Paeoniflorin and NAFLD: A Systematic Review and Meta-Analysis of Animal Studies With Mechanistic Insights

Nonalcoholic fatty liver disease (NAFLD) is a major metabolic liver disorder with limited pharmacological options. Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora, has shown hepatometabolic effects in experimental studies, but its overall efficacy in NAFLD models remains unclear. We searched PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, VIP, and CBM from inception to January 2026 for controlled animal studies evaluating PF in diet-induced NAFLD models. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using SYRCLE's tool. Weighted mean differences or standardized mean differences with 95% confidence intervals were pooled using random-effects models. Ten studies were included, all using diet-induced models. PF treatment was associated with improvements in lipid metabolism, liver injury, glucose homeostasis, inflammation, and oxidative stress, including reductions in total cholesterol, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, body weight, fasting blood glucose, insulin resistance indices, tumor necrosis factor-α, and malondialdehyde, together with increased superoxide dismutase activity. High-density lipoprotein cholesterol showed no consistent improvement. Mechanistic findings suggested that PF may activate AMP-activated protein kinase, inhibit sterol regulatory element-binding protein-1c/fatty acid synthase-mediated lipogenesis, and modulate inflammatory and oxidative-stress pathways. However, substantial heterogeneity and incomplete reporting of randomization, allocation concealment, and blinding limited confidence in the evidence. PF showed promising preclinical effects in NAFLD, but further well-designed animal studies and clinical investigations are needed to clarify dose-response relationships, safety, and translational relevance.