Gastroprotective effects of phenylpropanoids from the rhizomes of Alpinia galanga in rats: structural requirements and mode of action.

The effects of 1'S-1'-acetoxychavicol acetate and related phenylpropanoids isolated from the rhizomes of Alpinia galanga on ethanol-induced gastric lesions in rats were examined. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate markedly inhibited the ethanol-induced gastric mucosal lesions (ED(50)=0.61 and ca. 0.90 mg/kg). In addition, 1'S-1'-acetoxychavicol acetate inhibited the lesions induced by 0.6 M HCl (ED(50)=0.73 mg/kg) and aspirin (ED(50)=0.69 mg/kg) but it did not show a significant effect on indomethacin-induced gastric lesions and acid output in pylorus-ligated rats at doses of 0.5-5.0 mg/kg. From the gastroprotective effects of various related compounds, the 1'-acetoxyl group of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate was found to be essential for their strong activity. With regard to the mode of action, the gastroprotective effects of 1'S-1'-acetoxychavicol acetate were attenuated by pretreatment with indomethacin and N-ethylmaleimide, and 1'S-1'-acetoxychavicol acetate significantly increased the glutathione levels of gastric mucosa in rats. These findings suggest that endogenous prostaglandins and sulfhydryl compounds are involved in the protective effect of 1'S-1'-acetoxychavicol acetate.