中国中药杂志

2021, v.46(24) 6530-6541

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丹参葛根对药中8种主要成分在大鼠体内的药代动力学研究
Pharmacokinetics of eight active ingredients of Salviae Miltiorrhizae Radix et Rhizoma-Puerariae Lobatae Radix combination in rats

刘小艳;李晓媛;陈旭;黄志芳;刘云华;刘玉红;陈燕;谭正怀;易进海;
LIU Xiao-yan;LI Xiao-yuan;CHEN Xu;HUANG Zhi-fang;LIU Yun-hua;LIU Yu-hong;CHEN Yan;TAN Zheng-huai;YI Jin-hai;Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica, Sichuan Academy of Chinese Medicine Sciences;Southwest Medical University;Chengdu University of Traditional Chinese Medicine;

摘要(Abstract):

该文采用超高效液相色谱-串联质谱(UPLC-MS/MS)测定大鼠血浆中丹参酚酮成分(丹酚酸B、隐丹参酮、丹参酮Ⅱ_A)和葛根黄酮成分(3′-羟基葛根素、葛根素、葛根素-6″-O-木糖苷、3′-甲氧基葛根素、葛根素芹菜糖苷)血药浓度的分析方法,以期从代谢动力学的角度揭示丹参葛根对药配伍的合理性。大鼠灌胃丹参酚酮提取物、葛根黄酮提取物和丹葛酚酮提取物后采集不同时间点血浆,以Eclipse plus C_(18)(2.1 mm×50 mm, 1.8μm)为色谱柱,0.1%甲酸水溶液(A)-0.1%甲酸乙腈溶液(B)为流动相进行梯度洗脱,采用电喷雾离子源以多反应监测模式(MRM)进行正负离子分段检测。结果显示,8种成分在相应范围内具有良好的线性关系,其精密度、准确度、稳定性、基质效应及回收率结果均符合生物样品定量分析要求。与灌胃单方丹参酚酮和葛根黄酮提取物相比,灌胃复方丹葛酚酮提取物后大鼠血浆中葛根黄酮和丹参酮成分AUC及C_(max)均显著增加,提示丹参葛根对药配伍有利于葛根黄酮和丹参酮成分在体内吸收,相关作用机制有待深入研究。
To reveal the rationality of compatibility of Salviae Miltiorrhizae Radix et Rhizoma(SMRR) and Puerariae Lobatae Radix(PLR) from the perspective of pharmacokinetics, this study established a UPLC-MS/MS method for quantitative determination of PLR flavonoids(3′-hydroxy puerarin, puerarin, puerarin 6″-O-xyloside, 3′-methoxy puerarin, puerarin apioside) and salvianolic acids and tanshinones(salvianolic acid B, cryptotanshinone, and tanshinone Ⅱ_A) in plasma of rats. Rats were given SMRR extract, PLR extract, and SMRR-PLR extract by gavage and then plasma was collected at different time. UPLC separation was performed under the following conditions: Eclipse C_(18) column(2.1 mm×50 mm, 1.8 μm), 0.1% formic acid in water(A)-0.1% formic acid in acetonitrile(B) as mobile phase for gradient elution. Conditions for MS are as below: multiple reaction monitoring(MRM), ESI~(+/-). Comprehensive validation of the UPLC-MS/MS method(specifically, from the aspects of calibration curve, precision, accuracy, repeatability, stability, matrix effect, extract recovery) was performed and the result demonstrated that it complied with quantitative analysis requirements for biological samples. Compared with SMRR extract alone or PLR extract alone, SMRR-PLR extract significantly increased the AUC and C_(max) of PLR flavonoids and tanshinones in rat plasma, suggesting that the combination of SMRR and PLR promoted the absorption of the above components. The underlying mechanism needs to be further studied.

关键词(KeyWords): 丹参;葛根;丹葛酚酮提取物;药代动力学;大鼠
Salviae Miltiorrhizae Radix et Rhizoma;Puerariae Lobatae Radix;Dan′ge Fentong Extract;pharmacokinetics;rat

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2018ZX09731-010,2018ZX09201018-029);; 省级科研院所科技成果转化项目(2019JDZH0034);; 天府万人计划项目(WRJH2019-YJH);; 四川省中央引导地方科技发展专项(2020ZYD039);; 四川省重点研发项目(2021YFS0042)

作者(Author): 刘小艳;李晓媛;陈旭;黄志芳;刘云华;刘玉红;陈燕;谭正怀;易进海;
LIU Xiao-yan;LI Xiao-yuan;CHEN Xu;HUANG Zhi-fang;LIU Yun-hua;LIU Yu-hong;CHEN Yan;TAN Zheng-huai;YI Jin-hai;Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica, Sichuan Academy of Chinese Medicine Sciences;Southwest Medical University;Chengdu University of Traditional Chinese Medicine;

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