Protective effects of polygodial and related compounds on ethanol-induced gastric mucosal lesions in rats: structural requirements and mode of action.
The methanolic extract from the leaves of Tasmannia lanceolata was found to potently inhibit ethanol-induced gastric lesions in rats. Through bioassay-guided separation, three known sesquiterpenes, polygodial, polygodial 12 alpha-acetal, and polygodial 12 beta-acetal, and a new sesquiterpene, methyl isodrimeninol, were isolated as the active constituents. Among them, polygodial showed very potent gastroprotective effects (ED(50)=0.028 mg/kg, po). From the gastroprotective effects of various reduction and oxidation derivatives of polygodial, the dialdehyde or diacetal structure was found to be essential for the strong activity. Since the gastroprotection of polygodial was attenuated by pretreatment with indomethacin, N-ethylmaleimide, N(G)-nitro-L-arginine methyl ester and ruthenium red, endogenous prostaglandins, sulfhydryl compounds, nitric oxide and vanilloid receptors may be involved in the protective activity.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Pongpiriyadacha
Yutana
Y
Morikawa
Toshio
T
Kashima
Yousuke
Y
Nakano
Kyoko
K
Yoshikawa
Masayuki
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002492:Central Nervous System Depressants; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005753:Gastric Mucosa / Q000473:pathology; D007564:Japan; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D019664:Polygonaceae / Q000737:chemistry; D051381:Rats; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D002492:Central Nervous System Depressants; D012717:Sesquiterpenes; D000431:Ethanol; C034380:polygodial