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.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Pongpiriyadacha
Yutana
Y
Morikawa
Toshio
T
Ochi
Momotaro
M
Yoshikawa
Masayuki
M
D000284:Administration, Oral; D032429:Alpinia / Q000737:chemistry; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D001592:Benzyl Alcohols; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D005033:Ethylmaleimide / Q000008:administration & dosage / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D015394:Molecular Structure; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010437:Peptic Ulcer / Q000139:chemically induced / Q000188:drug therapy; D010666:Phenylpropionates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000008:administration & dosage / Q000493:pharmacokinetics
D001592:Benzyl Alcohols; D004365:Drugs, Chinese Herbal; D005765:Gastrointestinal Agents; D010666:Phenylpropionates; D010936:Plant Extracts; D013729:Terpenes; D000431:Ethanol; D005033:Ethylmaleimide; D001241:Aspirin; C047948:1'-acetoxychavicol acetate; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin