In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1

BMC Complementary Medicine and Therapies

Shasha Han¹  Na Liu¹  Ping Chen¹  Junxia Sun¹  Xiaojun Du² 

[1] Department of Ophthalmology, Dongying People’s Hospital, No. 317, Nanyi Road, Dongcheng, 257091, Dongying, Shandong Province, China;Department of Ophthalmology, Shengli Oilfield Central Hospital, 257034, Dongying, Shandong, China;

关键词: Obtusofolin;    Cytochrome P450 enzymes;    Dose-dependent;    Time-dependent;    Drug-drug interaction;   

DOI  :  10.1186/s12906-021-03397-w

来源: Springer

【 摘 要 】

BackgroundObtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin.MethodsThe effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 μM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver–Burk plots to characterize the specific inhibition model and kinetic parameters.ResultsObtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 μM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 μM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 μM− 1 and the Kinact value of 0.0515 min− 1.ConclusionsThe in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

【 授权许可】

CC BY