Preclinical evaluation of puerarin for the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis

Background: Kudzu root is commonly prescribed in traditional Chinese medicine for non-alcoholic fatty liver disease (NAFLD). Its key active ingredient, puerarin, has shown promising protective effects in experimental NAFLD models. Yet the overall efficacy and the main biological mechanisms have not been systematically assessed. Objective: This meta-analysis will synthesize evidence from animal studies to determine how puerarin influences liver-related outcomes in NAFLD. It will also summarize the mechanistic pathways that may account for these effects. Method: Literature retrieval was performed up to September 2025, encompassing eight databases. The risk of bias in the included studies was evaluated using the SYRCLE assessment tool. Data analyses were then performed in Stata 15. The primary outcome included triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Secondary outcome comprised interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px). Subgroup analyses, publication bias assessments, and sensitivity analyses were performed to ensure the robustness. Results: 20 studies were included, involving 331 animals. Puerarin treatment significantly reduced levels of TG, TC, and LDL-C, while improving HDL-C in animal models of NAFLD. Additionally, puerarin significantly upregulated antioxidant indicators SOD and GSH-Px and lowered MDA levels. Furthermore, it inhibited the expression of inflammatory factors IL-6, IL-1β, and TNF-α. Conclusion: This meta-analysis concludes that puerarin demonstrates substantial liver-protective effects in NAFLD models by regulating lipid metabolism, anti-inflammatory, and antioxidant. Collectively, these finding lays a solid evidence-based foundation for the subsequent advancement of clinical translation research and the in-depth exploration of its underlying mechanisms. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, Identifier CRD420251170089.