{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16"],"submitter":["Liu Z"],"pubmed_abstract":["Pyroptosis, a form of programmed cell death driven by the NLRP3 inflammasome, is a key contributor to inflammation in various diseases. This study aimed to investigate the anti-inflammatory mechanisms of cordycepin, focusing on its role in macrophage pyroptosis. Molecular docking analysis was performed to evaluate the binding affinity of cordycepin to key pyroptosis-related proteins, including NLRP3, Caspase-1, and GSDMD. RAW264.7 cells were pre-treated with cordycepin to assess its effects on pyroptosis. Key measurements included reactive oxygen species (ROS) levels, xanthine oxidase (XO) activity, and the expression of NLRP3, Caspase-1, and GSDMD. Additionally, lactate dehydrogenase (LDH) release, interleukin (IL)-1β and IL-18 levels in the culture supernatant, and macrophage cell death rates were evaluated using Hoechst 33342/PI dual staining. The results demonstrated that cordycepin exhibits strong binding affinity for NLRP3, Caspase-1, and GSDMD. Cordycepin pre-treatment significantly reduced ROS levels and XO activity, inhibited the expression of NLRP3, cleaved-Caspase-1, and cleaved-GSDMD, and decreased pyroptosis-associated inflammatory cytokines IL-1β and IL-18, along with Caspase-1 activity. Furthermore, cordycepin reduced the macrophage pyroptosis rate. In conclusion, cordycepin inhibits macrophage pyroptosis by reducing XO activity, suppressing ROS production, and regulating the expression of key molecules in the NLRP3/Caspase-1/GSDMD pathway. These findings provide a strong experimental basis for the potential development of cordycepin as a novel anti-inflammatory agent."],"journal":["Frontiers in pharmacology"],"pagination":["1526616"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11868043"],"repository":["biostudies-literature"],"pubmed_title":["Cordycepin attenuates NLRP3/Caspase-1/GSDMD-mediated LPS-induced macrophage pyroptosis."],"pmcid":["PMC11868043"],"pubmed_authors":["Liu Z","Lv L","Xie Y","Huang Y","Jili M","Yang R","Luo Y","Wei J"],"additional_accession":[]},"is_claimable":false,"name":"Cordycepin attenuates NLRP3/Caspase-1/GSDMD-mediated LPS-induced macrophage pyroptosis.","description":"Pyroptosis, a form of programmed cell death driven by the NLRP3 inflammasome, is a key contributor to inflammation in various diseases. This study aimed to investigate the anti-inflammatory mechanisms of cordycepin, focusing on its role in macrophage pyroptosis. Molecular docking analysis was performed to evaluate the binding affinity of cordycepin to key pyroptosis-related proteins, including NLRP3, Caspase-1, and GSDMD. RAW264.7 cells were pre-treated with cordycepin to assess its effects on pyroptosis. Key measurements included reactive oxygen species (ROS) levels, xanthine oxidase (XO) activity, and the expression of NLRP3, Caspase-1, and GSDMD. Additionally, lactate dehydrogenase (LDH) release, interleukin (IL)-1β and IL-18 levels in the culture supernatant, and macrophage cell death rates were evaluated using Hoechst 33342/PI dual staining. The results demonstrated that cordycepin exhibits strong binding affinity for NLRP3, Caspase-1, and GSDMD. Cordycepin pre-treatment significantly reduced ROS levels and XO activity, inhibited the expression of NLRP3, cleaved-Caspase-1, and cleaved-GSDMD, and decreased pyroptosis-associated inflammatory cytokines IL-1β and IL-18, along with Caspase-1 activity. Furthermore, cordycepin reduced the macrophage pyroptosis rate. In conclusion, cordycepin inhibits macrophage pyroptosis by reducing XO activity, suppressing ROS production, and regulating the expression of key molecules in the NLRP3/Caspase-1/GSDMD pathway. These findings provide a strong experimental basis for the potential development of cordycepin as a novel anti-inflammatory agent.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025","modification":"2026-06-01T22:06:38.947Z","creation":"2025-04-04T13:46:47.241Z"},"accession":"S-EPMC11868043","cross_references":{"pubmed":["40028157"],"doi":["10.3389/fphar.2025.1526616"]}}