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Background <p>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. </p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月11日

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  • Su-Jin Bae,
  • Hyo-Gi Park,
  • Sun-Dong Park,
  • Young Woo Kim

摘要

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.