Fang Zhang, Rui Wu, Yanfang Liu, Shu Dai, Xinyan Xue, Xiaohong Gong, Yunxia Li
{"title":"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","authors":"Fang Zhang, Rui Wu, Yanfang Liu, Shu Dai, Xinyan Xue, Xiaohong Gong, Yunxia Li","doi":"10.1007/s13318-023-00875-z","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and Objectives</h3><p>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.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>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.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>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 (<i>C</i><sub>max</sub>) and area under the plasma concentration–time curve (AUC<sub>0 → ∞</sub>) of rhubarb anthraquinones (<i>P</i> < 0.05), as well as significantly prolonged time to reach maximum plasma concentration (<i>T</i><sub>max</sub>), terminal elimination half-life (<i>t</i><sub>1/2</sub>), and mean residence time (MRT) of rhubarb anthraquinones (<i>P</i> < 0.05).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>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.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":"81 1","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparative Pharmacokinetic Study of Rhubarb Anthraquinones in Normal and Nonalcoholic Fatty Liver Disease Rats\",\"authors\":\"Fang Zhang, Rui Wu, Yanfang Liu, Shu Dai, Xinyan Xue, Xiaohong Gong, Yunxia Li\",\"doi\":\"10.1007/s13318-023-00875-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background and Objectives</h3><p>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>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 (<i>C</i><sub>max</sub>) and area under the plasma concentration–time curve (AUC<sub>0 → ∞</sub>) of rhubarb anthraquinones (<i>P</i> < 0.05), as well as significantly prolonged time to reach maximum plasma concentration (<i>T</i><sub>max</sub>), terminal elimination half-life (<i>t</i><sub>1/2</sub>), and mean residence time (MRT) of rhubarb anthraquinones (<i>P</i> < 0.05).</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusions</h3><p>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. 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Comparative Pharmacokinetic Study of Rhubarb Anthraquinones in Normal and Nonalcoholic Fatty Liver Disease Rats
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 (Cmax) and area under the plasma concentration–time curve (AUC0 → ∞) of rhubarb anthraquinones (P < 0.05), as well as significantly prolonged time to reach maximum plasma concentration (Tmax), terminal elimination half-life (t1/2), 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.
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.