Artepillin C, drupanin, aromadendrin-4'-O-methyl-ether and kaempferide from Brazilian green propolis promote gastroprotective action by diversified mode of action.

Ethopharmacological relevance: The propolis is extensively used in folk medicine in natura or to prepare pharmaceutical formulations since ancient time to improve health or prevent diseases, among them gastrointestinal disorders. Aiming to contribute in the scientific validation about the popular use of Brazilian Green propolis (BGP) against gastritis and gastric ulcer, this work evaluated the antiulcer potential of isolated compounds from BGP, three prenylated p-coumaric acid derivatives and two flavonoids, respectively named: 3,5 diprenyl-4-hydroxycinnamic acid (artepillin C) (1), 3-prenyl-4-dihydroxycinnamoiloxy cinnamic acid (baccharin) (2), 3-prenyl-4-hydroxycinnamic acid (drupanin) (3), aromadendrin-4'-O-methyl-ether (4) and kaempferide (5). Material and methods: The compounds were characterized by nuclear magnetic resonance and mass spectrometry. Their gastroprotective effects were evaluated against ethanol/HCl- and indomethacin-induced ulcer in mice. Further, histological, histochemical, oxidative and inflammatory parameters were analyzed at ulcerated tissue. Acid antisecretory activities also were also assessed. Results: Compound 2 did not reduce the ethanol/HCl- induced ulcer at 30 mg/kg (p.o), whereas the minimum oral gastroprotective doses of 1, 3, 4 and 5 were 0.3, 0.3, 3 and 3 mg/kg, respectively. Besides, these compounds prevented ethanol/HO-induced ulcer by intraperitoneal route, as well as indomethacin-induced ulcer by oral route. The gastroprotection was accompanied by normalization of superoxide dismutase, catalase and glutathione-S-transferase activities and reduction in myeloperoxidase activity. Moreover, the compounds 4 and 5 increased the gastric mucin content and 1 reduced TNF amount. Furthermore, 1, 3, 4 and 5 decreased volume, pH, total acidity and pepsin activity of the gastric juice from rats. Conclusions: Together, our findings showed a diversified mode of action elicited by 1, 3, 4 and 5 on the gastroprotection and contribute to explain the anti-ulcer activity reported for BGP.