杜仲提取物多次给药后在正常大鼠和 SHR 模型体内的药动学比较研究
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1.贵州医科大学贵州省药物制剂重点实验室 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; 2.中国中医科学院中药研究所,北京 100700

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R-33


Pharmacokinetic comparison of active components in an Eucommia ulmoides extract by multiple administrations between normal and spontaneously hypertensive rats
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1.Guizhou Medical University Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, School of Pharmacy, Guiyang 550004, China. 2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700

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    摘要:

    目的 研究杜仲提取物多次给药后松脂醇二葡萄糖苷(( +)-pinoresinol di-O-β-D-glucopyr-anoside, PDG)、京尼平苷酸(genipinic acid,GA)、绿原酸(chlorogenic acid,CA)、原儿茶酸(protocatechuic acid,PCA)、新绿原酸(neochlorogenicacid,NCA)、隐绿原酸(cryptochlorogenic acid,CCA)和松脂醇单葡萄糖苷((+)-pinoresinol 4’-O-β- D-glucopyrano-side,PG)7 个活性成分在正常大鼠和自发性高血压大鼠机体内的药代动力学差异。 方法 采用正常大鼠和自发性高血压大鼠为实验对象,以 5. 4 g / kg 的给药剂量灌胃杜仲提取物,每天 1 次,连续 7 d,比较杜仲提取物中的 7 个活性成分在正常大鼠与 SHR 模型体内的药代动力学和组织蓄积情况差异。 结果 药代动力学的研究结果发现,CCA 和 NCA 在 SHR 模型体内的药动学参数与正常组比较无明显差异。在 SHR 模型组体内 PDG 的 t1/ 2 为正常组的 0.26 倍;GA 的 t1/ 2 、tmax、AUC0-t在 SHR 模型组中分别为正常组的 2. 20、0. 04、0. 50 倍;PG 在 SHR 模型组体内的 t1/ 2为正常组的 0. 55 倍;PCA 在 SHR 模型组内的 t1/ 2为正常组的 2. 04 倍;CA 的 t1/ 2 、AUC0-t分别为正常组的 1. 93、0. 64 倍。 蓄积实验结果发现,GA 等 7 种活性成分主要分布在胃、小肠、心、肝和肺中。 除 CCA 外,CA、 NCA、PCA、GA、PDG 和 PG 在 SHR 模型体内与正常组相比,含量存在显著差异的组织器官数量分别为 2 ~ 7 个不等。 结论 自发性高血压病理状态下的机体能够显著改变杜仲降压活性成分在血浆中药动学行为以及组织中的蓄积情况,而对于需要长期服药的高血压患者而言,药物在体内的药动学行为尤为重要,本研究可为杜仲在临床上的长期使用剂量调整提供一定的参考。

    Abstract:

    Objective To investigate differences in pharmacokinetics and accumulation of seven bioactive constituents, namely (+)-pinoresinol di-O-β-D-glucopyr-anoside (PDG), genipinic acid (GA), chlorogenic acid (CA), protocatechuic acid (PCA), neochlorogenic acid (NCA), cryptochlorogenic acid (CCA) and (+)-pinoresinol 4’-O-β-D- glucopyrano-side ( PG) in Eucommia ulmoides after multiple intragastric administrations between normal rats and spontaneously hypertensive rats ( SHRs). Methods Normal rats and SHRs received intragastric Eucommia ulmoides extract at a dose of 5.4 g / ( kg·d) for 7 consecutive days. Then, the pharmacokinetic parameters and tissue distribution were compared between normal rats and SHRs. Results Pharmacokinetic tests showed no obvious differences in all pharmacokinetic parameters of NCA and CCA between normal and model groups. The t1/ 2 value of PDG in SHRs was 0.26 times that of normal rats. In model group, the t1/ 2 , tmax and AUC0-t of GA were 2.20, 0.04 and 0.50 times those of normal group, respectively. For model group, the t1/ 2 value of PG was 0.55 times that of normal group. Compared with normal rats, the t1/ 2 of PCA in SHRs was increased by 2.04 times. The t1/ 2 and AUC0-t of CA in SHRs were 1.93 and 0.64 times of normal rats, respectively. Accumulation analysis showed that all representative active components were mainly distributed in the stomach, intestines, heart, liver and lungs. Except for CCA, the contents of the others in SHRs presented notable differences in tissues of two to seven compared with normal group. Conclusions The pharmacokinetics and accumulation of active anti-hypertensive components in Eucommia ulmoides extract after multiple administrations in rats were influenced remarkably by the pathological state of spontaneous hypertension. Moreover, it is important to learn about the pharmacokinetic characteristics of drugs for those who suffer from hypertension and need to take medicine persistently. This study provides a reference for clinical dosage adjustment of Eucommia ulmoides when used long-term.

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张 青,李梦婷,李 梅,鲍红松,黄 勇,郑 林,李月婷,陈颖,巩仔鹏.杜仲提取物多次给药后在正常大鼠和 SHR 模型体内的药动学比较研究[J].中国比较医学杂志,2022,32(1):41~47.

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  • 收稿日期:2021-10-28
  • 在线发布日期: 2022-03-15
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