Study on the mechanism of cordycepin inhibiting ferroptosis via the Nrf2/HO-1 pathway to delay the transformation from AKI to CKD
- VernacularTitle:虫草素通过Nrf2/HO-1通路抑制铁死亡延缓AKI向CKD转化的作用机制研究
- Author:
Mengqi BAI
1
;
Junhu LI
2
;
Zhibo ZHAO
2
;
Xiaoshuang ZHOU
2
Author Information
1. The Third Clinical College，Shanxi University of Chinese Medicine，Shanxi Jinzhong 030619，China
2. Dept. of Nephrology，Shanxi Provincial People’s Hospital，Taiyuan 030012，China;Dept. of Nephrology，the Fifth Clinical Medical College，Shanxi Medical University，Taiyuan 030012，China;Big Data Center for Kidney Diseases，Shanxi Provincial People’s Hospital，Taiyuan 030012，China;Shanxi Province Key Laboratory of Kidney Diseases，Taiyuan 030012，China
- Publication Type:Journal Article
- Keywords:
cordycepin;
acute kidney injury;
chronic kidney disease;
Nrf2/HO-1 pathway;
ferroptosis;
network pharmacology;
bioinformatics
- From:
China Pharmacy
2026;37(11):1428-1433
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the mechanism of cordycepin in delaying the transformation from acute kidney injury （AKI） to chronic kidney disease （CKD） （short for “AKI-CKD”）. METHODS Network pharmacology and bioinformatics were used to analyze and predict the signaling pathways of cordycepin in delaying AKI-CKD progression and its relationship with the ferroptosis pathway. Cell experiments were performed to verify the predicted results. Human renal tubular epithelial HK-2 cells were divided into blank group， cordycepin group， model group， and H 2 O 2 +cordycepin group. Except for the blank group and cordycepin group， all other groups were treated with 150 μmol/L H 2 O 2 for 72 h to induce persistent oxidative stress injury in cells. After 72 h of cordycepin （40 μmol/L） intervention， the protein and mRNA expression levels of glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4），nuclear factor-erythroid 2-related factor 2（Nrf2）， and heme oxygenase-1 （HO-1） in cells were detected. Furthermore， the Nrf2 inhibitor ML385 was added on the basis of H 2 O 2 +cordycepin to verify the role of the Nrf2/HO-1 pathway. RESULTS Network pharmacology and bioinformatics analysis showed that there were 42 overlapping genes related to AKI-CKD and ferroptosis that interact with cordycepin ferroptosis， among which 38 were annotated as ferroptosis-related genes. HO-1 and Nrf2 might be important targets for cordycepin to inhibit ferroptosis. The binding energies of cordycepin with Nrf2 and HO-1 proteins were －8.5 and －6.7 kcal/mol， respectively. Cell experiments showed that compared with the model group， the protein and mRNA expression levels of GPX4， Nrf2 and HO-1 were significantly increased （ P ＜0.05），while the protein and mRNA expression levels of ACSL4 were significantly decrease d （ P ＜0.05） in the H 2 O 2 +cordycepin group. After the addition of the Nrf2 inhibitor ML385， the effects of cordycepin on the above proteins and mRNA were significantly reversed （ P ＜0.05）. CONCLUSIONS Cordycepin can inhibit ferroptosis by activating the Nrf2/HO-1 pathway， reduce persistent oxidative stress injury of renal tubular epithelial cells， and delay the progression of AKI-CKD.
