Enzyme Activity of Natural Products on Cytochrome P450.

Hua-Li Zuo,Hsi-Yuan Huang,Yu-Heng Zhou,Xiang-Jun Kong,Yang-Chi-Dung Lin,Hsien-Da Huang,Dai-Lin Luo,Xiao-Xuan Cai

doi:10.3390/molecules27020515

Abstract

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb–herb or herb–drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals’ effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

Highlights

Absorption, distribution, metabolism, and excretion (ADME) is a pretty complex process that a drug will go through
We further excluded 1780 articles for reasons including the papers published in the journal without an impact factor (n = 68); these papers were published neither as research articles nor as review articles (n = 57); their topics were not relevant to the effects of natural products on the enzyme activity of cytochrome P450 (CYP450) (n = 1549), the results were stated in research articles without experimental validation (n = 28), and some other reasons (n = 22)
Induce (The results suggested that multiple dose administration of Danshen capsules could induce cytochrome P450 (CYP) isoenzymes, thereby increasing the clearance of clopidogrel.)

Summary

Introduction

Absorption, distribution, metabolism, and excretion (ADME) is a pretty complex process that a drug will go through. Drug metabolism plays a pivotal role in determining the fate of drugs. Drug-metabolizing enzymes (DMEs) can convert drugs/compounds to metabolites with different biological effects and are critical in determining the bio-availability and effectiveness of orally administered drugs [1]. The CYP450 catalyzes the phase I metabolism of conventional drugs. The activity of CYP450s could be inhibited or induced by various xenobiotics (e.g., herbal ingredients), which will eventually be responsible for the most metabolism-based herb–herb or herb–drug interactions. Compounds from herbal or natural products are frequently involved in such interactions

Methods

Results

Conclusion