杜仲盐炙前后主要活性成分在肾纤维化大鼠体内的药代动力学研究  

Pharmacokinetic investigation of principal active constituents in renal fibrotic rats after oral administration of crude and salt-processed eucommiae cortex extracts

作　　者：王梦晴 蔡皓[1,2] 刘鑫 宋健涛 曹岗[3] 朱慧[1,2] 段煜[1,2] 裴科[4] WANG Meng-qing;CAI Hao;LIU Xin;SONG Jian-tao;CAO Gang;ZHU Hui;DUAN Yu;PEI Ke(School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing,Nanjing University of Chinese Medicine,Nanjing 210023,China;School of Pharmacy,Zhejiang Chinese Medical University,Hangzhou 310053,China;School of Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 030619,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]南京中医药大学国家教育部中药炮制规范化及标准化工程研究中心,江苏南京210023 [3]浙江中医药大学药学院,浙江杭州310053 [4]山西中医药大学中药与食品工程学院,山西晋中030619

出　　处：《药学学报》2023年第6期1611-1618,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金优秀青年基金项目(81922073)。

摘　　要：建立杜仲生、盐炙品提取物中6种主要活性成分(桃叶珊瑚苷、绿原酸、京尼平苷酸、松脂醇二葡萄糖苷、京尼平苷和松脂醇单葡萄糖苷)在腺嘌呤致肾纤维化模型大鼠血浆中的定量分析方法,并对比研究其体内药代动力学行为。应用UHPLC-Qq Q-MS/MS技术,采用负离子模式进行扫描,以MRM配对离子方式进行定量,同时对其专属性、线性范围、准确度、精密度、稳定性、提取回收率及基质效应进行考察,方法学考察结果均符合生物样本的分析要求。成功建立了一种可同时测定杜仲生、盐炙品提取物中6种活性成分在大鼠血浆中快速、灵敏、准确的定量分析方法,并对肾纤维化大鼠单次给予杜仲生、盐炙品提取物后不同时间点各成分的血药浓度进行检测,计算各成分的药代动力学参数并构建药-时曲线。本实验获得南京中医药大学实验动物伦理委员会批准(批准号:202103A008)。结果表明,与杜仲生品组相比,杜仲盐炙品组大鼠血浆中桃叶珊瑚苷、松脂醇二葡萄糖苷、京尼平苷和松脂醇单葡萄糖苷等化合物的tmax值均显著小于生品组(P<0.05,P<0.01);绿原酸的Cmax、AUC0-48 h,松脂醇二葡萄糖苷的Cmax、AUC0-48 h和AUC0-∞,京尼平苷以及松脂醇单葡萄糖苷的Cmax均显著高于生品组(P<0.05,P<0.01)。研究发现,相较于杜仲生品,多种活性成分在杜仲盐炙品的给药环境下可发挥速效作用,有更高的血药浓度峰值与生物利用度,进一步验证了“入盐走肾脏”的中医理论,为杜仲生品及其盐炙品质控指标的选择、炮制机制的阐明和体内代谢规律的深入研究提供了实验参考依据。A quantitative analysis method for six principal active constituents(acubin,geniposidic acid,chlorogenic acid,pinoresinol di-O-glucopyranoside,geniposide,and pinoresinol 4-O-glucopyranoside)of crude Eucommiae Cortex(EC)and its salt-processed product extracts was developed to investigate and compare their pharmacokinetic behaviors in adenine-induced renal fibrotic rats in vivo.UHPLC-QqQ-MS/MS technology was employed.Scan was conducted in negative ion mode and quantitative determination was carried out by MRM paired ion.The established method was fully validated by specificity,linearity,precision,accuracy,stability,recovery,and matrix effect,and the results of methodological investigation met the requirements of biological sample analysis.Then,a quick,sensitive,and accurate method was successfully established,which could simultaneously measure the contents of six active constituents of crude and salt-processed EC extracts in rat plasma.After a single administration to renal fibrotic rats of crude EC and its salt-processed product extracts,the plasma concentration of each constituent at different time points was measured,the pharmacokinetic parameters were calculated and the concentration time curves were structured.The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine(No.202103A008).The results showed that compared to the crude Eucommiae Cortex group,the tmax of aucubin,pinoresinol di-O-glucopyranoside,geniposide,and pinoresinol 4-O-glucopyranoside in the salt-processed Eucommiae Cortex group rat plasma were significantly lower than those in the crude group(P<0.05,P<0.01);the Cmax and AUC0-48 h of chlorogenic acid,the Cmax,AUC0-48 h and AUC0-∞of pinoresinol di-O-glucopyranoside,and the Cmax of geniposide and pinoresinol 4-O-glucopyranoside were significantly higher than those in the crude group(P<0.05,P<0.01).Our investigation found that compared to crude Eucommiae Cortex,a variety of active ingredients could play a role of quick effect with higher pea

关 键 词：杜仲 盐炙 肾纤维化 药代动力学 UHPLC-QqQ-MS/MS 

分 类 号：R917[医药卫生—药物分析学]