Comprehensive metabolic profiling and enzyme kinetics of cis-2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside in normal and hyperlipidemic rats

作者：J U N T A O Qiu, Bin Yao, Qing Yu, Jiajie Wang, Lingling Huang, Jiale Chen, Yufeng Lu, Chunying Wang · 发表于：Figshare · 年份：2026 · DOI：10.6084/m9.figshare.33075790.v1 · 研究领域：Phytochemistry and biological activity of medicinal plants、Mangiferin and Mango Extracts、Biological and pharmacological studies of plants

Cis- 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside ( cis -THSG), a photoisomer of the major bioactive component in Polygoni Multiflori Radix Praeparata (He-Shou-Wu), has enhanced hypolipidemic activity but is associated with idiosyncratic hepatotoxicity. Its metabolic fate under pathological conditions and key clearance enzymes remain unclear.This study aimed to compare metabolite profiles of cis -THSG in normal and hyperlipidemic rats in vivo and in vitro , identify metabolites, and characterise enzyme kinetics in rat liver microsomes (RLMs) and major CYP450 isoforms. Metabolites in plasma, urine, faeces, bile, and intestinal bacteria incubation fluids were analysed by UHPLC-Q-TOF-MS/MS. Enzymatic kinetics and CYP450 isoforms were investigated via chemical inhibition assays.A total of 27 metabolites were characterised; cis -THSG underwent rapid glucoside hydrolysis, and its aglycone underwent phase I and II reactions. Hyperlipidaemia reduced metabolites to 20 and markedly increased plasma cis -THSG and aglycone abundance. Kinetic parameters were K m 32.86 μmol/L, V max 0.7285 μmol/(min·mg protein), CL int 0.02217 L/(min·mg protein). Rat liver microsomal CYP isoforms analogous to human CYP3A4 and CYP2C9 mediated cis -THSG oxidative metabolism.This study provides the first comprehensive metabolite map of cis-THSG, identifies its aglycone as a potential bioactive form, and reveals a disease-related metabolic shift. CYP phenotyping offers a mechanistic basi...