扶正化瘀方灌胃给药后正常及肝纤维化大鼠体内木脂素成分的比较药代动力学和组织分布特征。
Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.
机构信息
Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
出版信息
J Ethnopharmacol. 2015 May 26;166:305-12. doi: 10.1016/j.jep.2015.03.024. Epub 2015 Mar 18.
ETHNOPHARMACOLOGICAL RELEVANCE
Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis.
AIM OF THE STUDY
To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY.
MATERIALS AND METHODS
Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats.
RESULTS
A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (P<0.05). Tissue distribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (P<0.05). Meanwhile, the result also reveals that the hepatic fibrosis could delay the peak time of lignans in liver.
CONCLUSION
The results proved that the established UHPLC-MS/MS method could be applied to the comparative study on pharmacokinetics and tissue distribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine.
民族药理学相关性
扶正化瘀方（FZHY）是基于中医药理论治疗肝纤维化的方剂。
研究目的
阐明肝纤维化病理状态对 FZHY 中木脂素成分药代动力学和组织分布特征的影响。
材料和方法
雄性 Wistar 大鼠随机分为正常组和肝纤维化组（用二甲基亚硝胺诱导）。采用超高效液相色谱-串联质谱法（UHPLC-MS/MS）检测和定量正常和肝纤维化大鼠血浆和组织中的六种木脂素成分。
结果
成功建立了一种快速、灵敏、方便的 UHPLC-MS/MS 方法，用于同时测定不同大鼠生物样品中的六种木脂素成分。口服 FZHY 剂量为 15g/kg 后，与正常大鼠相比，肝纤维化大鼠中五味子甲素（SIA）、五味子乙素（SIB）、五味子丙素（SIC）、五味子醇甲（SOA）、五味子醇乙（SOB）和五味子酯甲（STA）的药代动力学行为发生了显著变化，其 AUC（0-t）值分别增加了 235.09%、388.44%、223.30%、669.30%、295.08%和 267.63%（P<0.05）。组织分布结果表明，与正常大鼠相比，肝纤维化大鼠心、肺、脾、肾中 SIA、SIB、SOA 和 SOB 的含量在大多数时间点均显著增加（P<0.05）。同时，结果还表明，肝纤维化可延迟木脂素在肝脏中的达峰时间。
结论
研究结果证明，所建立的 UHPLC-MS/MS 方法可应用于正常和肝纤维化大鼠木脂素成分药代动力学和组织分布的比较研究。肝纤维化可改变 FZHY 给药后大鼠木脂素成分的药代动力学和组织分布特性。研究结果可能有助于指导该药的临床应用。
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