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: kaempferol-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 vitro. The most potent compounds were nepetin (non-enzymic lipid peroxidation) and morelloflavone (enzymic lipid peroxidation) with IC50's in the micromolar range. Some of the compounds behaved as scavengers of hydroxyl radical in the deoxyribose degradation assay, with a calculated 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 xanthine oxidase activity, whereas morelloflavone acted as a scavenger of superoxide generated by hypoxanthine/xanthine oxidase. 4. Treatment of mice with scutellarein, hispidulin, nepetin and kaempferol-3-O-galactoside after bromobenzene intoxication decreased serum glumate-pyruvate transaminase activity, although only the last flavonoid was able to significantly reduce hepatic lipid peroxidation products and to increase the reduced glutathione level. In contrast, morelloflavone increased bromobenzene toxicity.
Depatamento de Farmacología, Facultad de Farmacia, Valencia, Spain.
M J
MJ
Sanz
M L
ML
Ferrandiz
M
M
Cejudo
M C
MC
Terencio
B
B
Gil
G
G
Bustos
A
A
Ubeda
R
R
Gunasegaran
M J
MJ
Alcaraz
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001969:Bromobenzenes / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*
D000975:Antioxidants; D001969:Bromobenzenes; D005419:Flavonoids; D005609:Free Radicals; D010936:Plant Extracts; D013481:Superoxides; D017665:Hydroxyl Radical