Cordycepin ameliorates ischemia/reperfusion-induced acute kidney injury via inhibiting apoptosis and necroptosis

Articles in Press

Document Type : Original Article

Authors

1 Department of Nephrology, Fifth Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030012, China

2 Department of Nephrology, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, 030012, China

3 Big Data Center of Kidney Disease, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, 030012, China

4 Department of Traditional Chinese Medicine, Yan’an Baota District People’s Hospital, Yan’an, Shaanxi, 716000, China

5 Shanxi Provincial Key Laboratory of Kidney Disease, Taiyuan, Shanxi, 030012, China

6 Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030012, China

10.22038/ijbms.2026.92098.19878

Abstract

Objective(s): Cordycepin (COR) is a natural bioactive compound derived from Cordyceps militaris. Relevant studies have shown that COR can alleviate kidney damage, but the underlying mechanism of its action in the treatment of acute kidney injury (AKI) remains to be further clarified.
Materials and Methods: The GSE148420 dataset and GeneCards were used to identify AKI-related targets. GeneCards was used to obtain ischemia/reperfusion (I/R)-related targets. BATMAN 1.0 and GeneCards were used to identify potential drug targets of COR. Renal function, tissue damage, and molecular markers were assessed to explore the effects of COR on apoptosis and necroptosis in the treatment of AKI.
Results: Network pharmacological analysis showed that AKI and COR shared 28 drug targets. Enrichment analysis showed that the targets were involved in signaling pathways, including apoptosis and necroptosis. In vitro experiments revealed that COR alleviated hypoxia/re-oxygenation(H/R)-induced HK-2 cells injury by reducing the expression of Bax and cleaved-Caspase3 while increasing the expression of Bcl-2. Necroptosis was lessened under COR treatment in vitro and in H/R-induced HK-2 cells by reducing the expression of RIPK1, RIPK3, MLKL, and p-MLKL. COR and Nec-1 (a RIPK1 inhibitor) had the same inhibitory effect, confirming the role of COR in alleviating AKI by inhibiting RIPK1-driven necroptosis. COR alleviated AKI by ameliorating renal morphology injury and pathological injury in vivo, manifested as a decrease in Scr and BUN levels, a significant reduction in the mRNA expression levels of KIM-1 and NGAL, and a decrease in p-MLKL at the immunohistochemical level.
Conclusion: COR may ameliorate I/R-induced AKI by inhibiting apoptosis and RIPK1/RIPK3/p-MLKL-mediated necroptosis.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

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Available Online from 17 June 2026

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