Abstract
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 right 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 µM) for the concentration-response curves to carbachol in the isolated
rat stomach. The ability of DHC to increase PGE2 release from rat stomach mucous cells was also studied. We observed that DHC induced
a significant increase in PGE2 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 PGE2 release and non-competitive antagonism of H2-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.
Key words
Croton cajucara
- Euphorbiaceae - dehydrocrotonin - cytoprotective effect - antiulcerogenic activity
- anti-secretory effect