Effects of baicalein and wogonin on drug-metabolizing enzymes in C57BL/6J mice.
Effects of baicalein and wogonin, the major flavonoids of Scutellariae radix, on cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT), and glutathione 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-demethylation (NDM), nifedipine oxidation (NFO), and erythromycin N-demethylation (EMDM) activities, respectively. Treatment with a liquid diet containing 5 mM wogonin resulted in 43%, 22%, 21%, 24%, and 35% decreases of hepatic AHH, BDM, NDM, NFO, and EMDM activities, respectively. However, hepatic 7-methoxyresorufin O-demethylation (MROD) activity was increased and decreased by baicalein- and wogonin-treatments, respectively. Similar modulation was observed 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 increased by baicalein but decreased by wogonin. In extrahepatic tissues, renal AHH activity was decreased by wogonin whereas pulmonary AHH, 7-ethoxyresorufin O-deethylation (EROD), and MROD activities were increased by both flavonoids. Both baicalein and wogonin strongly increased CYP1A protein level in mouse lung. Hepatic and renal UGT activities toward p-nitrophenol were suppressed by baicalein- and wogonin-treatments. However, cytosolic GST activity was not affected by flavonoids. These results suggest that ingestion of baicalein or wogonin can modulate drug-metabolizing enzymes and the modulation shows tissue specificity.
Ueng
Y F
YF
National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC. ueng@cma23.nricm.edu.tw
Shyu
C C
CC
Lin
Y L
YL
Park
S S
SS
Liao
J F
JF
Chen
C F
CF
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology
D044950:Flavanones; D005419:Flavonoids; D007527:Isoenzymes; D018336:Receptors, Aryl Hydrocarbon; C006680:baicalein; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; C085514:wogonin