Role of ginsenoside Rg1 as a PPAR-γ activator in protecting against manganese-induced hepatotoxicity: Insights into the TLR4/MyD88/MAPK signaling pathway

This study investigates the protective effect of ginsenoside Rg1 against manganese (Mn)-induced hepatotoxicity, highlighting its role as a PPAR-gamma activator and its impact on TLR4/MyD88/MAPK pathway. Manganese induces liver damage through mechanisms involving oxidative stress and inflammation. Rg1, a principal bioactive compound of ginseng, significantly alleviates Mn-induced liver injury. Rg1 markedly enhances the activities of SOD, GSH, and CAT, while reducing levels of MDA and ROS, indicating an improvement in antioxidant defense capacity. Furthermore, Rg1 decreases inflammatory markers iNOS, TNF-alpha, IL-6, IL-12 and NO levels, underscoring its strong anti-inflammatory effects. Importantly, as a PPAR-gamma activator, Rg1 upregulates PPAR-gamma expression, subsequently inhibiting TLR4/MyD88/MAPK pathway. Additionally, silencing of PPAR-gamma diminishes the protective effects of Rg1, while overexpression of PPAR-gamma enhances them. The findings conclude that Rg1 exerts significant hepatoprotective effects against manganese-induced damage by activating PPAR-gamma and modulating TLR4/MyD88/MAPK pathway, positioning it as a promising candidate for the treatment of Mninduced hepatotoxicity.