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

A simultaneous quantitative analytical method for 13 stilbenoids including (-)-hopeaphenol (), (+)-isohopeaphenol (), hemsleyanol D (), (-)-ampelopsin H (), vaticanols A (), E (), and G (), (+)-α-viniferin (), pauciflorol A (), hopeafuran (), (-)-balanocarpol (), (-)-ampelopsin A (), and -resveratrol 10--β-d-glucopyranoside (), and two dihydroisocoumarins, phayomphenols A₁ () and A₂ () in the extract of (dipterocarpaceae) was developed. According to the established protocol, distributions of these 15 polyphenols (-) in the bark and wood parts of and a related plant were evaluated. In addition, the principal polyphenols (, , , -) 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 (, , and ) 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.