Comparison between Chinese medical herb Pueraria lobata crude extract and its main isoflavone puerarin - Antioxidant properties and effects on rat liver CYP-catalysed drug metabolism

Ge-gen (Radix Puerariae; RP) is used in traditional oriental medicine for v arious medicinal purposes. The drug is the root of a wild leguminous creepe r, Pueraria lobata (Willd) Ohwi. It possesses a high content of flavonoid d erivatives, the most abundant of which is puerarin (PU). Here, using the en hanced chemiluminescence technique based on horseradish peroxidase and a lu minol-oxidant-enhancer reagent, we evaluated in vitro the antioxidant activ ity of PU and RP crude extract. Both biological samples inhibited the stead y-state chemiluminescent. reaction in a dose-dependent fashion. However, di fferent inhibition mechanism were postulated, since only RP behaved like co nventional antioxidants. This activity was supposed to be due the presence of compounds other than PU in the crude extract. Using each of the specific substrates to different cytochrome P450 (CYP) isoforms or the regio- and s tereo-selective hydroxylation of testosterone as polyfunctional probe we fo und that when intragastrically administered in male Wistar rats, PU (100 or 200 mg/kg b.w.) acid RF (700 or 1,400 mg/kg b.w.) significantly altered he patic CYP-linked monooxygenases, While both CYP content and NADPH-(CYP)-c-r eductase activity were significantly increased in all situations, a complex pattern of CYP modulation was observed, including both induction (PU: CYP2 Al, 1 Al/2, 3A1, 2C11; RP: CYP1A2, 3A1, 2B1) and inactivation (PU and RP: C YP3A, 2E1, 2B1), the latter being due to either parental agents or metaboli tes, as demonstrated by in vitro studies. Overall,these findings indicate t hat RP contains compounds with potent antioxidant activity and that both PU and RP impairs CYP-catalysed drug metabolism. (C) 2000 Elsevier Science In c. All rights reserved.