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Review
. 2022 Jan 14;27(2):515.
doi: 10.3390/molecules27020515.

Enzyme Activity of Natural Products on Cytochrome P450

Hua-Li Zuo  1   2   3 , Hsi-Yuan Huang  1   2 , Yang-Chi-Dung Lin  1   2 , Xiao-Xuan Cai  1 , Xiang-Jun Kong  4 , Dai-Lin Luo  1 , Yu-Heng Zhou  1 , Hsien-Da Huang  1   2
Affiliations
Review

Enzyme Activity of Natural Products on Cytochrome P450

Hua-Li Zuo et al. Molecules. .

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.

Keywords: combinatorial synergism; cytochrome P450; herbal ingredient; herb–drug interaction; herb–herb interaction; natural product.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
PRISMA flow diagram detailing the number of papers included at each stage and the reasons for removal. Please see Supplementary File S1 for detail.
Figure 2
Figure 2
Publications (research articles and reviews) reporting the activity of natural products on CYP450s.
Figure 3
Figure 3
Geographical coverage of papers reporting the activity of natural products on CYP450s, and the top 10 countries ranked by the number of papers.
Figure 4
Figure 4
Number of papers reporting the modulation effects of natural resources on each CYP450 enzyme.
Figure 5
Figure 5
The number of research articles reporting the CYP450s’ modulation effects of the most popular natural products.
See this image and copyright information in PMC

References

    1. Hitchings R., Kelly L. Drug metabolism as a community effort. Cell Metab. 2019;30:235–237. doi: 10.1016/j.cmet.2019.07.005. - DOI - PubMed
    1. Rendic S., Guengerich F.P. Survey of human oxidoreductases and cytochrome P450 enzymes involved in the metabolism of xenobiotic and natural chemicals. Chem. Res. Toxicol. 2015;28:38–42. doi: 10.1021/tx500444e. - DOI - PMC - PubMed
    1. Rendic S.P., Guengerich F.P. Human cytochrome P450 enzymes 5–51 as targets of drugs and natural and environmental compounds: Mechanisms, induction, and inhibition–toxic effects and benefits. Drug Metab. Rev. 2018;50:256–342. doi: 10.1080/03602532.2018.1483401. - DOI - PMC - PubMed
    1. Ji S., He D.D., Su Z.Y., Du Y., Wang Y.J., Gao S.K., Guo M.Z., Tang D.Q. P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs: A strategy to explore compatibility mechanism of Sangju-Yin. Phytomedicine. 2019;58:152866. doi: 10.1016/j.phymed.2019.152866. - DOI - PubMed
    1. Ma W.J., Wang W., Huang X.H., Yao G.Z., Jia Q., Shen J.Y., Ouyang H.Z., Chang Y.X., He J. HPLC-MS/MS analysis of Aconiti Lateralis Radix praeparata and its combination with Red Ginseng effect on rat CYP450 activities using the cocktail approach. Evid. Based Complement. Alternat. Med. 2020;2020:8603934. doi: 10.1155/2020/8603934. - DOI - PMC - PubMed

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