Bioactive constituents of Chinese natural medicines. III. Absolute stereostructures of new dihydroflavonols, hovenitins I, II, and III, isolated from hoveniae semen seu fructus, the seed and fruit of Hovenia dulcis THUNB. (Rhamnaceae): inhibitory effect on alcohol-induced muscular relaxation and hepatoprotective activity

Abstract

The methanol-soluble fraction from a Chinese natural medicine Hoveniae Semen Seu Fructus, the seed and fruit of Hovenia dulcis THUNB. (Rhamnaceae) was found to show an inhibitory effect on the alcohol-induced muscular relaxation and a protective activity on the D-galactosamine/lipopolysaccharide or carbon tetrachloride-induced liver injury. Through bioassay-guided separation using a traction performance test, three new dihydrofravonols named hovenitins I, II, and III were isolated from Hoveniae Semen Seu Fructus together with four known flavonoids, (+)-ampelopsin, laricetrin, myricetin, and (+)-gallocatechin. The absolute stereostructures of hovenitins I, II, and III were determined on the basis of chemical and physicochemical evidence to be (2R, 3R)-5,7,4',5'-tetrahydroxy-3'-methoxydihydroflavonol, (2R,3S)-5,7,4',5'-tetrahydroxy-3'-methoxy-dihydroflavonol, and (2R, 3S)-5,7,3',4',5'-pentahydroxydihydro-flavonol, respectively. Hovenitin I and (+)-ampelopsin, both of which were principal ingredients of the active fractions from this natural medicine, were found to show an inhibitory activity on the ethanol-induced muscle relaxation in rats. In addition, hovenitin I showed a protective activity on the liver injury induced by D-galactosamine/lipopolysaccharide or carbon tetrachloride in mice.