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 dehydrocrotonin (DHC), a diterpene isolated from C. cajucara bark. We studied the effects of DHC on pylorus ligature (Shay) in mice treated with the drug (100 mg/kg) by the intraduodenal route. DHC did not induce any alteration in gastric volume in Shay mice but modified the pH and total acid concentration of gastric juice. Incubation of gastric juice with DHC did not reduce gastric acidity compared to control. We also investigated the effects of DHC on the response to histamine of Fight atria isolated from guinea pigs and on the response to carbachol of stomach fundus strips from rats. The concentration-response curves for the chronotropic effect of histamine in guinea pig right atria were shifted to the right, with a significant decrease in the maximum response, in the presence of DHC. Similar results were obtained 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 from rat stomach mucous cells was also studied. We observed that DHC induced a significant increase in PGE(2) production (60% compared to control). In addition, the effects of DHC on the healing of acetic acid-induced gastric ulcer in rats were evaluated 14 days after acid injection. Oral administration of DHC (100 mg/kg per day) for 14 consecutive days had no effect on gastric ulcer healing in rats. Thus, the protective effect of DHC on induced gastric lesions could be, due to synergistic effects, e.g., an increase in PGE(2) release and non-competitive antagonism of H-2-receptors and of muscarinic receptors. Whereas the former result represents an increase in the protective factors, the latter one shows a decrease in the aggressive factors against the gastric mucosa.