INFLUENCE OF A SERIES OF NATURAL FLAVONOIDS ON FREE-RADICAL GENERATING SYSTEMS AND OXIDATIVE STRESS

1. A series of flavonoids isolated from Indian medicinal plants: kaemp ferol-3-O-galactoside, hispidulin, nepetin, scutellarein, scutellarein -7-O-glucuronide, hibifolin and morelloflavone were studied for their activity as inhibitors of microsomal lipid peroxidation and scavengers of oxygen free radicals in vitro as well as in a model of xenobiotic toxicity in mouse. 2. All compounds inhibited lipid peroxidation in vi tro. The most potent compounds were nepetin (non-enzymic lipid peroxid ation) and morelloflavone (enzymic lipid peroxidation) with IC50's in the micromolar range. Some of the compounds behaved as scavengers of h ydroxyl radical in the deoxyribose degradation assay, with a calculate d rate constant for kaempferol-3-O-galactoside of 1.55 X 10(10)M(-1)s( -1). 3. Scutellarein and nepetin were found to be inhibitors of xanthi ne oxidase activity, whereas morelloflavone acted as a scavenger of su peroxide generated by hypoxanthine/xanthine oxidase. 4. Treatment of m ice with scutellarein, hispidulin, nepetin and kaempferol-3-O-galactos ide after bromobenzene intoxication decreased serum glumate-pyruvate t ransaminase activity, although only the last flavonoid was able to sig nificantly reduce hepatic lipid peroxidation products and to increase the reduced glutathione level. In contrast, morelloflavone increased b romobenzene toxicity.