Effects of baicalein and wogonin on drug-metabolizing enzymes in C57BL/6J mice

Effects of baicalein and wogonin, the major flavonoids of Scutellariae radi x, on cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT), and glutat hione S-transferase (GST) were studied in C57BL/6J mice. One-week treatment of mice with a liquid diet containing 5 mM baicalein resulted in 29%, 14%, 36%, 28%, and 46% decreases of hepatic benzo(a)pyrene hydroxylation (AHH), benzphetamine N-demethylation (BDM), N-nitrosodimethylamine N-demethylatio n (NDM), nifedipine oxidation (NFO), and erythromycin N-demethylation (EMDM ) activities, respectively. Treatment with a liquid diet containing 5 mM wo gonin resulted in 43%, 22%, 21%, 24%, and 35% decreases of hepatic AHH, BDM , NDM, NFO, and EMDM activities, respectively. However, hepatic 7-methoxyre sorufin O-demethyiation (MROD) activity was increased and decreased by baic alein- and wogonin-treatments, respectively. Similar modulation was observe d with caffeine 3-demethylation (CDM) activity. Immunoblot analysis showed that the levels of hepatic CYP2E1 and CYP3A proteins were decreased by both baicalein- and wogonin-treatments. Hepatic CYP1A2 protein level was increa sed by baicalein but decreased by wogonin. In extrahepatic tissues, renal A HH activity was decreased by wogonin whereas pulmonary AHH, 7-ethoxyresoruf in O-deethylation (EROD), and MROD activities were increased by both flavon oids. Both baicalein and wogonin strongly increased CYP1A2 protein level in mouse lung. Hepatic and renal UGT activities toward p-nitrophenol were sup pressed by baicalein- and wogonin-treatments. However, cytosolic GST activi ty was not affected by flavonoids. These results suggest that ingestion of baicalein or wogonin can modulate drug-metabolizing enzymes and the modulat ion shows tissue specificity. (C) 2000 Elsevier Science Inc, All rights res erved.