辛芍组方中5个指标成分在大鼠体内的组织分布情况
|
摘要
目的:研究大鼠灌胃辛芍组方后其5个指标成分在体内的组织分布情况。方法:建立同时测定大鼠组织中灯盏甲素、灯盏乙素、灯盏乙素苷元、芍药苷、芍药内酯苷的UPLC-MS/MS,将辛芍组方灌胃给予SD大鼠(剂量25 g·kg~(-1)),分别于给药后20,90 min和12,24 h取其主要脏器和组织,采用UPLC-MS/MS测定各个时间点下5个指标成分在脏器和组织中的分布情况。结果:大鼠灌胃辛芍组方后,5个指标成分可广泛分布于大鼠各组织器官中。对于灯盏甲素,其质量浓度20 min时在肺和心中达到峰值,分别为48.2,59.8μg·L~(-1);90 min时在脑和小肠中达到峰值,分别为138.7,292.7μg·L~(-1);12 h时在肾和肌肉中达到峰值,为517.3,56.5μg·L~(-1);24 h时在肝脏中达到峰值,为352.9μg·L~(-1)。对于灯盏乙素,其质量浓度20 min时在心中达到峰值,为38.3μg·L~(-1);90 min时在肺、脑、小肠和肾中达到峰值,分别为30.6,220.0,1 644.2,859.9μg·L~(-1);12 h时在肌肉中达到峰值,为86.9μg·L~(-1);24 h时在肝脏中达到峰值,为344.8μg·L~(-1)。对于灯盏乙素苷元,其质量浓度90 min时在脑、小肠和肌肉中达到峰值,分别为875.4,52 468.0,5 114.7μg·L~(-1);12 h时在肺、心和肾中达到峰值,分别为609.7,1 718.6,1 736.5μg·L~(-1);24 h时在肝脏中达到峰值,为1 366.5μg·L~(-1)。对于芍药苷,其质量浓度20 min时在肺、肝、肾和肌肉中达到峰值,分别为10 634.1,13 889.0,16 672.0,7 750.4μg·L~(-1);在90 min时,在心、小肠和脑中达到峰值,分别为6 851.1,870 563.9,7 474.0μg·L~(-1)。对于芍药内酯苷,其质量浓度20 min时在肝和肾中达到峰值,分别为15 249.7,56 817.0μg·L~(-1),在90 min时,在肺、心、脑、小肠和肌肉中达到峰值,分别为4 211.5,4 425.3,4 631.3,631 871.5,5 673.6μg·L~(-1)。结论:大鼠灌胃辛芍组方后,5个指标成分可迅速、广泛地分布在各组织器官中,但5个指标成分在各组织脏器中的达峰时间和分布存在一定差异,在肾脏和小肠中的分布最高,其次为肝和肌肉,同时在脑组织中也有分布,并且随着给药时间的延长,灯盏甲素、灯盏乙素和灯盏乙素苷元可能在大鼠的肝脏中会发生蓄积。
Objective: To study on the tissue distribution of five components from Xinshao formula in rats after administered intragastrically. Method: UPLC-MS/MS for the simultaneous determination of apigenin-7-Oglucronide,scutellarin,scutellarin aglycone,paeoniflorin and albiflorin in rat tissues was established. Rats were administered intragastrically Xinshao formula at a dose of 25 g·kg~(-1),and main tissues and organs were collected from rats at 20,90 min and 12,24 h after administration. After pretreatment,the concentrations of apigenin-7-Oglucronide,scutellarin,scutellarin aglycone,paeoniflorin and albiflorin in each organ of each time point were determined. Result: After being administered Xinshao formula,five components could be widely distributed in tissues and organs of rats. For apigenin-7-O-glucronide,its concentration peaked in the lung and heart at 20 min with 48. 2,59. 8 μg·L~(-1); peaked in the brain and small intestine at 90 min with 138. 7,292. 7 μg·L~(-1); peaked in kidney and muscle at 12 h with 517. 3,56. 5 μg·L~(-1); peaked in the liver at 24 h with 352. 9 μg·L~(-1). For scutellarin,its concentration peaked in the heart at 20 min with 38. 3 μg·L~(-1); peaked in the lung,brain,small intestine and kidney at 90 min with 30. 6,220. 0,1 644. 2,859. 5 μg·L~(-1); peaked in the muscle at 12 h with86. 9 μg·L~(-1) and in the liver at 24 h with 344. 8 μg·L~(-1). For scutellarin aglycone,its concentration peaked in the brain,small intestine and muscle at 90 min with 875. 4,52 468. 0,5 114. 7 μg·L~(-1); peaked in lung,heart and kidney at 12 h with 609. 7,1 718. 6,1 736. 5 μg·L~(-1) and peaked in the liver at 24 h with 1 366. 5 μg·L~(-1).For paeoniflorin,its concentration reached peaks in the lung,liver,kidney and muscle at 20 min with 10 634. 1,13 889. 0,16 672. 0,7 750. 4 μg·L~(-1); and reached in the heart,small intestine and brain at 90 min with6 851. 1,870 563. 9,7 474. 0 μg·L~(-1). For albiflorin,its concentration peaked in the liver and kidney at 20 min with 15 249. 7,56 817. 0 μg·L~(-1); peaked in the lung,heart,brain,small intestine and muscle at 90 min with4 211. 5, 4 425. 3, 4 631. 3, 631 871. 5, 5 673. 