. and Zanardo Gomes, M. (2015) Antinociceptive and Anti-Inflammatory Effects of Brazilian Red Propolis Extract and Formononetin in Rodents. Journal of Ethnopharmacology, 173, 127-133.
[40] de Moura, S.A., Ferreira, M.A., Andrade, S.P., Reis, M.L., Noviello Mde, L. and Cara, D.C. (2011) Brazilian Green Propolis Inhibits Inflammatory Angiogenesis in a Murine Sponge Model. Evidence-Based Complementary and Alternative Medicine, 2011, Article ID: 182703.
[41] Katz, P.O. and Tutuian, R. (2001) Histamine Receptor Antagonists, Proton Pump Inhibitors and Their Combination in the Treatment of Gastro-Oesophageal Reflux Disease. Best Practice & Research Clinical Gastroenterology, 15, 371-384.
[42] Sturkenboom, M.C., Burke, T.A., Tangelder, M.J., Dieleman, J.P., Walton, S. and Goldstein, J.L. (2003) Adherence to Proton Pump Inhibitors or H2-Receptor Antagonists during the Use of Non-Steroidal Anti-Inflammatory Drugs. Alimentary Pharmacology & Therapeutics, 18, 1137-1147.
[43] Mossner, J. and Caca, K. (2005) Developments in the Inhibition of Gastric Acid Secretion. European Journal of Clinical Investigation, 35, 469-475.
[44] McCarthy, D.M. (2002) Ulcers, Helicobacter pylori Infection, Platelets and Gastrointestinal Complications of Non-Steroidal Anti-Inflammatory Drugs: What Are the Connections? European Journal of Surgery—Supplements, 587, 89-99.
[45] Graham, D.Y. (2002) NSAIDs, Helicobacter pylori, and Pandora’s Box. New England Journal of Medicine, 347, 2162-2164.
[46] Massignani, J.J., Lemos, M., Maistro, E.L., Schaphauser, H.P., Jorge, R.F., Sousa, J.P., Bastos, J.K. and de Andrade, S.F. (2009) Antiulcerogenic Activity of the Essential Oil of Baccharis dracunculifolia on Different Experimental Models in Rats. Phytotherapy Research, 23, 1355-1360.
[47] Banskota, A.H., Tezuka, Y., Adnyana, I.K., Ishii, E., Midorikawa, K., Matsushige, K. and Kadota, S. (2001) Hepatoprotective and Anti-Helicobacter pylori Activities of Constituents from Brazilian Propolis. Phytomedicine, 8, 16-23.
[48] Nostro, A., Cellini, L., Di Bartolomeo, S., Di Campli, E., Grande, R., Cannatelli, M.A., Marzio, L. and Alonzo, V. (2005) Antibacterial Effect of Plant Extracts against Helicobacter pylori. Phytotherapy Research, 19, 198-202.
[49] Nostro, A., Cellini, L., Di Bartolomeo, S., Cannatelli, M.A., Di Campli, E., Procopio, F., Grande, R., Marzio, L. and Alonzo, V. (2006) Effects of Combining Extracts (From Propolis or Zingiber officinale) with Clarithromycin on Helicobacter pylori. Phytotherapy Research, 20, 187-190.
[50] Lamarque, D. (2004) Pathogenesis of Gastroduodenal Lesions Induced by Non-Steroidal Anti-Inflammatory Drugs. Gastroentérologie Clinique et Biologique, 3, C18-C26.
[51] Nakanishi, I., Uto, Y., Ohkubo, K., Miyazaki, K., Yakumaru, H., Urano, S., Okuda, H., Ueda, J., Ozawa, T., Fukuhara, K., Fukuzumi, S., Nagasawa, H., Hori, H. and Ikota, N. (2003) Efficient Radical Scavenging Ability of Artepillin C, a Major Component of Brazilian Propolis, and the Mechanism. Organic & Biomolecular Chemistry, 1, 1452-1454.
[52] Shimizu, K., Ashida, H., Matsuura, Y. and Kanazawa, K. (2004) Antioxidative Bioavailability of Artepillin C in Brazilian Propolis. Archives of Biochemistry and Biophysics, 424, 181-188.
[53] Liu, C.F., Lin, C.C., Lin, M.H., Lin, Y.S. and Lin, S.C. (2002) Cytoprotection by Propolis Ethanol Extract of Acute Absolute Ethanol-Induced Gastric Mucosal Lesions. American Journal of Chinese Medicine, 30, 245-254.

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