牡丹皮药效组分的整合药代动力学考察及其与药效的相关性分析
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摘要
目的:研究牡丹皮中5个药效成分(氧化芍药苷、芍药苷、槲皮素、没食子酸、丹皮酚)的整合药代动力学及其与药效作用之间的相关性。方法:将大鼠分为空白组、模型组(血热瘀血证)和给药组,采用UPLC-MS测定大鼠给药后不同时间点血清中5个药效成分的血药浓度,根据自定义权重系数计算得到相应的整合血药浓度。采用酶联免疫吸附测定法(ELISA)测定不同时间点血清中血栓素B2(TXB2)和6-酮-前列腺素F1α(6-keto-PGF1α)的质量浓度,并考察整合药代动力学与药效之间的相关性。结果:牡丹皮中5个药效成分在不同时间点(0. 083,0. 25,0. 5,0. 75,1,2,3,4,6,8,10,12 h)的整合血药浓度(158. 65,174. 60,220. 13,227. 23,244. 31,251. 51,404. 28,654. 39,472. 62,355. 04,231. 56,199. 40 mg·L-1)与TXB2质量浓度(264. 44,261. 03,284. 93,273. 30,264. 04,278. 90,274. 83,303. 58,260. 03,264. 78,264. 40,256. 62μg·L-1)和TXB2/6-ketoPGF1α(4. 50,4. 47,3. 66,3. 37,3. 29,3. 66,3. 71,4. 30,3. 63,3. 65,3. 75,3. 66)的相关性良好。结论:牡丹皮药效组分在体内的动态变化与活血药效之间存在良好的相关性。
Objective: To study on the correlation between integrated pharmacokinetics and pharmacodynamic effects of five active components(oxidized paeoniflorin,paeoniflorin,quercetin,gallic acid,paeonol) in Moutan Cortex. Method: Rats were divided into blank group,model group(syndrome of blood-heat and blood stasis) and drug-administered group. The concentration of five active components in serum were detected with UPLC-MS at different time points after being administrated ethanol extract of Moutan Cortex. The integrated concentrations were calculated according to area under the curve(AUC) self-defined weighting coefficiency. At the same time, the enzyme-linked immunosorbent assay(ELISA) was used to determine the contents of thromboxane B2(TXB2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) in serum at different time points,and then correlation between pharmacodynamics and integrated pharmacokinetics of these five active ingredients was analyzed. Result: At different time points(0. 083,0. 25,0. 5,0. 75,1,2,3,4,6,8,10,12 h),the integrated plasma concentrations of these five active ingredients in Moutan Cortex(158. 65,174. 60,220. 13,227. 23,244. 31,251. 51,404. 28,654. 39,472. 62,355. 04,231. 56,199. 40 mg · L-1) had a good correlation with concentration of TXB2(264. 44,261. 03,284. 93,273. 30,264. 04,278. 90,274. 83,303. 58,260. 03,264. 78,264. 40,256. 62 μg·L-1) and value of TXB2/6-keto-PGFlα(4. 50,4. 47,3. 66,3. 37,3. 29, 3. 66, 3. 71, 4. 30, 3. 63, 3. 65, 3. 75, 3. 66). Conclusion: There is a good correlation between the dynamic changes in vivo of active components from Moutan Cortex and pharmacodynamic effects of activating blood circulation of this herb.
Objective: To study on the correlation between integrated pharmacokinetics and pharmacodynamic effects of five active components(oxidized paeoniflorin,paeoniflorin,quercetin,gallic acid,paeonol) in Moutan Cortex. Method: Rats were divided into blank group,model group(syndrome of blood-heat and blood stasis) and drug-administered group. The concentration of five active components in serum were detected with UPLC-MS at different time points after being administrated ethanol extract of Moutan Cortex. The integrated concentrations were calculated according to area under the curve(AUC) self-defined weighting coefficiency. At the same time, the enzyme-linked immunosorbent assay(ELISA) was used to determine the contents of thromboxane B2(TXB2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) in serum at different time points,and then correlation between pharmacodynamics and integrated pharmacokinetics of these five active ingredients was analyzed. Result: At different time points(0. 083,0. 25,0. 5,0. 75,1,2,3,4,6,8,10,12 h),the integrated plasma concentrations of these five active ingredients in Moutan Cortex(158. 65,174. 60,220. 13,227. 23,244. 31,251. 51,404. 28,654. 39,472. 62,355. 04,231. 56,199. 40 mg · L-1) had a good correlation with concentration of TXB2(264. 44,261. 03,284. 93,273. 30,264. 04,278. 90,274. 83,303. 58,260. 03,264. 78,264. 40,256. 62 μg·L-1) and value of TXB2/6-keto-PGFlα(4. 50,4. 47,3. 66,3. 37,3. 29, 3. 66, 3. 71, 4. 30, 3. 63, 3. 65, 3. 75, 3. 66). Conclusion: There is a good correlation between the dynamic changes in vivo of active components from Moutan Cortex and pharmacodynamic effects of activating blood circulation of this herb.
