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

Bioorg Med Chem Lett. 2002 Feb 11;12(3):477-82. doi: 10.1016/s0960-894x(01)00781-8.

Abstract

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.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / chemical synthesis
  • Anti-Ulcer Agents / chemistry
  • Anti-Ulcer Agents / pharmacology*
  • Central Nervous System Depressants*
  • Dose-Response Relationship, Drug
  • Ethanol*
  • Gastric Mucosa / pathology
  • Japan
  • 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

Substances

  • Anti-Ulcer Agents
  • Central Nervous System Depressants
  • Sesquiterpenes
  • Ethanol
  • polygodial