Effects of Gamisoyo-San, a Traditional Herbal Medicine, on Antioxidant Phase II Enzymes via Akt-Erk-Nrf2 Pathway

Abstract Background Oxidative stress plays a pivotal role in liver damage, leading to various pathologies, such as hepatic fibrosis and hepatocellular injury. While natural products have garnered attention for their hepatoprotective effects, the potential of Gamisoyo-San (GSS) in mitigating oxidative stress-induced liver injury remains insufficiently studied. Methods This study evaluated the protective effects of GSS against arachidonic acid (AA) and iron-induced cytotoxicity in HepG2 cells. Hepatoprotective effects were assessed through cell viability assays, ROS measurement, mitochondrial membrane potential analysis, and immunoblotting to investigate the involvement of antioxidant signaling pathways, including Erk, Akt, and Nrf2/HO-1. Results GSS treatment significantly improved cell viability, reduced ROS generation, and ameliorated mitochondrial dysfunction induced by AA + iron-mediated oxidative stress. GSS also activated Erk and Akt pathways, which enhanced the nuclear translocation of Nrf2 and upregulated HO-1 expression. Inhibition of the Erk or Akt pathways impaired the hepatoprotective effects of GSS, demonstrating their essential role in mediating these protective actions. Conclusion Our findings suggest that GSS protects hepatocytes against oxidative stress-induced damage by modulating the Erk, Akt, and Nrf2/HO-1 pathways. These results highlight GSS as a promising herbal medicine for the pharmaco-acupuncture with therapeutic potential for oxidative stress-related liver diseases.