引文
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[6]王瑛兰,李凌军,张微.天钩降压胶囊中丹皮酚在大鼠体内药代动力学[J].中国实验方剂学杂志,2012,18(3):114-116.
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[8]李燕,彦培傲,赵梦杰,等.附子总生物碱在阳虚便秘模型大鼠体内的整合药动学分析[J].中国实验方剂学杂志,2017,23(1):79-84.
[9]郝海平,郑超湳,王广基.多组分、多靶点中药整体药代动力学研究的思考与探索[J].药学学报,2009,44(3):270-275.
[10]陶野,张贝贝,付梅红,等.基于色谱指纹图谱的苍术挥发油多成分体内药代动力学研究[J].中国实验方剂学杂志,2013,19(11):156-159.
[11]张启云,徐良辉,李冰涛,等.复方葛根答连汤多效应成分分类整合药代动力学研究[J].中国临床药理学与治疗学,2011,16(1):51-56.
[12]王静,陈悦,袁子民.胆黄连在实热证大鼠体内的整合药代动力学与药效学的相关性[J].药学学报,2016,51(1):127-131.
[13]巩仔鹏,胡建春,李梅,等.基于大鼠脑缺血再灌注损伤模型建立辛芍组方中灯盏乙素和芍药苷的PK-PD结合模型[J].中国实验方剂学杂志,2018,24(1):74-78.
[14]郭娟,陈长勋,沈云辉.葶苈子水提液对动物实验性心室重构的影响[J].中草药,2007,38(10):1519-1523.
[2]李方军.牡丹皮化学成分及药理作用研究进展[J].安徽医药,2004,8(1):9-10.
[3]郭齐,李连达,郝伟,等.牡丹皮有效组分重组方对家兔血小板聚集及凝血功能的影响[J].中国现代应用药学,2010,27(11):967-970.
[4]王乃利,倪艳,陈英杰,等.广枣活血有效成分的研究[J].沈阳药学院学报,1987,4(3):2-3.
[5]王艳芳,王新华,朱宇同.槲皮素药理作用研究进展[J].天然产物研究与开发,2003,15(2):171-173.
[6]王瑛兰,李凌军,张微.天钩降压胶囊中丹皮酚在大鼠体内药代动力学[J].中国实验方剂学杂志,2012,18(3):114-116.
[7]吴豪.中药牡丹皮质量控制及其有效成分的药代动力学研究[D].上海:第二军医大学,2009.
[8]李燕,彦培傲,赵梦杰,等.附子总生物碱在阳虚便秘模型大鼠体内的整合药动学分析[J].中国实验方剂学杂志,2017,23(1):79-84.
[9]郝海平,郑超湳,王广基.多组分、多靶点中药整体药代动力学研究的思考与探索[J].药学学报,2009,44(3):270-275.
[10]陶野,张贝贝,付梅红,等.基于色谱指纹图谱的苍术挥发油多成分体内药代动力学研究[J].中国实验方剂学杂志,2013,19(11):156-159.
[11]张启云,徐良辉,李冰涛,等.复方葛根答连汤多效应成分分类整合药代动力学研究[J].中国临床药理学与治疗学,2011,16(1):51-56.
[12]王静,陈悦,袁子民.胆黄连在实热证大鼠体内的整合药代动力学与药效学的相关性[J].药学学报,2016,51(1):127-131.
[13]巩仔鹏,胡建春,李梅,等.基于大鼠脑缺血再灌注损伤模型建立辛芍组方中灯盏乙素和芍药苷的PK-PD结合模型[J].中国实验方剂学杂志,2018,24(1):74-78.
[14]郭娟,陈长勋,沈云辉.葶苈子水提液对动物实验性心室重构的影响[J].中草药,2007,38(10):1519-1523.
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