α-Lipoic acid alleviates dextran sulfate sodium salt-induced ulcerative colitis via modulating the Keap1-Nrf2 signaling pathway and inhibiting ferroptosis

α-硫辛酸通过调节Keap1-Nrf2信号通路抑制铁死亡减轻葡聚糖硫酸钠诱发的溃疡性结肠炎

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作者:Peng Jiang #, Zongzhen Zhai #, Linxian Zhao, Kai Zhang, Liwei Duan

Background

Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disease with severe diarrhea, fatigue and weight loss. α-Lipoic acid (LA), a well-known antioxidant, is able to scavenge reactive oxygen species (ROS) and maintain a healthy cellular redox state. However, the role of LA in protecting IBD is still unclear. Hence the

Conclusion

Taken together, this study's findings suggest that LA could be considered as a therapeutic agent protecting against IBD. © 2023 Society of Chemical Industry.

Results

Here, our findings showed that LA significantly alleviated UC symptoms and the overproduction of pro-inflammatory cytokines in UC mice. In addition, LA treatment inhibited intestinal cell apoptosis by regulating the expression levels of p53/caspase-3 pathway-related protein in UC mice. Meanwhile, the inhibitory effects of LA on colonic oxidative stress and ferroptosis were revealed. Our study further demonstrated that LA treatment could regulate the Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Interestingly, we confirmed that LA inhibited ferroptosis by attenuating endoplasmic reticulum stress and suppressing apoptosis in erastin-induced ferroptosis model in vitro.

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