Protective effects of polygodial and related compounds on ethanol-induced gastric mucosal lesions in rats: structural requirements and mode of action

• Published in: Bioorganic & medicinal chemistry letters 2002-02, Vol.12 (3), p.477-482
• Main Authors: Matsuda, Hisashi, Pongpiriyadacha, Yutana, Morikawa, Toshio, Kashima, Yousuke, Nakano, Kyoko, Yoshikawa, Masayuki
• Format: Article
• Language: English
• Subjects: Animals; Anti-Ulcer Agents - chemical synthesis; Anti-Ulcer Agents - chemistry; Anti-Ulcer Agents - pharmacology; Biological and medical sciences; Central Nervous System Depressants; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa - pathology; General pharmacology; Japan; Medical sciences; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Leaves - chemistry; Plants, Medicinal - chemistry; Polygonaceae - chemistry; Rats; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Stomach Ulcer - chemically induced; Stomach Ulcer - pathology; Stomach Ulcer - prevention & control; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00781-8

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 12α-acetal, and polygodial 12β-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. The MeOH ext. from the leaves of Tasmannia lanceolata was found to potently inhibit ethanol-induced gastric lesions in rats. Through bioassay-guided separation, polygodial, polygodial 12α-acetal, and polygodial 12β-acetal, and methyl isodrimeninol were isolated as the active constituents. Among them, polygodial showed very potent gastroprotective effects (ED 50=0.028 mg/kg, po) and 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 vannilloid receptors may be involved in the protective activity.