Discovery and Activity Evaluation of the Inhibitory Effect of Four Kinds of Traditional Chinese Medicine Extracts on the CYP3A4 Enzyme

Background and Objective: Traditional Chinese medicines that have inhibitory effects on the CYP3A4 enzymes were screened and their inhibitory effects were verified with in vitro bioassay. Methods: The computer virtual screening methods, including the CYP3A4 enzyme pharmacophore model and the molecular docking method, were used to rapidly screen the potential CYP3A4 inhibitors in the Traditional Chinese Medicine Database (TCMD), and then in vitro experiments were conducted to validate the computational data. Results: A total of 413 chemical components in TCMD that have potential inhibitory effects on the CYP3A4 enzyme were screened, and four kinds of traditional Chinese medicines (Abrus precatorius, Andrographis paniculata, Angelica pubescens f. biserrata and Lithospermum erythrorhizon) contained the most potential CYP3A4 inhibitors; The results of the in vitro experiments showed that these four traditional Chinese medicine extracts all had certain degrees of inhibition on the CYP3A4 enzyme, with IC50 values of 5.15, 14.97, 15.2, and 24.21 μg/ml, respectively. Conclusion: The extracts of Abrus precatorius, Andrographis paniculata, Angelica pubescens f. biserrata and Lithospermum erythrorhizon had certain inhibitory effects on the CYP3A4 enzyme, and attention should be paid to the possible adverse reactions when they were used in combination with the CYP3A4 enzyme-substrate drugs. A combination of computational approaches might be a useful tool to identify potential inhibitors of the CYP3A4 enzyme from traditional Chinese medicine.