代谢分析

5 个蒽醌三三配伍治疗脑缺血大鼠的药代动力学研究*

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  • 1.河南中医药大学, 郑州 450046;
    2.呼吸疾病中医药防治省部共建协同创新中心, 郑州 450046;
    3.郑州市中药质量控制与评价重点实验室, 郑州 450046
第一作者: Tel: 13838057402;E-mail: lirong_tg94@163.com
** Tel: 13526403080;E-mail: fengsx221@163. com

收稿日期: 2020-06-08

  网络出版日期: 2024-05-31

基金资助

* 河南省中医药大学博士基金科研项目(BSJJ-2016-01)

Pharmacokinetics of five anthraquinones when three of five were compatibly administrated to treat rats with cerebral ischemia*

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  • 1. Henan University of Chinese Medicine, Zhengzhou 450046, China;
    2. Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P. R., Zhengzhou 450046, China;
    3. Zhengzhou Key Laboratory of Chinese Medicine Quality Control and Evaluation, Zhengzhou 450046, China

Received date: 2020-06-08

  Online published: 2024-05-31

摘要

目的: 建立 LC-MS 方法测定大鼠血浆中蒽醌成分含量, 探讨5 个大黄蒽醌成分(芦荟大黄素、大黄素、大黄酸、大黄酚、大黄素甲醚)三三配伍时在脑缺血大鼠模型中的药代动力学特征。方法: MCAO 法制备大鼠局灶性脑缺血模型。模型大鼠随机分成11 组, 空白组1 组, 给药组10 组。给药组将5 个大黄蒽醌三三结合, 给药剂量: 芦荟大黄素(A)13. 05 mg·kg-1, 大黄素(B)34. 65 mg·kg-1, 大黄酸(C)17. 25mg·kg-1, 大黄酚(D)39. 45 mg·kg-1, 大黄素甲醚(E)26. 4 mg·kg-1。血浆样品经甲醇沉淀蛋白后, XBridgeTMC18 色谱柱分析, 高分辨质谱检测。流动相为甲醇-3 mmol·L-1 乙酸铵, 梯度洗脱。采用内标法测血药浓度, Kinetica 5. 0 药动学软件以非房室模型计算药代动力学参数。结果: 当与不同的2 个大黄蒽醌联用时, 芦荟大黄素、大黄素、大黄酸、大黄酚和大黄素甲醚的药代动力学参数均存在差异。结论: 本研究为这5 个大黄蒽醌的作用机制研究提供理论基础, 为其临床用药提供了实验参考。

本文引用格式

李荣荣, 赵迪, 冯素香, 郝蕊, 李焕茹, 胡雁萍, 刘学芳 . 5 个蒽醌三三配伍治疗脑缺血大鼠的药代动力学研究*[J]. 药物分析杂志, 2021 , 41(3) : 427 -435 . DOI: 10.16155/j.0254-1793.2021.03.07

Abstract

Objective: To establish a LC-MS method to determine the content of 5 rhubarb anthraquinones in rat plasma and explore their pharmacokinetic characteristics in cerebral ischemia-reperfusion model rats when three kinds of the five anthraquinones were administrated in compatibility. Methods: A MCAO method was developed to establish focal cerebral ischemia rat model. The model rats were randomly divided into 11 groups, a blank group and the other 10 drug administration groups. In the drug administration group, three of five were compatibly administrated to treat rats with cerebral ischemia. Administration dose: aloe-emodin(A)13. 05 mg·kg-1, emodin(B)34. 65 mg·kg-1, rhein(C)17. 25 mg·kg-1, chrysophanol(D)39. 45 mg·kg-1, physcion(E) 26. 4 mg·kg-1. Plasma samples were precipitated with alcohol, analyzed on a XBridgeTMC18 column and detected using high-resolution mass spectrometry. The mobile phase was methanol-3 mmol·L-1 ammonium acetate with gradient elution. And the plasma concentration was measured by internal standard method, and Kinetica 5. 0 pharmacokinetic software was applied to calculate the pharmacokinetic parameters with non-compartmental model. Results: When combined with two different rhubarb anthraquinones, the pharmacokinetic parameters of aloe-emodin, emodin, rhein, chrysophanol and physcion were all discrepant. Conclusion: This study provides a theoretical basis for the research on the mechanism of action of these five rhubarb anthraquinones, and provides an experimental reference for clinical medication.

