In Vitro Inhibitory Effects of Scutellarin on Six Human/Rat Cytochrome P450 Enzymes and P-glycoprotein

Molecules

Yong-Long Han¹  Dan Li¹  Quan-Jun Yang¹  Zhi-Yong Zhou¹  Li-Ya Liu¹  Bin Li¹  Jin Lu¹ 

[1] Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600 Yishan Road, Shanghai 200233, China

关键词: scutellarin;    cytochrome P450;    P-glycoprotein;    herb-drug interactions;   

DOI  :  10.3390/molecules19055748

来源: mdpi

【 摘 要 】

Inhibition of cytochrome P450 (CYP) and P-glycoprotein (P-gp) are regarded as the most frequent and clinically important pharmacokinetic causes among the various possible factors for drug-drug interactions. Scutellarin is a flavonoid which is widely used for the treatment of cardiovascular diseases. In this study, the in vitro inhibitory effects of scutellarin on six major human CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and six rat CYPs (CYP1A2, CYP2C7, CYP2C11, CYP2C79, CYP2D4, and CYP3A2) activities were examined by using liquid chromatography-tandem mass spectrometry. Meanwhile, the inhibitory effects of scutellarin on P-gp activity were examined on a human metastatic malignant melanoma cell line WM-266-4 by calcein-AM fluorometry screening assay. Results demonstrated that scutellarin showed negligible inhibitory effects on the six major CYP isoenzymes in human/rat liver microsomes with almost all of the IC₅₀ values exceeding 100 μM, whereas it showed values of 63.8 μM for CYP2C19 in human liver microsomes, and 63.1 and 85.6 μM for CYP2C7 and CYP2C79 in rat liver microsomes, respectively. Scutellarin also showed weak inhibitory effect on P-gp. In conclusion, this study demonstrates that scutellarin is unlikely to cause any clinically significant herb-drug interactions in humans when co-administered with substrates of the six CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and P-gp.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.