{"title":"虫草素通过核因子卡巴-B抑制气敏素 D 介导的肾巨噬细胞热凋亡,从而改善肾损伤","authors":"Zhiling Tang, Yu Zhu","doi":"10.1002/jbt.23824","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 9","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cordycepin ameliorates kidney injury by inhibiting gasdermin D-mediated pyroptosis of renal macrophages through nuclear factor kappa-B\",\"authors\":\"Zhiling Tang, Yu Zhu\",\"doi\":\"10.1002/jbt.23824\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"38 9\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.23824\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.23824","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Cordycepin ameliorates kidney injury by inhibiting gasdermin D-mediated pyroptosis of renal macrophages through nuclear factor kappa-B
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.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.