参考文献

[1] RUSSO T, FELZANI G, MARINI C. Stroke in the very old: A systematic review of studies on incidence, outcome, and resource use[J]. J Aging Res, 2011, 2011: 108785
[2] AHMED N, LEES KR, RINGLEB PA, et al. Outcome after stroke thrombolysis in patients>80 years treated within 3 hours vs>3-4. 5 hours[J]. Neurology, 2017, 89(15): 1561
[3] WANG Y, REN QY, ZHANG X, et al. Neuroprotective mechanisms of calycosin against focal cerebral ischemia and reperfusion injury in rats[J]. Cell Physiol Biochem, 2018, 45(2): 537
[4] LIU P, ZHAO HP, WANG RL, et al. MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress[J]. Stroke, 2015, 46(2): 513
[5] ZHANG N, ZHANG XJ, LIU XX, et al. Chrysophanol inhibits NALP3 inflammasome activation and ameliorates cerebral ischemia/ reperfusion in mice[J]. MediatInflamm, 2014, 2014: 370530
[6] ABU-AMARA M, YANG SY, QUAGLIA A, et al. Role of endothelial nitric oxide synthase in remote ischemic preconditioning of the mouse liver[J]. Liver Transpl, 2011, 17(5): 610
[7] CHEN SD, YANG DI, LIN TK, et al. Roles of oxidative stress, apoptosis, PGC-1 alpha and mitochondrial biogenesis in cerebral ischemia[J]. Int J Mol Sci, 2011, 12(10): 7199
[8] KADIISKA MB, PEDDADA S, HERBERT RA, et al. Biomarkers of oxidative stress study VI. Endogenous plasma antioxidants fail as useful biomarkers of endotoxin-induced oxidative stress[J]. Free Radic Biol Med, 2015, 81: 100
[9] MIAO XL, HUANG Y, PEI J, et al. The Regression analysis on syndromes grade for Yin-yang syndrome differentiation of in acute phase of ischemic stroke[J]. Chin J Integr Trad it West Med, 2007, 5(12): 1166
[10] PEJIN B, JOVANOVIĆ KK, MOJOVIĆ M, et al. New and highly potent antitumor natural products from marine-derived fungi: Covering the period from 2003 to 2012[J]. Curr Top Med Chem, 2013, 13(21): 2745
[11] YU CP, SHIA CS, LIN HJ, et al. Analysis of the pharmacokinetics and metabolism of aloe-emodin following intravenous and oral administrations in rats[J]. Biomed Chromatogr, 2016, 30(10): 1641
[12] ULLAH HMA, KIM J, REHMAN NU, et al. A simple and sensitive liquid chromatography with tandem mass spectrometric method for the simultaneous determination of anthraquinone aglycones and their aglycones in rat plasma: application to a pharmacokinetic study of Rumexacetosa extract[J]. Pharmaceutics, 2018, 10: 100
[13] SUN H, LUO GW, XIANG Z, et al. Pharmacokinetics and pharmacodynamics study of rhein treating renal fibrosis based on metabonomics approach[J]. Phyto Med, 2016, 23(13): 1661
[14] SUN H, YIN QW, ZHANG AH, et al. UPLC-MS/MS performing pharmacokinetic and biodistribution studies of rhein[J]. J Sep Sci, 2012, 35(16): 2063
[15] SHIA CS, HOU YC, TSAI SY, et al. Differences in pharmacokinetics and ex vivo antioxidant activity following intravenous and oral administrations of emodin to rats[J]. J Pharm Sci, 2010, 99(4): 2185
[16] LI RR, LIU XF, FENG SX, et al. Pharmacodynamics of five anthraquinones(aloe-emodin, emodin, rhein, chysophanol, and physcion)and reciprocal pharmacokinetic interaction in rats with cerebral ischemia[J]. Molecules, 2019(24): 1898
[17] BIAN HT, HU Q, LIANG XP, et al. Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through increasing PPARγ in hyperglycemic MCAO rats[J]. Exp Neurol, 2015, 265: 22
[18] MATEL N, CAMARA J, MCBRIDE D, et al. Intranasal wnt3a attenuates neuronal apoptosis through Frz1/PIWIL1a/FOXM1 pathway in MCAO rats[J]. J Neurosci, 2018, 38(30): 6787
[19] MCBRIDE DW, ZHANG JH. Precision stroke animal models: the permanent MCAO model should be the primary model, not transient MCAO[J]. Transl Stroke Res, 2017(8): 397
[20] YANG J, YAN H, LI S, et al. Berberine ameliorates mcao induced cerebral ischemia/reperfusion injury via activation of the BDNF-TrkBPI3K/ Akt signaling pathway[J]. Neurochem Res, 2018, 43(3): 702
[21] LIU Y, WANG XJ, XIONG F, et al. Kinetic study of pyrrolizidine alkaloid-derived pyrrole-protein adducts in rats after intragastric administration of Gynura japonica[J]. Acta Pharm Sin(药学学报), 2020, 55(3): 473
[22] DING CX, GENG YJ, LIU JY, et al. Simultaneous determination of verapamil and its metabolite norverapamil in human plasma by liquid chromatography-tandem mass spectrometry[J]. Acta Pharm Sin(药学学报), 2020, 55(3): 506
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