Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.
Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC₅₀ value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice.
Department of Pharmacy, Kunming General Hospital of Chengdu Military Region, 212 Da-Guan Road, Kunming 650032, PR China.
Tun-Yu
TY
Jian
Jian-Chang
JC
He
Gong-Hao
GH
He
En-Fu
EF
Feng
Hong-Liang
HL
Li
Min
M
Bai
Gui-Li
GL
Xu
D000818:Animals; D047310:Apigenin / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D049919:Erigeron / Q000737:chemistry; D005260:Female; D005965:Glucuronates / Q000008:administration & dosage / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010615:Phenacetin / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D003580:Cytochromes; D004791:Enzyme Inhibitors; D005965:Glucuronates; C484876:scutellarin; D047310:Apigenin; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin