Difference Analysis of Pharmacokinetic Behavior of Active Ingredients in Wujiwan Between Normal Rats and Rats with Irritable Bowel Syndrome

Hong ZHANG; Ying CHEN; Zi-peng GONG; Yu DONG; Zi-yu YANG; Qing YANG; Yu-jie LI; Wei-yan CAI; Xiao-gang WENG; Ya-jie WANG; Qi LI; Yuan-long ZANG; Xiao-xin ZHU

doi:10.13422/j.cnki.syfjx.20211048

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Difference Analysis of Pharmacokinetic Behavior of Active Ingredients in Wujiwan Between Normal Rats and Rats with Irritable Bowel Syndrome

Drug Metabolism | 更新时间：2021-07-28

- Difference Analysis of Pharmacokinetic Behavior of Active Ingredients in Wujiwan Between Normal Rats and Rats with Irritable Bowel Syndrome
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 17, Pages: 124-131(2021)
- 作者机构：
  
  1.安徽中医药大学，合肥 230038
  2.中国中医科学院中药研究所，北京 100700
  3.贵州医科大学贵州省药物制剂重点实验室，省部共建药用植物功效与利用国家重点实验室，民族药与中药开发应用教育部工程研究中心，药学院，贵阳 550004
  4.中国中医科学院广安门医院，北京 100053
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211048
  CLC： R22;R969.1;R28;O657
- Received：25 December 2020，
  
  Published Online：26 February 2021，
  
  Published：05 September 2021
- 稿件说明：
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张红,陈颖,巩仔鹏等.戊己丸中活性成分在正常大鼠和肠易激综合征大鼠体内药代动力学行为的差异性分析[J].中国实验方剂学杂志,2021,27(17):124-131.

ZHANG Hong,CHEN Ying,GONG Zi-peng,et al.Difference Analysis of Pharmacokinetic Behavior of Active Ingredients in Wujiwan Between Normal Rats and Rats with Irritable Bowel Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(17):124-131.
张红,陈颖,巩仔鹏等.戊己丸中活性成分在正常大鼠和肠易激综合征大鼠体内药代动力学行为的差异性分析[J].中国实验方剂学杂志,2021,27(17):124-131. DOI： 10.13422/j.cnki.syfjx.20211048.

ZHANG Hong,CHEN Ying,GONG Zi-peng,et al.Difference Analysis of Pharmacokinetic Behavior of Active Ingredients in Wujiwan Between Normal Rats and Rats with Irritable Bowel Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(17):124-131. DOI： 10.13422/j.cnki.syfjx.20211048.

摘要

目的

建立超高效液相色谱-串联质谱法（UPLC-MS/MS）测定戊己丸中10个活性成分口服给药后不同时间点的血药浓度，比较其在正常大鼠和慢性内脏高敏感肠易激综合征（CVH-IBS）大鼠体内药代动力学特征的差异。

方法

采用乳鼠结肠经皮冠状动脉腔内血管成形术（PTCA）球囊刺激法制备CVH-IBS大鼠模型，灌胃给予戊己丸（给药剂量0.245 g·kg

-1

）后于不同时间点从颈静脉采血，采用UPLC-MS/MS同时检测血浆中10个戊己丸活性成分（盐酸小檗碱、盐酸巴马汀、盐酸黄连碱、盐酸药根碱、表小檗碱、二氢小檗碱、吴茱萸碱、吴茱萸内酯、芍药苷、芍药内酯苷）的血药浓度，计算各成分在正常大鼠和CVH-IBS大鼠体内药代动力学参数的差异。

结果

建立的UPLC-MS/MS能够灵敏、准确地检测10个戊己丸活性成分在大鼠体内的血药浓度。与正常组比较，CVH-IBS大鼠体内10个戊己丸活性成分的吸收速率均有一定程度的降低，达峰时间（

max

）延长，其中盐酸小檗碱和盐酸药根碱的

max

分别从54 min和39 min均显著延长至90 min（

0.05，

0.01）；各成分的药-时曲线下面积（AUC

）均增加，其中吴茱萸碱和芍药苷差异有统计学意义（

0.05，

0.01）；10个活性成分的清除率（CL/

）均降低，其中盐酸小檗碱、盐酸巴马汀和吴茱萸碱差异有统计学意义（

0.05，

0.01）。

结论

戊己丸中活性成分在正常大鼠和CVH-IBS大鼠体内的药代动力学行为存在明显差异，这可能与IBS病理状态下肠道上皮细胞的微结构被破坏和肝脏酶的活性改变有关。

Abstract

Objective

To establish an ultra-performance liquid chromatography-mass spectrometry （UPLC-MS/MS） for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration， and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome （CVH-IBS）.

Method

CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty （PTCA） balloon stimulation method. After intragastric administration of Wujiwan （0.245 g·kg

-1

）， blood was collected from the jugular vein at different time points， and the plasma concentrations of 10 active ingredients （berberine hydrochloride， palmatine hydrochloride， coptisine hydrochloride， jatrorrhizine hydrochloride， epiberberine， dihydroberberine， evodiamine， evodine， paeoniflorin， albiflorin） in Wujiwan was detected simultaneously by UPLC-MS/MS， the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated.

Result

The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group， the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent， and the peak time （

max

） was prolonged. Among them， the

max

of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute， respectively （

0.05，

0.01）. Area under the plasma concentration-time curve （AUC

） of each component increased， and evodiamine and paeoniflorin were significantly different （

0.05，

0.01）. The clearance rates （CL/

） of these 10 active ingredients were all decreased， among which berberine hydrochloride， palmatine hydrochloride and evodiamine had significant differences （

0.05，

0.01）.

