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BMC Complementary Medicine and Therapies

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Open Access 01-12-2021 | Research

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

Authors: Na Liu, Ping Chen, Xiaojun Du, Junxia Sun, Shasha Han

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Abstract

Background

Obtusofolin 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.

Methods

The 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.

Results

Obtusofolin 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 K_i value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the K_i 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 K_I value of 4.87 μM^− 1 and the K_inact value of 0.0515 min^− 1.

Conclusions

The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

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Title: In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1
Authors: Na Liu
Ping Chen
Xiaojun Du
Junxia Sun
Shasha Han
Publication date: 01-12-2021
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03397-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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