Department of Urology Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
Department of Intensive Care Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
J Biochem Mol Toxicol. 2024 Sep;38(9):e23824. doi: 10.1002/jbt.23824.
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.
为了阐明蛹虫草素（COR）在抵抗急性肾损伤（AKI）中的作用和机制。采用网络药理学分析 COR、AKI 和细胞焦亡之间的相关性以及 COR 的作用靶点。通过缺血再灌注损伤（IRI）建立 AKI 小鼠模型，并用 COR 处理后，检测小鼠的肾功能、组织炎症细胞因子水平和细胞焦亡相关信号。在体外实验中，用氧葡萄糖剥夺模型造成肾巨噬细胞损伤，并用 COR 处理后测定细胞焦亡指标和炎症细胞因子水平。网络药理学分析表明，核因子 kappa-B（NF-κB）是 COR 的主要作用靶点，COR 可通过抑制 NF-κB 介导的 gasdermin D 裂解来抑制 IRI 期间的肾损伤和组织炎症。当抑制 NF-κB 时，COR 的作用减弱。COR 在肾巨噬细胞中可以抑制细胞焦亡并降低炎症细胞因子的水平，其作用与 NF-κB 有关。本研究发现，COR 通过 NF-κB 介导的细胞焦亡发挥抗炎作用并抑制 AKI 的进展，这代表了其肾脏保护机制。
