LICORICE EXTRACT AND ITS MAJOR POLYPHENOL GLABRIDIN PROTECT LOW-DENSITY-LIPOPROTEIN AGAINST LIPID-PEROXIDATION - IN-VITRO AND EX-VIVO STUDIES IN HUMANS AND IN ATHEROSCLEROTIC APOLIPOPROTEIN E-DEFICIENT MICE

Polyphenolic flavonoids are powerful antioxidants. In the present stud y we investigated the antioxidative activity against low-density-lipop rotein (LDL) oxidation of a not yet studied subclass of polyphenols, t he isoflavans, which are present in licorice alcoholic extract. The st udy was performed in humans as well as in atherosclerotic apolipoprote in E-deficient mice (EO), because their LDL is highly susceptible to o xidation. LDL oxidation was induced by incubating it with copper ions as well as with the aqueous or lipid-soluble free radical generators 2 ,2'-azobis'2-amidino propane hydrochloride (AAPH) and 2,2'-azobis 2,4- dimethylvaleronitrile (AMVN), respectively. The extent of LDL oxidatio n was determined by measuring the formation of conjugated dienes, thio barbituric acid reactive-substances (TEARS), and lipid peroxides. By a ll methods in human studies, licorice ethanolic extract as well as a p ure material, which was identified by gas chromatography-mass spectros copy as the isoflavan glabridin, were shown to inhibit LDL oxidation b y a mechanism involving scavenging of free radicals. In an ex vivo stu dy, LPL isolated from the plasma of 10 normolipidemic subjects who wer e orally supplemented for 2 wk with 100 mg licorice/d was more resista nt to oxidation than was LDL isolated before licorice supplementation. Dietary supplementation of each E-0 mouse with licorice (200 mu g/d) or pure glabridin (20 mu g/d) for 6 wk resulted in a substantial reduc tion in the susceptibility of their LDL to oxidation along with a redu ction in the atherosclerotic lesion area. These results could be relat ed to the absorption and binding of glabridin to the LDL particle and subsequent protection of the LDL from oxidation by multiple modes as s hown in humans and in E-0 mice.