Bioactivity-guided isolation of anti-inflammatory triterpenoids from the sclerotia of Poria cocos using LPS-stimulated Raw264.7 cells

Bioorg Chem. 2017 Feb:70:94-99. doi: 10.1016/j.bioorg.2016.11.012. Epub 2016 Nov 23.

Abstract

Poria cocos Wolf (Polyporaceae) has been used as a medicinal fungus to treat various diseases since ancient times. This study aimed to investigate the anti-inflammatory chemical constituents of the sclerotia of P. cocos. Based on bioassay-guided fractionation using lipopolysaccharide (LPS)-stimulated Raw264.7 cells, chemical investigation of the EtOH extract of the sclerotia of P. cocos resulted in the isolation and identification of eight compounds including six triterpenoids, namely poricoic acid A (1), 3-O-acetyl-16α-hydroxydehydrotrametenolic acid (2), polyporenic acid C (3), 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid (4), trametenolic acid (5), and dehydroeburicoic acid (6), as well as (-)-pinoresinol (7) and protocatechualdehyde (8). The structures of the isolated compounds were determined by spectroscopic analysis, including 1H and 13C NMR spectra, and LC/MS analysis. The anti-inflammatory activities of the isolates were evaluated by estimating their effect on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated Raw264.7 as well as on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compounds 1-5 inhibited NO production and iNOS expression in LPS-stimulated Raw264.7 cells. Among them, compound 1 exerted the highest anti-inhibitory activity and reduced PGE2 levels via downregulation of COX-2 protein expression. The findings of this study provide experimental evidence that the sclerotia of P. cocos are a potential source of natural anti-inflammatory agents for use in pharmaceuticals and functional foods. Furthermore, the most active compound 1, seco-lanostane triterpenoid, could be a promising lead compound for the development of novel anti-inflammatory agents.

Keywords: Anti-inflammation; Bioactivity-guided isolation; Polyporaceae; Poria cocos; seco-Lanostane triterpenoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Biological Products / chemistry
  • Biological Products / isolation & purification
  • Biological Products / pharmacology
  • Cyclooxygenase 2 / immunology
  • Dinoprostone / immunology
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Nitric Oxide / immunology
  • Nitric Oxide Synthase Type II / immunology
  • RAW 264.7 Cells
  • Triterpenes / chemistry*
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Wolfiporia / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Biological Products
  • Lipopolysaccharides
  • Triterpenes
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Dinoprostone