Conclusion

There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats， which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.

关键词

Keywords

references

李夏，王凤云，吴皓萌，等 . 基于脑-肠互动功能探讨痛泻要方治疗腹泻性肠易激综合征机制的研究进展［J］. 中国实验方剂学杂志， 2020 ， 26 （ 20 ）： 229 - 234 .

UDAY C G . Marshall and Warren Lecture 2019：a paradigm shift in pathophysiological basis of irritable bowel syndrome and its implication on treatment ［J］. J Gastroen Hepatol ， 2020 ， 35 （ 5 ）： 712 - 721 .

赵艳钧，杨勤 . 肠易激综合征内脏高敏感的调控机制研究进展［J］. 现代消化及介入诊疗， 2020 ， 25 （ 3 ）： 407 - 410 .

MOAYYEDI P ， SIMREN M ， BERCIK P . Evidence-based and mechanistic insights into exclusion diets for IBS ［J］. Nat Rev Gastro Hepat ， 2020 ， 17 （ 7 ）： 406 - 413 .

郑和平，张智彬，魏先鹏，等 . 逍遥散合四磨汤加减对便秘型肠易激综合征肝郁气滞证脑-肠轴的影响［J］. 中国实验方剂学杂志， 2020 ， 26 （ 22 ）： 53 - 58 .

韦宇，张莉莉，顾成娟 . 黄连、吴茱萸、白芍治疗腹泻型肠易激综合征经验——仝小林三味小方撷萃［J］. 吉林中医药， 2020 ， 40 （ 10 ）： 1270 - 1272 .

宫海民，王兆淦，段文卓 . 戊已丸镇痛、抗炎作用的实验研究［J］. 中国中医药科技， 1998 ， 5 （ 3 ）： 147 - 148 .

国家药典委员会 . 中华人民共和国药典：一部［M］. 北京：化学工业出版社， 2005 ： 416 - 417 .

巩仔鹏 . 基于肠易激综合征模型的戊己丸药代动力学研究［D］. 北京：中国中医科学院， 2014 .

王娅杰，董宇，朱晓新 . 戊己丸提取物不同配伍方对豚鼠离体结肠运动影响的实验研究［J］. 中国中药杂志， 2007 ， 32 （ 20 ）： 2161 - 2165 .

CHEN J Y ， CHEN Z ， MA L ， et al . Development of determination of four analytes of Zhi-Shao-San decoction using LC-MS/MS and its application to comparative pharmacokinetics in normal and irritable bowel syndrome rat plasma ［J］. Biomed Chromatogr ， 2014 ， 28 （ 10 ）： 1384 - 1392 .

HOU Q K ， ZHU S L ， ZHANG C R ， et al . Berberine improves intestinal epithelial tight junctions by upregulating A20 expression in IBS-D mice ［J］. Biomed Pharmacother ， 2019 ， 118 ： 109206 .

ZHANG C R ， HUANG Y Q ， LI P W ， et al . Ginger relieves intestinal hypersensitivity of diarrhea predominant irritable bowel syndrome by inhibiting proinflammatory reaction ［J］. BMC Complem Altern M ， 2020 ， 20 （ 1 ）： 279 .

何力，杨力，凌志维，等 . 基于脑肠交互机制探讨肠道微生物调节IBS-D内脏高敏的研究进展［J］. 中国实验方剂学杂志， 2019 ， 25 （ 11 ）： 224 - 229 .

SCALDAFERRI F ， PIZZOFERRATO M ， GERARDI V ， et al . The gut barrier：new acquisitions and therapeutic approaches ［J］. J Clin Gastroenterol ， 2012 ， 46 （ Suppl ）： S12 - S17 .

DARKOH C ， COMER L ， ZEWDIE G ， et al . Chemotactic chemokines are important in the pathogenesis of irritable bowel syndrome ［J］. PLoS One ， 2014 ， 9 （ 3 ）： e93144 .

GONG Z P ， CHEN Y ， ZHANG R J ， et al . Pharmacokinetic difference of berberine between normal and chronic visceral hypersensitivity irritable bowel syndrome rats and its mechanism ［J］. Arch Pharm Res ， 2015 ， 38 （ 10 ）： 1888 - 1896 .

李备，刘华蓉，潘永全，等 . 黄连总生物碱对乙醇致大鼠胃黏膜损伤的保护作用及其机制探讨［J］. 中国中药杂志， 2006 ， 31 （ 1 ）： 51 - 54 .

MA B L ， YAO M K ， ZHONG J ， et al . Increased systemic exposure to rhizoma coptidis alkaloids in lipopolysaccharide-pretreated rats attributable to enhanced intestinal absorption ［J］. Drug Metab Dispos ， 2012 ， 40 （ 2 ）： 381 - 388 .

蔡扬 . 黄连吴茱萸配伍对实验性功能性消化不良大鼠胃排空及胃肠激素的影响［D］. 成都：成都中医药大学， 2013 .

严子玲，于洋，何金莲，等 . 五味子配伍对吴茱萸主成分肠吸收的影响及可能机制研究［J］. 江西中医药， 2013 ， 44 （ 9 ）： 59 - 62 .

蔡翠珠，黄少君，刘海涛 . 治胃汤治疗胆汁反流性胃炎（肝胃不和型）的临床疗效及对血浆胃动素的影响［J］. 世界中西医结合杂志， 2020 ， 15 （ 10 ）： 1765 - 1768，1818 .

YUAN J ， WANG Y ， AN R ， et al . Simultaneous determination of six alkaloids and one monoterpene in rat plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetic study after oral administration of a Chinese medicine Wuji pill ［J］. J Chromatogr B ， 2012 ， 895/896 ： 154 - 161 .

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