Quantitative Determination of Stilbenoids and Dihydroisocoumarins in Shorea roxburghii and Evaluation of Their Hepatoprotective Activity

Int J Mol Sci. 2017 Feb 20;18(2):451. doi: 10.3390/ijms18020451.

Abstract

A simultaneous quantitative analytical method for 13 stilbenoids including (-)-hopeaphenol (1), (+)-isohopeaphenol (2), hemsleyanol D (3), (-)-ampelopsin H (4), vaticanols A (5), E (6), and G (7), (+)-α-viniferin (8), pauciflorol A (9), hopeafuran (10), (-)-balanocarpol (11), (-)-ampelopsin A (12), and trans-resveratrol 10-C-β-d-glucopyranoside (13), and two dihydroisocoumarins, phayomphenols A₁ (14) and A₂ (15) in the extract of Shorea roxburghii (dipterocarpaceae) was developed. According to the established protocol, distributions of these 15 polyphenols (1-15) in the bark and wood parts of S. roxburghii and a related plant Cotylelobium melanoxylon were evaluated. In addition, the principal polyphenols (1, 2, 8, 13-15) exhibited hepatoprotective effects against d-galactosamine (d-galN)/lipopolysaccharide (LPS)-induced liver injury in mice at a dose of 100 or 200 mg/kg, p.o. To characterize the mechanisms of action, the isolates were examined in in vitro studies assessing their effects on (i) d-GalN-induced cytotoxicity in primary cultured mouse hepatocytes; (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages; and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. The mechanisms of action of these polyphenols (1, 2, and 8) were suggested to be dependent on the inhibition of LPS-induced macrophage activation and reduction of sensitivity of hepatocytes to TNF-α. However, none of the isolates reduced the cytotoxicity caused by d-GalN.

Keywords: Shorea roxburghii; dihydroisocoumarin; hepatoprotective effect; mechanism of action; quantitative analysis; stilbenoid.

MeSH terms

  • Animals
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Dipterocarpaceae / chemistry*
  • Disease Models, Animal
  • Galactosamine / adverse effects
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Isocoumarins / chemistry
  • Isocoumarins / pharmacology*
  • Lipopolysaccharides / adverse effects
  • Liver / drug effects
  • Liver / metabolism
  • Liver Diseases / drug therapy
  • Liver Diseases / etiology
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Nitric Oxide / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Polyphenols / chemistry
  • Polyphenols / pharmacology
  • Protective Agents / chemistry
  • Protective Agents / pharmacology*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Isocoumarins
  • Lipopolysaccharides
  • Plant Extracts
  • Polyphenols
  • Protective Agents
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Galactosamine