Red yeast rice extract’s impact on liver health: a pharmacological and metabolomic exploration

作者：Mo Zhao, Yuwei Wang, Yingdong Lu, Zucheng Shang, Xin Zhao, Aimei Lu, S L Wang, Zhen Liu, Hongzheng Li · 发表于：Frontiers in Nutrition · 年份：2026 · DOI：10.3389/fnut.2026.1771594 · 研究领域：Microbial Metabolism and Applications、GABA and Rice Research、Protein Hydrolysis and Bioactive Peptides

Aims This study aimed to investigate the therapeutic mechanism of red yeast rice extract (RYRE) in high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) through untargeted metabolomics analysis and experimental validation. Methods An untargeted metabolomics analysis based on UHPLC-QTOF/MS was performed to identify differential metabolites in liver tissues. A NAFLD model was established in hamsters by HFD feeding. Forty hamsters were randomly allocated into four groups ( n = 10 per group): control (CON), model (MOD), red yeast rice extract (Xuezhikang, XZK), and simvastatin (SVT). Serum levels of lipids (TG, CHO, HDL-C, LDL-C), liver function parameters (ALT, AST, ALB, ALP, γ -GT, TBiL, DBiL, TBA), and inflammatory cytokines (TNF- α , IL-4, IL-1 β , TGF-β) were measured by biochemical assays and ELISA. Liver tissues were subjected to Oil Red O, hematoxylin–eosin (HE), and Masson staining for histopathological evaluation. Additionally, qPCR and immunohistochemistry were employed to investigate the underlying signaling pathways. Results XZK significantly reduced serum levels of DBiL, TBiL, TBA, CHO, TG, and LDL-C, while increasing HDL-C in HFD-fed hamsters. Both XZK and SVT markedly decreased pro-inflammatory cytokines. Untargeted metabolomics identified 135 differential metabolites between the MOD and XZK groups (83 down-regulated, 52 up-regulated), which were primarily involved in carbon metabolism, lipid metabolism, and hormone metabolism. Mechanistically, XZK...