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

Area of Science:

• Nephrology
• Pharmacology
• Cell Biology

Background:

• Ferroptosis, a cell death pathway linked to lipid peroxidation, is a key factor in acute kidney injury (AKI).
• Current ferroptosis inhibitors like Ferrostatin-1 (Fer-1) have limitations.
• Ginsenoside Rb1 (Rb1), from Panax ginseng, shows potential for inhibiting ferroptosis.

Purpose of the Study:

• To investigate the therapeutic effects and mechanisms of Rb1 in treating AKI.
• To compare Rb1's efficacy against Fer-1 in preventing ferroptosis in kidney cells.

Main Methods:

• Evaluated renal function, tissue damage, and ferroptosis markers in mice and HK-2 cells.
• Utilized network pharmacology and molecular docking to identify Rb1 targets.
• Employed transcriptome sequencing and in vivo/in vitro validation to elucidate mechanisms.

Main Results:

• Rb1 significantly improved renal function and reduced kidney damage and inflammation in AKI models.
• Rb1 demonstrated superior ferroptosis inhibition compared to Fer-1 in proximal tubular epithelial cells.
• Identified Nuclear factor erythroid 2-related factor 2 (NRF2) as a direct target, with Rb1 activating the NRF2-PPARγ-ACSL4 axis to inhibit lipid peroxidation.

Conclusions:

• Rb1 effectively mitigates AKI by inhibiting ferroptosis through the NRF2-PPARγ-ACSL4 pathway.
• Rb1's established safety profile and superior efficacy suggest it as a potential therapeutic agent for AKI.
• Provides scientific evidence for Rb1's role in anti-ferroptosis therapy for kidney diseases.