Comparative Pharmacokinetic Study of Rhubarb Anthraquinones in Normal and Nonalcoholic Fatty Liver Disease Rats

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY European Journal of Drug Metabolism and Pharmacokinetics Pub Date : 2023-12-19 DOI:10.1007/s13318-023-00875-z

Fang Zhang, Rui Wu, Yanfang Liu, Shu Dai, Xinyan Xue, Xiaohong Gong, Yunxia Li

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Abstract

Background and Objectives

Rhubarb anthraquinones contain five main components, that is, rhein, emodin, aloe-emodin, chrysophanol, and physcion, which demonstrate good therapeutic effects on nonalcoholic fatty liver disease (NAFLD). However, research on its pharmacokinetics in NAFLD remains lacking. This study aimed to investigate the pharmacokinetic differences of rhubarb anthraquinones in normal and NAFLD rats.

Methods

This study developed an NAFLD rat model by high-fat diet feeding for 6 weeks. Normal and NAFLD groups were orally administered different rhubarb anthraquinones doses (37.5, 75, and 150 mg/kg). The concentration of the rhein, emodin, aloe-emodin, chrysophanol, and physcion in plasma was determined by high-performance liquid chromatography–ultraviolet.

Results

The results revealed significant differences in pharmacokinetic behavior between normal and NAFLD rats. Compared with normal rats, NAFLD rats demonstrated significantly increased maximum plasma concentration (C_max) and area under the plasma concentration–time curve (AUC_{0 → ∞}) of rhubarb anthraquinones (P < 0.05), as well as significantly prolonged time to reach maximum plasma concentration (T_max), terminal elimination half-life (t_1/2), and mean residence time (MRT) of rhubarb anthraquinones (P < 0.05).

Conclusions

This study indicates significant differences in the pharmacokinetics of rhubarb anthraquinones between the physiological and NAFLD states of rats. Rhubarb anthraquinone demonstrated a longer retention time and slower absorption rate in NAFLD rats and exhibited higher bioavailability and peak concentration. This finding provides important information for guiding the clinical use of rhubarb anthraquinones under pathological conditions.

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大黄蒽醌在正常大鼠和非酒精性脂肪肝大鼠中的药代动力学比较研究

背景和目的大黄蒽醌类化合物含有五种主要成分，即大黄酚、大黄素、芦荟大黄素、菊花酚和麝香草酚，对非酒精性脂肪肝（NAFLD）有良好的治疗效果。然而，关于其在非酒精性脂肪肝中的药代动力学研究仍然缺乏。本研究旨在探讨大黄蒽醌类药物在正常大鼠和非酒精性脂肪肝大鼠体内的药代动力学差异。正常组和非酒精性脂肪肝组分别口服不同剂量的大黄蒽醌（37.5、75 和 150 mg/kg）。结果显示，正常大鼠和非酒精性脂肪肝大鼠的药代动力学行为存在显著差异。与正常大鼠相比，非酒精性脂肪肝大鼠大黄蒽醌类药物的最大血浆浓度（Cmax）和血浆浓度-时间曲线下面积（AUC0 → ∞）均明显增加（P < 0.05），以及大黄蒽醌达到最大血浆浓度的时间（Tmax）、末端消除半衰期（t1/2）和平均停留时间（MRT）均明显延长（P < 0.05）。大黄蒽醌在非酒精性脂肪肝大鼠体内的滞留时间更长，吸收速度更慢，生物利用度和峰值浓度更高。这一发现为大黄蒽醌在病理状态下的临床应用提供了重要的指导信息。

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来源期刊

European Journal of Drug Metabolism and Pharmacokinetics 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.