Evaluation of the gastroprotective activity of cordatin, a diterpene isolated from Aparisthmium cordatum (Euphorbiaceae)

Aparisthmium cordatum (Juss.) BAIL. (Euphorbiaceae) is a medium sized tree native to the North Brazilian coastal region, which is known in the State o f Para as "ariquena queimosa." To our knowledge it has no popular use. Phyt ochemical studies of the benzene extract of the bark of A. cordatum yielded a furan diterpene with a clerodane skeleton, called cardatin. Recently, we reported the antiulcerogenic activity of trans-dehydrocrotonin (DHC), anot her furan diterpene isolated from Croton cajucara bark, in different ulcero genic models in mice and rats. The aim of the present study was to assess t he possible antiulcerogenic activity of cordatin, another compound of the c lerodane diterpene group present in A. cordatum bark. When previously admin istered (p.o.) at the dose of 100 mg/kg, cordatin significantly reduced (p< 0.01) gastric injury induced by the indomethacin/bethanechol (78%), ethanol (76%), and hypothermic restraint-stress models (66%) and by pylorus ligatu re (50%) in mice and rats. In the HCl/ethanol-induced gastric ulcer model i n mice, at oral doses of 100 and 250 mg/kg, cordatin from A. cordatum signi ficantly 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 intraduodena lly to mice, significant modifications were found, such as a decrease in ga stric 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 anti-ulcer effect when assessed in these induced ulcer model s. Although the mechanism underlying this antiulcerogenic effect remains un known, it seems to be related to an anti-secretory property but the involve ment of mucosal defensive mechanisms are not to be ignored. The good yield of cordatin obtained from A. cordatum, as well as its antiulcerogenic activ ity, suggest that this compound should be submitted to pharmacological rese arch as a potential new antiulcerogenic drug.