枸杞多糖对大鼠CYP450酶的调控作用

doi:10.3969/j.issn.2095-9400.2020.03.011

Abstract
Figure/Table
References (0)
Related Citation (15)

Download: PDF (1711 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To evaluate the regulating effect of LyciumBarbarum polysaccharides (LBP) on activities and mRNA expressions of cytochrome P450 (CYP450) in rats. Methods: SD rats were randomly divided as test group (low-dose group, high-dose group) and control group. Treated with LBP and given pure water respectively for 14 days, the test group and control group were simultaneously given the mixture of four probes on day 15. Plasma concentration of probes was determined at a series of time-points after dosing. The activities of CYP450 were evaluated according to the pharmacokinetic parameters of corresponding probes. Real-time PCR was applied to assess the mRNA levels of CYP450. Results: Compared with control group, CLz/F of tolbutamide in high dose group rats decreased by 27%, AUC(0-t) and Cmax increased by 50% and 28%; CLz/F and Vz/F of midazolam in low dose group rats decreased by 25% and 35%, AUC(0-t) increased by 38%; CLz/F and Vz/F of midazolam inhigh dose group rats decreased by 34% and 38%, while AUC(0-t), Tmax and Cmax increased by 51%, 50% and 65%, respectively. In addition, treatment with LBP significantly down-regulated the mRNA expressions of CYP2C11 in high dose group and CYP3A1 in both low and high dose groups by 56%, 44% and 68% respectively. LBP had no impact on pharmacokinetics of phenacetin, bupropion and mRNA expressions of CYP1A2, CYP2B1. Conclusion: LBP can down-regulate the activities and mRNA expressions of CYP2C11 and CYP3A1.

Key words： LyciumBarbarum polysaccharides CYP450 activity mRNA expression modulation rats

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	HUANG Aifang
	WANG Chenxiang
	JIN Hui
	YE Qizhen
	JIN Mi
	ZHOU Ziye

URL:

https://xb.wmu.edu.cn/EN/10.3969/j.issn.2095-9400.2020.03.011 OR https://xb.wmu.edu.cn/EN/Y2020/V50/I3/221

[1] CHEN Q, WEI D Q. Human cytochrome P450 and personalized medicine[J]. Adv Exp Medbiol, 2015, 827: 341-351.
[2] ZAKIA B. Role of cytochrome P450 in drug interactions[J]. Nutr Metab, 2008, 5: 27.
[3] ARAYNE M S, SULTANA N, BIBI Z. Grape fruit juice-drug interactions[J]. Pak J Pharm Sci, 2005, 18(4): 45-57.
[4] COLOMBO D, LUNARDON L, BELLIA G. Cyclosporine and herbal supplement interactions[J]. Int J Toxicol, 2014, 2014: 145325.
[5] HEBERT M F, PARK J M, CHEN Y L, et al. Effect of St.John’s wort on tacrolimus pharmacokinetics in healthy volunteers[J]. J Clin Pharmacol, 2004, 44(1): 89-94.
[6] JIANG X, WILLIAMS K M, LIAUW W S, et al. Effect of St.John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects[J]. Brit J Clin Pharmacol, 2004, 57(5): 592-599.
[7] MURPHY P A, KERN S E, STANCZY F Z, et al. Interactions of St.John’s wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinylestradiol, ovarian activity and breakthrough bleeding[J]. Contraception, 2005, 71(6): 402-408.
[8] 魏永祥, 商希礼. 枸杞多糖的研究进展[J]. 安徽农业科学, 2010, 38(11): 5834-5836.
[9] 孙桂菊, 左平国. 枸杞多糖功效研究及应用状况[J]. 东南大学学报, 2010, 29(2): 209-215.
[10] LEWIS DFV, ITO Y, GOLDFARB P S. Cytochrome P450 structures and their substrate interactions[J]. Drug Develop Res, 2005, 66(1): 19-24.
[11] ZHANG S, SONG N, LI Q, et al. Liquid chromatography/tandem mass spectrometry method for simultaneous evaluation of activities of five cytochrome P450s using a five-drug cocktail and application to cytochrome P450 phenotyping studies in rats[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2008, 871(1): 78-89.
[12] JURICA J, KYR M, MCCASKEY HADASOVA E, et al. Evaluation of the activity of P450 enzymes in rats: use of the single marker or combined drug administration[J]. Neuro Endocrinol Lett, 2009, 30(1): 92-95.
[13] 黄爱芳, 王陈翔, 周晓洁, 等. 土忍翘薇合剂对大鼠CYP450酶活力和mRNA的调控作用[J]. 温州医科大学学报, 2018, 48(1): 57-62.
[14] JARRAR Y B, LEE S J. Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy[J]. Drug Metabol Drug Interact, 2014, 29(4): 211-220.
[15] LEUNG H, HUNG A, HUI A C, et al. Warfarin overdose due to the possible effects of Lyciumbarbarum L[J]. Food ChemToxicol, 2008, 46(5): 1860-1862.
[16] RIVERA C A, FERRO C L, BURSUA A J, et al. Probable interaction between Lyciumbarbarum (goji) and warfarin[J]. Pharmacotherapy, 2012, 32(3): e50-e53.
[17] YU J, PETRIE I D, LEVY R H, et al. Mechanisms and clinical significance of pharmacokinetic-based drug-drug interactions with drugs approved by the us food and drug administration in 2017[J]. Drug Metab Dispos, 2019, 47(2): 135-144.