Ginsenoside Rb1 targets the NRF2-PPARγ-ACSL4 axis to inhibit PTECs ferroptosis

The experimental results demonstrated that Rb1 administration significantly ameliorated renal dysfunction, attenuated tubular necrosis and inflammatory responses, while markedly suppressing ferroptosis-related indicators. Strikingly, Rb1 exhibited superior efficacy to Fer-1 in preventing ferroptosis in proximal tubular epithelial cells (PTECs) in vitro. Nuclear factor erythroid 2-related factor 2 (NRF2) was verified as a direct target for Rb1's ferroptosis-inhibitory effect. Mechanistic studies revealed that Rb1 selectively inhibits lipid peroxidation-the biochemical hallmark of ferroptosis-by activating the NRF2-PPARγ-ACSL4 axis.  CONCLUSION: Given its established safety profile in human use, Rb1 represents a potential therapeutic agent for preventing and treating AKI, providing scientific evidence for its application in anti-ferroptosis therapy..