Asia Pacific Academy of Science Pte. Ltd. (APACSCI) specializes in international journal publishing. APACSCI adopts the open access publishing model and provides an important communication bridge for academic groups whose interest fields include engineering, technology, medicine, computer, mathematics, agriculture and forestry, and environment.
Effects of three Chinese patent medicines against cardiovascular diseases on the in vitro activities of rat liver microsomal CYP450 four subtypes
Vol 3, Issue 1, 2022
VIEWS - 3165 (Abstract)
Download PDF
Abstract
Objective: To evaluate the effects of Shensong Yangxin capsule, Qiliqiangxin capsule and Tongmai Yangxin Pill on the in vitro activities of four subtypes of rat liver microsomal CYP450 enzyme CYP1A2, CYP2C11, CYP2D1 and CYP3A1. Method: 15.04 μmol·L-1 caffeine, 4.98 μmol·L-1 omeprazole, 7.81 μmol·L-1 metoprolol and 6 μmol·L-1 midazolam is the specific probe substrate of CYP1A2, CYP2C11, CYP2D1 and CYP3A1 respectively. Three Chinese patent medicines against cardiovascular diseases are co incubated with the mixed probe substrate of four CYP450 enzyme subtypes in rat liver microsomes respectively. The remaining probe substrate in rat liver microsomes incubation system is measured by HPLC to calculate the inhibition percentage of corresponding enzyme activity and calculate the IC50 value. Results: compared with the blank group, the activities of sub enzymes decreased with the increase of the concentration of three drugs (P < 0.05); The IC50 values of three drugs on rat liver microsomal CYP1A2, CYP2C11, CYP2D1 and CYP3A1 were 1.896, 31.97, 12.37 and 1.357 respectively μmol·L-1; Qiliqiangxin capsule>100, 1.513, 35.2, 6.669 μmol·L-1; Tongmai Yangxin pill>100, 33.970, 0.566, 14.380 μmol·L-1 . Conclusion: Shensong Yangxin capsule has moderate inhibitory effect on CYP1A2 and CYP3A1, Qiliqiangxin capsule has moderate inhibitory effect on CYP2C11 and CYP3A1, Tongmai Yangxin pill has strong inhibitory effect on CYP2D1, and other effects are not obvious.
Keywords
References
1. Ge J, Xu Y, Wang C. Internal medicine. Beijing: People’s Health Publishing House; 2019. pp. 170-226.
2. Yao J, Lv S, Wang R. Application of new dosage forms of slow and controlled release and targeted drug delivery in cardiovascular traditional Chinese medicine. Chinese herbal medicine. 2014; 45(12): 1809-1812.
3. Dong Y, Wang J, Yang Q, et al Overview of research on the interaction between CYP450 enzyme and metabolism of traditional Chinese medicine. Chinese Journal of traditional Chinese medicine information. 2011; 18(1): 100-103.
4. Pan J, Lu Y, Sun J, et al. Inhibitory effect of Aidi Injection on CYP450 enzyme in human and rat liver microsomes in vitro. Chinese patent medicine. 2016; 38(11): 2332-2237.
5. PI Rongbiao Basis and practice of drug screening and drug evaluation. Guangzhou: Sun Yat sen University Press; 2019. pp. 60-61.
6. Guengerich FP. Cytochrome P450s and other enzymes in drug metabolism and toxicity. The AAPS Journal. 2006; 8(1): E101-E111. doi: 10.1208/aapsj080112
7. Chen W. “Cocktail” probe drug method to evaluate the effect of neogambogic acid on the metabolic activities of different subtypes of cytochrome P450 in rat liver microsomes. Hefei: Anhui University of traditional Chinese medicine. 2016.
8. FDA, Center for Drug Evaluation and Research, Center for Biological Evaluation and Research, et al. Guidance for industry: in vivo drug metabolism/ drug interaction studies study design data analysis and recommendations for dosing and labeling. Rockville: Federal Register; 1999.
9. Yao M, Zhu M, Sinz MW, et al. Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC–MS/MS analysis. Journal of Pharmaceutical and Biomedical Analysis. 2007; 44(1): 211-223. doi: 10.1016/j.jpba.2007.02.034
10. Fan Z, Ma S, Xu A, et al. Effects of three traditional Chinese medicine components on CYP2C9 enzyme. Medical Herald. 2019; 38(4): 486-490.
11. Jia Y, Shen J, Xie H, et al. Inhibitory effect of gastrodin on human liver microsomal cytochrome P450 enzyme. Chinese Journal of clinical pharmacology and therapeutics. 2016; 21(2): 134-138.
12. Giri P, Patel H, Srinivas NR. Use of Cocktail Probe Drugs for Indexing Cytochrome P450 Enzymes in Clinical Pharmacology Studies—Review of Case Studies. Drug Metabolism Letters. 2019; 13(1): 3-18. doi: 10.2174/1872312812666181119154734
13. Ma Z, Wang Y, Tan H, et al Interaction between traditional Chinese medicine and liver drug metabolizing enzymes. World Chinese Journal of digestion. 2016; 24(7): 994-1001.
14. Wu B, Liu P, Gao Y, et al. Regulation of aqueous extracts of wild jujube kernel, Polygala tenuifolia and Platycodon grandiflorum on CYP450 enzyme activity and mrna expression in rat liver. Chinese Journal of experimental prescriptions. 2011; 17(18): 235-239.
15. Shi L, Zhang Y, Wang E, et al. Inhibitory effect of gallic acid and its oxidation products on CYP3A in rat liver microsomes. Journal of the Third Military Medical University. 2014; 36(2): 130-134.
16. Xiao Y, Jiang Z, Yao J, et al. Investigation of Picroside II’ s impacts on the P450 activities using a cocktail method. Chin J Nat Med. 2008; 6(4): 292-297.
17. Yi J, Wu B, Liu C, et al. Effects of total ginsenosides on γ Study on the regulation of P450 enzyme in rat liver after X-ray irradiation. Chinese Journal of traditional Chinese medicine. 2015; 40(20): 4037-4043.
18. Wang X, Cheung CM, Lee WYW, et al. Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine. 2010; 17(11): 868-875. doi: 10.1016/j.phymed.2010.05.003
19. Liu L, Xiao J, Peng Z, et al. Metabolism of glycyrrhetinic acid in vitro in human cytochrome CYP450. Journal of pharmacy. 2011; 46(01): 81-87.
20. Chen H, Zhang X, Feng Y, et al. Bioactive components of Glycyrrhiza uralensis mediate drug functions and properties through regulation of CYP450 enzymes. Molecular Medicine Reports. 2014; 10(3): 1355-1362. doi: 10.3892/mmr.2014.2331
Refbacks
- There are currently no refbacks.
Copyright (c) 2022 Rurun Huang, Jiao Yang, Shan Liu, Yucheng Mu, Yong Lai
This work is licensed under a Creative Commons Attribution 4.0 International License.
This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Prof. Prakash Deedwania
University of California,
San Francisco, United States
