title: Effects of brucine combined with glycyrrhetinic acid or liquiritin on rat hepatic cytochrome P450 activities in vivo.
abstract: Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg.kg-1 per day) and the high dose of BR combined with glycyrrhetinic acid (GA, 25 mg.kg-1 per day) or liquiritin (LQ, 20 mg.kg-1 per day) for 7 consecutive days. Compared with the control, brucine caused 24.5% and 34.6% decrease of CYP3A-associated testosterone 6beta-hydroxylation (6betaTesto-OH) and CYP2C-associated tolbutamide hydroxylation (Tol-OH), respectively, and 146.1% increase of CYP2El-associated para-nitrophenol hydroxylation (PNP-OH) at the high dose level. On the other hand, (BR+GA) caused 51.4% and 33.5% decrease, respectively, of CYP2El-associated PNP-OH and CYP1A2-associated ethoxyresorufin-O-de-ethylation (EROD) as compared with the high dose of BR group. Meanwhile, (BR+LQ) caused 41.1% decrease of CYP2El-associated PNP-OH and 37.7% increase of CYP2C-associated Tol-OH. The results indicated that the co-administration of BR with GA or LQ had effect on mRNA expression and activities of the CYP450 enzymes mentioned above to some extent, and the in vivo antagonism of LQ on BR-induced CYPs adverse effects and the in vivo inhibitory action of GA on CYP2E1 and 1A2 might play an important role in the detoxification of Radix Glycyrrhizae against Strychnos nux-vomica L.
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei University, Wuhan 430062, China.
authors.forename: Pan-pan
authors.initials: PP
authors.lastname: Xing
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.forename: Feng-mei
authors.initials: FM
authors.lastname: Han
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D044950:Flavanones / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D005960:Glucosides / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009596:Nitrophenols / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013331:Strychnine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D031461:Strychnos nux-vomica / Q000737:chemistry; D014044:Tolbutamide / Q000378:metabolism
chemical_list: D044950:Flavanones; D005960:Glucosides; D009596:Nitrophenols; D012333:RNA, Messenger; C083806:brucine; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; C022657:steroid hormone 6-beta-hydroxylase; D013331:Strychnine; D006034:Glycyrrhetinic Acid; C512196:liquiritin