Antiulcerogenic mechanisms of dehydrocrotonin, a diterpene lactone obtained from Croton cajucara

The bark of Croton cajucara Benth. is used in Brazilian folk medicine as an infusion to treat gastrointestinal disorders. The aim of the present study was to assess the mechanisms involved in the antiulcerogenic activity of d ehydrocrotonin (DHC), a diterpene isolated from C. cajucara bark. We studie d the effects of DHC on pylorus ligature (Shay) in mice treated with the dr ug (100 mg/kg) by the intraduodenal route. DHC did not induce any alteratio n in gastric volume in Shay mice but modified the pH and total acid concent ration of gastric juice. Incubation of gastric juice with DHC did not reduc e gastric acidity compared to control. We also investigated the effects of DHC on the response to histamine of Fight atria isolated from guinea pigs a nd on the response to carbachol of stomach fundus strips from rats. The con centration-response curves for the chronotropic effect of histamine in guin ea pig right atria were shifted to the right, with a significant decrease i n the maximum response, in the presence of DHC. Similar results were obtain ed with DHC (30 mu M) for the concentration-response curves to carbachol in the isolated rat stomach. The ability of DHC to increase PGE(2) release fr om rat stomach mucous cells was also studied. We observed that DHC induced a significant increase in PGE(2) production (60% compared to control). In a ddition, the effects of DHC on the healing of acetic acid-induced gastric u lcer in rats were evaluated 14 days after acid injection. Oral administrati on of DHC (100 mg/kg per day) for 14 consecutive days had no effect on gast ric ulcer healing in rats. Thus, the protective effect of DHC on induced ga stric lesions could be, due to synergistic effects, e.g., an increase in PG E(2) release and non-competitive antagonism of H-2-receptors and of muscari nic receptors. Whereas the former result represents an increase in the prot ective factors, the latter one shows a decrease in the aggressive factors a gainst the gastric mucosa.