6 μg·L~(-1). Conclusion: After the rats administered intragastrically Xinshao formula,its five components could be widely and quickly distributed in various tissues and organs; however,there are differences in the peak time and distribution of these five components. The five representative components have the highest distribution in the kidney and small intestine,followed by the liver and muscle tissues,but also in the brain. Moreover,apigenin-7-O-glucronide,scutellarin,scutellarin aglycone may accumulate in the rat liver when the time of drug administered is extended.
Objective: To study on the tissue distribution of five components from Xinshao formula in rats after administered intragastrically. Method: UPLC-MS/MS for the simultaneous determination of apigenin-7-Oglucronide,scutellarin,scutellarin aglycone,paeoniflorin and albiflorin in rat tissues was established. Rats were administered intragastrically Xinshao formula at a dose of 25 g·kg~(-1),and main tissues and organs were collected from rats at 20,90 min and 12,24 h after administration. After pretreatment,the concentrations of apigenin-7-Oglucronide,scutellarin,scutellarin aglycone,paeoniflorin and albiflorin in each organ of each time point were determined. Result: After being administered Xinshao formula,five components could be widely distributed in tissues and organs of rats. For apigenin-7-O-glucronide,its concentration peaked in the lung and heart at 20 min with 48. 2,59. 8 μg·L~(-1); peaked in the brain and small intestine at 90 min with 138. 7,292. 7 μg·L~(-1); peaked in kidney and muscle at 12 h with 517. 3,56. 5 μg·L~(-1); peaked in the liver at 24 h with 352. 9 μg·L~(-1). For scutellarin,its concentration peaked in the heart at 20 min with 38. 3 μg·L~(-1); peaked in the lung,brain,small intestine and kidney at 90 min with 30. 6,220. 0,1 644. 2,859. 5 μg·L~(-1); peaked in the muscle at 12 h with86. 9 μg·L~(-1) and in the liver at 24 h with 344. 8 μg·L~(-1). For scutellarin aglycone,its concentration peaked in the brain,small intestine and muscle at 90 min with 875. 4,52 468. 0,5 114. 7 μg·L~(-1); peaked in lung,heart and kidney at 12 h with 609. 7,1 718. 6,1 736. 5 μg·L~(-1) and peaked in the liver at 24 h with 1 366. 5 μg·L~(-1).For paeoniflorin,its concentration reached peaks in the lung,liver,kidney and muscle at 20 min with 10 634. 1,13 889. 0,16 672. 0,7 750. 4 μg·L~(-1); and reached in the heart,small intestine and brain at 90 min with6 851. 1,870 563. 9,7 474. 0 μg·L~(-1). For albiflorin,its concentration peaked in the liver and kidney at 20 min with 15 249. 7,56 817. 0 μg·L~(-1); peaked in the lung,heart,brain,small intestine and muscle at 90 min with4 211. 5, 4 425. 3, 4 631. 3, 631 871. 5, 5 673. 6 μg·L~(-1). Conclusion: After the rats administered intragastrically Xinshao formula,its five components could be widely and quickly distributed in various tissues and organs; however,there are differences in the peak time and distribution of these five components. The five representative components have the highest distribution in the kidney and small intestine,followed by the liver and muscle tissues,but also in the brain. Moreover,apigenin-7-O-glucronide,scutellarin,scutellarin aglycone may accumulate in the rat liver when the time of drug administered is extended.
引文
[1]董永喜,王霞,董莉,等.辛芍组方对缺血再灌注损伤后神经细胞氧化应激及NF-κB信号通路的影响[J].山东医药,2016,56(42):5-8.
[2]董永喜,董莉,付思红,等.辛芍组方对氧糖剥夺损伤的神经PC12细胞凋亡的影响及其机制研究[J].中国药房,2016,27(28):3907-3910.
[3]陆苑,张洁,兰燕宇,等.灯盏细辛-赤芍组方配比及给药途径的脑保护作用[J].中国实验方剂学杂志,2013,19(21):175-178.
[4]刘宗炎,董莉,董永喜,等.灯盏细辛与赤芍配伍组方对H2O2致PC12细胞损伤的保护作用[J].中国实验方剂学杂志,2014,20(5):180-183.
[5]王永林,黄勇,兰燕宇,等.注射用辛芍冻干粉针药味配伍作用研究[J].中国实验方剂学杂志,2007,13(7):38-40.
[6]郑林,牟景丽,黄勇,等.UPLC-MS/MS法同时测定注射用辛芍中7种指标成分的含量[J].中国新药杂志,2014,23(1):105-109.
[7]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.
[8]王晓彤,何凡,孙小玲,等.五味子有效成分在大鼠体内组织分布研究[J].中药药理与临床,2017,33(5):20-23.
[9]宋帅,梁德东,任孟月,等.麻黄-杏仁药对有效成分在大鼠体内组织分布的定量分析[J].中国实验方剂学杂志,2016,22(12):92-97.
[10]张宜凡,张艺竹,陈烨,等.葛根芩连汤中黄芩活性成分在大鼠体内的组织分布[J].中国实验方剂学杂志,2013,19(19):177-182.
[2]董永喜,董莉,付思红,等.辛芍组方对氧糖剥夺损伤的神经PC12细胞凋亡的影响及其机制研究[J].中国药房,2016,27(28):3907-3910.
[3]陆苑,张洁,兰燕宇,等.灯盏细辛-赤芍组方配比及给药途径的脑保护作用[J].中国实验方剂学杂志,2013,19(21):175-178.
[4]刘宗炎,董莉,董永喜,等.灯盏细辛与赤芍配伍组方对H2O2致PC12细胞损伤的保护作用[J].中国实验方剂学杂志,2014,20(5):180-183.
[5]王永林,黄勇,兰燕宇,等.注射用辛芍冻干粉针药味配伍作用研究[J].中国实验方剂学杂志,2007,13(7):38-40.
[6]郑林,牟景丽,黄勇,等.UPLC-MS/MS法同时测定注射用辛芍中7种指标成分的含量[J].中国新药杂志,2014,23(1):105-109.
[7]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.
[8]王晓彤,何凡,孙小玲,等.五味子有效成分在大鼠体内组织分布研究[J].中药药理与临床,2017,33(5):20-23.
[9]宋帅,梁德东,任孟月,等.麻黄-杏仁药对有效成分在大鼠体内组织分布的定量分析[J].中国实验方剂学杂志,2016,22(12):92-97.
[10]张宜凡,张艺竹,陈烨,等.葛根芩连汤中黄芩活性成分在大鼠体内的组织分布[J].中国实验方剂学杂志,2013,19(19):177-182.