Moringa oleifera Leaf Extract Alleviates AFB1-Induced Hepatotoxicity and Oxidative Stress Through the PPARγ/Nrf2 Signaling Pathway

Aflatoxin B1 (AFB1), a potent carcinogen, is widely present in various crops, with limited prevention and treatment methods, continuously threatening food safety and public health. <i>Moringa oleifera</i> leaf extract (MOLE) is rich in bioactive compounds such as flavonoids, polysaccharides, triterpenes, and volatile oils, exhibiting antioxidant and anti-inflammatory potential. However, its specific effects and underlying mechanisms against AFB1-induced hepatotoxicity remain unclear. This study aimed to elucidate the alleviative effect of MOLE on AFB1 hepatotoxicity and its molecular mechanisms. In AFB1-induced mouse-liver tissue and hepatocyte models, MOLE significantly reduced the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Data indicated that MOLE treatment markedly suppressed AFB1-induced accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing antioxidant indicators such as total antioxidant capacity (T-AOC) and glutathione (GSH). Network pharmacology identified 50 bioactive components in MOLE and revealed 78 common targets with AFB1-induced hepatotoxicity. Protein-protein interaction analysis identified 10 core targets. Key active compounds included naringenin, quercetin, and luteolin. GO and KEGG enrichment results were closely associated with ROS-related pathways. Molecular docking demonstrated strong binding affinity between MOLE components and core targets, particularly with PPARG. Mechanistically, MOLE significantly increased PPARγ protein levels and upregulated Nrf2 protein expression. It also enhanced the mRNA expression of <i>HO-1</i>, <i>SOD</i>, <i>NQO1</i>, <i>CAT</i>, and <i>GPX1</i> and improved cellular total antioxidant capacity. Crucially, inhibiting PPARγ abolished the protective effects of MOLE and reversed its promotion of Nrf2. In conclusion, MOLE alleviates liver injury by binding to PPARγ to activate the Nrf2 pathway, thereby inhibiting AFB1-induced ROS accumulation.