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

Abstract

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