1. Cordycepin ameliorates kidney injury by inhibiting gasdermin D-mediated pyroptosis of renal macrophages through nuclear factor kappa-B.
- Author
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Tang Z and Zhu Y
- Subjects
- Animals, Mice, Male, Kidney metabolism, Kidney drug effects, Kidney pathology, Mice, Inbred C57BL, Reperfusion Injury metabolism, Reperfusion Injury drug therapy, Reperfusion Injury pathology, Reperfusion Injury prevention & control, Gasdermins, Pyroptosis drug effects, Acute Kidney Injury metabolism, Acute Kidney Injury drug therapy, Acute Kidney Injury pathology, Acute Kidney Injury prevention & control, Macrophages metabolism, Macrophages drug effects, NF-kappa B metabolism, Deoxyadenosines pharmacology, Phosphate-Binding Proteins metabolism, Intracellular Signaling Peptides and Proteins metabolism
- Abstract
To explain the effect and mechanism of cordycepin (COR) in resisting acute kidney injury (AKI). Network pharmacology was employed to analyze the correlations between COR, AKI, and pyroptosis, as well as the action target of COR. A mouse model of AKI was established by ischemia reperfusion injury (IRI), and after treatment with COR, the renal function, tissue inflammatory cytokine levels, and pyroptosis-related signals were detected in mice. In in-vitro experiments, damage of renal macrophages was caused by the oxygen-glucose deprivation model, and pyroptosis indicators and inflammatory cytokine levels were assayed after COR treatment. Network pharmacological analysis revealed that nuclear factor kappa-B (NF-κB) was the primary action target of COR and that COR could inhibit kidney injury and tissue inflammation during IRI by inhibiting NF-κB-mediated gasdermin D cleavage. When NF-κB was inhibited, the effect of COR was weakened. COR in renal macrophages could inhibit pyroptosis and lower the levels of inflammatory cytokines, whose effect was associated with NF-κB. Our study finds that COR can play an anti-inflammatory role and inhibit the progression of AKI through the NF-κB-mediated pyroptosis, which represents its nephroprotective mechanism., (© 2024 Wiley Periodicals LLC.)
- Published
- 2024
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