Ginsenoside Rg1 Attenuates Renal Ischemia-Reperfusion Injury and Fibrosis by Suppressing Pro-Inflammatory Macrophage Activation

Objective: This study aimed to investigate the protective effects and underlying mechanisms of ginsenoside Rg1 in renal ischemia-reperfusion injury, with a focus on oxidative stress, macrophage polarization, and prevention of early profibrotic responses. Methods: An in vivo mouse renal IRI model and an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model using RAW264.7 macrophages were employed to evaluate renal function, oxidative stress, macrophage polarization, pro-inflammatory cytokine expression, and activation of the STING-NF-κB signaling pathway. Results: Rg1 alleviated renal tubular injury, preserved renal function, and reduced oxidative stress and tubular apoptosis in IRI mice. It also inhibited systemic leukocyte activation and local inflammatory cell infiltration. In vitro, Rg1 suppressed OGD/R-induced M1 polarization, pro-inflammatory cytokine expression, and ROS accumulation, and inhibited activation of the STING-NF-κB signaling pathway. Additionally, Rg1 attenuated early renal fibrosis post-IRI. Conclusion: Rg1 exerts dual protective effects against renal IRI by reducing oxidative stress and restraining macrophage-mediated inflammation. These findings highlight Rg1 as a promising therapeutic candidate for ischemic kidney injury. Keywords: Ginsenoside Rg1, renal ischemia-reperfusion injury, acute kidney injury, macrophage polarization, STING-NF-κB pathway, renal fibrosis