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使用超高效液相色谱-串联质谱法研究提取物中三种生物活性二萜类化合物在正常和刀豆蛋白A诱导的肝损伤大鼠体内的比较药代动力学

Comparative Pharmacokinetics of Three Bioactive Diterpenoids of Extract in Normal and Con A-Induced Liver Injury Rats Using UPLC-MS/MS.

作者信息

Liu Fangle, Zeng Yun, Dai Pengyu, Huang Kaiwen, Zhang Kaihui, Tao Tao, Wang Meiqi, Zhu Chenchen, Lin Chaozhan

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Front Pharmacol. 2022 Jul 12;13:944949. doi: 10.3389/fphar.2022.944949. eCollection 2022.

Abstract

(Maxim.) Hara (), one of the source plants of "Xihuangcao", has been widely used as a Chinese folk herb with the concomitant function of both medicine and foodstuff for the prevention and treatment of liver disease. Diterpenoids were considered as the major bioactive components in , responsible for their effect on hepatoprotection in previous phytochemical and pharmacological studies, while few comparative pharmacokinetic studies have been conducted under the physiological and pathological conditions. To reveal the difference in the pharmacokinetics process of extract (RSE) in normal and Con A-induced liver injury rats, a rapid ultra-high-pressure liquid chromatography-tandem mass spectrometry method (total running time: 5 min) was established to simultaneously determine three bioactive diterpenoids (enmein, epinodosin, and isodocarpin) in rat plasma. The results showed significant differences in the pharmacokinetic properties of three analytes between the physiological and pathological states. Compared with normal rats, the AUC of the three analytes was remarkably higher in liver injury rats, while the T, T, and MRT were shortened. It indicated that RSE has higher exposure and quicker elimination in liver injury rats than that in normal rats. Our results suggested that the pharmacokinetics of hepatoprotective medications was affected by liver injury, which prospected to provide essential information for guiding the healthcare and clinical application of in pathological states.

摘要

(马克西姆。)原儿茶酸()是“溪黄草”的源植物之一,作为一种具有药食两用功能的中国民间草药,已被广泛用于预防和治疗肝脏疾病。在先前的植物化学和药理学研究中,二萜类化合物被认为是原儿茶酸中的主要生物活性成分,负责其对肝脏的保护作用,而在生理和病理条件下进行的比较药代动力学研究较少。为了揭示原儿茶酸提取物(RSE)在正常大鼠和刀豆蛋白A诱导的肝损伤大鼠中药代动力学过程的差异,建立了一种快速超高效液相色谱 - 串联质谱法(总运行时间:5分钟),用于同时测定大鼠血浆中的三种生物活性二萜类化合物(延命草素、表诺多辛和异柯卡品)。结果表明,三种分析物在生理和病理状态下的药代动力学性质存在显著差异。与正常大鼠相比,肝损伤大鼠中三种分析物的AUC显著更高,而T、T和MRT缩短。这表明RSE在肝损伤大鼠中的暴露量更高,消除速度比正常大鼠更快。我们的结果表明,肝损伤会影响保肝药物的药代动力学,这有望为指导原儿茶酸在病理状态下的医疗保健和临床应用提供重要信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b4/9323086/644d17467998/fphar-13-944949-g001.jpg

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