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Scutellarin Inhibits Cytochrome P450 Isoenzyme 1A2 (CYP1A2) in Rats
Author(s) -
Jian TunYu,
He JianChang,
He GongHao,
Feng EnFu,
Li HongLiang,
Bai Min,
Xu GuiLi
Publication year - 2012
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3723
Subject(s) - scutellarin , cyp1a2 , pharmacology , in vivo , chemistry , microsome , medicine , biochemistry , in vitro , biology , microbiology and biotechnology
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 µ m ) decreased the formation of 4‐acetamidophenol in a concentration‐dependent manner, with an IC 50 value of 108.20 ± 0.657 µ m . 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 µ m . 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. Copyright © 2012 John Wiley & Sons, Ltd.