1. Academic Validation
  2. Bergenin inhibits ferritinophagy and ferroptosis in cisplatin-induced acute kidney injury by activating the p-GSK3β/Nrf2/PPARγ pathway

Bergenin inhibits ferritinophagy and ferroptosis in cisplatin-induced acute kidney injury by activating the p-GSK3β/Nrf2/PPARγ pathway

  • Int Immunopharmacol. 2025 Feb 6:147:114004. doi: 10.1016/j.intimp.2024.114004.
Jianqiang Hu 1 Yan Zhang 1 Yanmin Zhang 1 Ningmohan Shi 1 Yufan Miu 1 Jing Huang 1 Mochi Miao 1 Xinxin Ci 2
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130001, China.
  • 2 Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130001, China. Electronic address: cixinxin@jlu.edu.cn.
Abstract

Ferroptosis plays a key role in cisplatin-induced acute kidney injury (AKI). Bergenin, which is extracted from Ardisiae Japonicae Herba and has long been used in folk tea and herbal tea drinks, is known to activate Nrf2 and has anti-inflammatory and antioxidant properties, however, its protective influence on CI-AKI has not been elucidated. We used models of cisplatin-induced nephrotoxicity in vitro and CI-AKI models in vivo. In vitro, we found that Ferroptosis and ferritinophagy biomarkers were strongly regulated by bergenin treatment. Mechanistic experiments demonstrated that bergenin bound to and phosphorylated GSK3β, which inhibited its activity, to promote the nuclear translocation of Nrf2 and its subsequent binding to the PPARγ promoter sequence to activate PPARγ. However, the protective effects of bergenin on Ferroptosis and ferritinophagy in cisplatin-exposed HK-2 cells were diminished when Nrf2 or PPARγ was inhibited. In vivo, bergenin effectively inhibited renal damage induced by cisplatin. Furthermore, bergenin attenuated ferritinophagy-mediated Ferroptosis caused by cisplatin; these effects were abolished in Nrf2 knockout mice. Our findings revealed that bergenin effectively protected against ferritinophagy and Ferroptosis in CI-AKI, which was largely dependent on the activation of the p-GSK3β/Nrf2/PPARγ pathway.

Keywords

Bergenin; CI-AKI; Ferritinophagy; Ferroptosis; Nrf2; PPARγ.

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