Study on the mechanism of cordycepin inhibiting ferroptosis via the Nrf2/HO-1 pathway to delay the transformation from AKI to CKD

BAI Mengqi; LI Junhu; ZHAO Zhibo; ZHOU Xiaoshuang

doi:10.6039/j.issn.1001-0408.2026.11.08

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Study on the mechanism of cordycepin inhibiting ferroptosis via the Nrf2/HO-1 pathway to delay the transformation from AKI to CKD

更新时间：2026-06-10

- Study on the mechanism of cordycepin inhibiting ferroptosis via the Nrf2/HO-1 pathway to delay the transformation from AKI to CKD
- ZHONGGUO YAOFANG Vol. 37, Issue 11, Pages: 1428-1433(2026)
- 作者机构：
  
  1.山西中医药大学第三临床学院，山西晋中　030619
  2.山西省人民医院肾内科，太原　030012
  3.山西医科大学第五临床医学院肾内科，太原　030012
  4.山西省人民医院肾脏病大数据中心，太原　030012
  5.肾脏病山西省重点实验室，太原　030012
  6.山西医科大学教育部慢性肾脏病医药基础研究创新中心，太原　030001
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.11.08
  CLC： R965;R285
- Received：24 December 2025，
  
  Revised：2026-05-15，
  
  Accepted：18 May 2026，
  
  Published：15 June 2026
- 稿件说明：
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白梦琦,李俊虎,赵志波,等.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 [J].中国药房,2026,37(11):1428-1433.

BAI Mengqi,LI Junhu,ZHAO Zhibo,et al.Study on the mechanism of cordycepin inhibiting ferroptosis via the Nrf2/HO-1 pathway to delay the transformation from AKI to CKD[J].ZHONGGUO YAOFANG,2026,37(11):1428-1433.
白梦琦,李俊虎,赵志波,等.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 [J].中国药房,2026,37(11):1428-1433. DOI： 10.6039/j.issn.1001-0408.2026.11.08.

BAI Mengqi,LI Junhu,ZHAO Zhibo,et al.Study on the mechanism of cordycepin inhibiting ferroptosis via the Nrf2/HO-1 pathway to delay the transformation from AKI to CKD[J].ZHONGGUO YAOFANG,2026,37(11):1428-1433. DOI： 10.6039/j.issn.1001-0408.2026.11.08.

摘要

目的

研究虫草素延缓急性肾损伤（AKI）向慢性肾脏病（CKD）（以下简称“AKI-CKD”）转化的作用机制。

方法

采用网络药理学和生物信息学分析并预测虫草素延缓AKI-CKD的信号通路及其与铁死亡途径的关系。采用细胞实验对预测结果进行验证：将人肾小管上皮细胞HK-2分为空白组、虫草素组、模型组、H

+虫草素组，除空白组和虫草素组外，其余各组加入150 μmol/L H

处理72 h以诱导细胞持续性氧化应激损伤；虫草素（40 μmol/L）干预72 h后，检测细胞中谷胱甘肽过氧化物酶4（GPX4）、长链脂酰辅酶A合成酶4（ACSL4）、核转录因子红系2相关因子2（Nrf2）、血红素加氧酶1（HO-1）蛋白和mRNA表达水平。另在H

+虫草素的基础上引入Nrf2抑制剂ML385以验证Nrf2/HO-1通路的作用。

结果

网络药理学及生物信息学分析结果显示，虫草素与AKI-CKD及铁死亡相关的交集基因有42个，其中38个被注释为铁死亡相关基因；HO-1与Nrf2可能是虫草素抑制铁死亡的重要靶点，虫草素与Nrf2、HO-1蛋白的结合能分别为－8.5、－6.7 kcal/mol。细胞实验结果显示，与模型组比较，H

+虫草素组细胞中GPX4、Nrf2、HO-1蛋白和mRNA表达水平均显著升高（

＜0.05），ACSL4蛋白和mRNA表达水平均显著降低（

＜0.05）；加入Nrf2抑制剂ML385后，虫草素对上述蛋白和mRNA的作用被显著逆转（

＜0.05）。

结论

虫草素可通过激活Nrf2/HO-1通路抑制铁死亡，减轻肾小管上皮细胞持续性氧化应激损伤，延缓AKI-CKD进展。

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

+cordycepin group. Except for the blank group and cordycepin group， all other groups were treated with 150 μmol/L H

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

+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 （

＜0.05），while the protein and mRNA expression levels of ACSL4 were significantly decrease

d （

＜0.05） in the H

+cordycepin group. After the addition of the Nrf2 inhibitor ML385， the effects of cordycepin on the above proteins and mRNA were significantly reversed （

＜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.

关键词

Keywords

references

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