Abstract:
The present study was designed to evaluate the anti-ulcerogenic properties of an alkaloid chromane, rohitukine from Dysoxylum binecteriferum. Anti-ulcer potential of rohitukine was assessed in cold restrained, pyloric ligated and ethanol induced ulcers in rats. Also, rohitukine was tested in vitro for H+ K+-ATPase inhibitory activity in gastric microsomes. Moreover, we studied the role of rohitukine on the cytosolic concentration of Ca2+ in parietal cell enriched cell suspension in order to ascertain its mechanism of action. Cytoprotective activity was evaluated through PGE2 level. Rohitukine significantly attenuated the ulcers in CRU model in a dose-related manner. Moreover, it significantly lowered the free acidity and pepsin activity in pyloric ligated rats while improved the depleted level of mucin. Also, rohitukine significantly reversed the cold restrained-induced increase in gastrin level. Our in vitro study revealed that rohitukine moderately inhibited the microsomal H+ K+-ATPase activity with respect to positive control omeprazole. Furthermore, rohitukine potently antagonized the gastrin-elicited increase in cytosolic Ca2+ level in parietal cell enriched suspension. In ethanol induced gastric lesions in rats, rohitukine significantly inhibited the formation of erosions and increased PGE2 content showing more potency than reference drug sucralfate. Our results thus suggest that rohitukine possess significant anti-ulcer and anti-gastrinic activity in rats. It is likely that gastro-protective influences of rohitukine are dependent partly on its acid-lowering potential and partly on cytoprotective property. The acid-reducing effect of rohitukine might be attributed to its lowering effect on gastrin production and/or antagonism of gastrin evoked functional responses of parietal cells. Thus, rohitukine represent a useful agent in the treatment of peptic ulcer disease.
