Pharmacological effects of dihydromyricetin in preclinical models of NAFLD: a systematic review and meta-analysis stratified by dose and duration.

BACKGROUND: Dihydromyricetin (DHM), a naturally occurring flavonoid, has shown beneficial effects in preclinical models of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the extent to which dose and treatment duration influence its pharmacological effects remains to be systematically evaluated. OBJECTIVE: This study aimed to evaluate the pharmacological effects of DHM in preclinical models of NAFLD and to further explore the potential influence of treatment dose and duration on these effects using subgroup analyses. METHODS: Studies were identified through systematic searches of six electronic databases. Eligible animal studies were included according to predefined criteria. Risk of bias (RoB) was assessed using the SYRCLE tool. Quantitative synthesis was performed using RevMan (version 5.4). To further explore the potential influence of treatment dose and duration, three-dimensional (3D) visualization plots and radar charts were generated using OriginPro 2024. RESULTS: A total of 13 studies encompassing 14 independent experiments with 316 animals were included. DHM was associated with improvements in hepatic and serum lipid profiles, liver enzyme levels, and glucose homeostasis. Heterogeneity remained high across strata despite subgroup analyses by dose and duration. Integrated 3D plots and radar charts visually illustrated these findings. CONCLUSION: DHM exhibited favorable pharmacological effects in preclinical models of NAFLD, with lipid-related outcomes appearing more sensitive to dose and liver enzyme outcomes showing greater responsiveness to treatment duration. Persistent heterogeneity highlights the need for standardized experimental protocols in future preclinical research. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251124831, identifier CRD420251124831.