Dihydromyricetin reduces hepatic lipids and improves metabolic markers in murine MASLD models

Dihydromyricetin (DHM) is a food-derived flavonoid widely investigated as a nutraceutical candidate for metabolic dysfunction–associated steatotic liver disease (MASLD) in preclinical models; however, its overall efficacy in diet-induced MASLD/NAFLD models has not been systematically quantified. This PRISMA 2020 systematic review and meta-analysis was registered in PROSPERO (CRD420251119087). PubMed, Embase, Web of Science Core Collection, the Cochrane Library, and four major Chinese databases were searched from inception to December 15, 2025. Controlled murine studies comparing DHM monotherapy with high-fat diet controls were included. Random-effects meta-analyses pooled standardized mean differences (SMDs) with 95% confidence intervals; risk of bias was assessed using SYRCLE’s tool. Fourteen controlled studies were included. Compared with controls, DHM reduced hepatic triglycerides and total cholesterol, improved liver enzymes (ALT, AST, ALP), and decreased body weight and liver index. DHM improved serum lipid profiles (lower total cholesterol and LDL; higher HDL) and glucose homeostasis (lower fasting glucose and insulin). Antioxidant defenses increased (SOD, CAT, GSH, GSH-Px) with reduced malondialdehyde, while inflammatory markers (TNF-α and IL-6) decreased. At the signaling level, DHM increased the pAMPK/AMPK ratio. Heterogeneity was moderate to high for several outcomes, partly explained by dose and treatment duration. In murine diet-induced MASLD/NAFLD models, DHM shows promising multidomain benefits across various physiological outcomes, though some variability remains due to differences in study design. More standardized preclinical designs and well-controlled nutraceutical/clinical studies are needed to define clinically relevant, bioavailable dosing and efficacy. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251119087, PROSPERO, Identifier CRD420251119087.