Biol. Pharm. Bull., 23(12),1465-1469, December 2000

Evaluation of the Gastroprotective Activity of Cordatin, a Diterpene Isolated from Aparisthmium cordatum (Euphorbiaceae)

Clelia Akiko HIRUMA-LIMA,^a Juliano de Souza GRACIOSO,^b Walber TOMA,^b Ana Claudia Bensuaski de PAULA,^b Ana Beatriz Albino de ALMEIDA,^c Davi do Socorro Barros BRASIL,^d Adolfo Henrique MULLER,^d and Alba Regina Monteiro Souza BRITO^{*, b}

Instituto de Biologia e Saúde Pública, Campus Porto Nacional, Universidade do Tocantins, Porto Nacional,^a Tocantins, Brazil, Departamento de Fisiologia, Instituto de Biologia, Universidade Estadual de Campinas,^b Campinas, São Paulo, Brazil, Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas,^c Campinas, São Paulo, Brazil, and Departamento de Química, Centro de Ciéncias Exatas e da Natureza, Universidade Federal do Pará,^d Belém, Pará, Brazil.

Aparisthmium cordatum (JUSS.) BAIL. (Euphorbiaceae) is a medium sized tree native to the North Brazilian coastal region, which is known in the State of Pará as "ariquena queimosa." To our knowledge it has no popular use. Phytochemical studies of the benzene extract of the bark of A. cordatum yielded a furan diterpene with a clerodane skeleton, called cordatin. Recently, we reported the antiulcerogenic activity of trans-dehydrocrotonin (DHC), another furan diterpene isolated from Croton cajucara bark, in different ulcerogenic models in mice and rats. The aim of the present study was to assess the possible antiulcerogenic activity of cordatin, another compound of the clerodane diterpene group present in A. cordatum bark. When previously administered (p.o.) at the dose of 100 mg/kg, cordatin significantly reduced (p<0.01) gastric injury induced by the indomethacin/bethane-chol (78%), ethanol (76%), and hypothermic restraint-stress models (66%) and by pylorus ligature (50%) in mice and rats. In the HCl/ethanol-induced gastric ulcer model in mice, at oral doses of 100 and 250 mg/kg, cordatin from A. cordatum significantly reduced (p<0.001) the formation of gastric lesions by 70% and 77%, respectively, when compared to the control. In the pylorus-ligature model, cordatin (p.o.) only decreased the volume of gastric juice compared to the control (p<0.001). When cordatin (100 mg/kg) was administered intraduo-denally to mice, significant modifications were found, such as a decrease in gastric acidity compared to the control (p<0.05). In the animals pre-treated with cordatin, free mucus production was not altered when compared with the control group. The results suggest that cordatin from A. cordatum presents a significant antiulcer effect when assessed in these induced ulcer models. Although the mechanism underlying this antiulcerogenic effect remains unknown, it seems to be related to an anti-secretory property but the involvement of mucosal defensive mechanisms are not to be ignored. The good yield of cordatin obtained from A. cordatum, as well as its antiul-cerogenic activity, suggest that this compound should be submitted to pharmacological research as a potential new antiulcerogenic drug.

Key words gastroprotective activity; cordatin; Aparisthmium cordatum; Euphorbiaceae