JMDSJournal of Medicines Development Sciences2382-63632382-6371Bio-Byword Scientific Publishing Pty. Ltd.10.26689/JMDS.v11i3.16019ArticleThe Effect of Muscone on Lipopolysaccharide-Induced Damage to Human Umbilical Vein Endothelial Cellshttps://artdesignp.com/journal/JMDS/11/3/10.26689/JMDS.v11i3.16019LiMiao20261132026-09-16Objective: To investigate the role and mechanism by which musk ketone modulates the NLRP3/Caspase-1/GSDMD signaling pathway to intervene in lipopolysaccharide (LPS)-induced pyroptosis in human umbilical vein endothelial cells (HUVECs). Methods: The CCK-8 assay was used to screen for the safe and effective concentration of musk ketone. HUVECs were divided into a control group, a model group, and low-, medium-, and high-dose musk ketone groups. A pyroptosis model was established by stimulating cells with 10 μg/mL LPS for 16 h, and each dose group was treated with musk ketone for 24 h. The NO level, inflammatory cytokine expression, and protein levels in the pyroptosis pathway were assessed using an NO assay kit, ELISA, and Western blot, respectively. Results: Musk ketone at concentrations ranging from 1 to 75 μmol/L exhibited no significant cytotoxicity. NO measurements revealed that NO levels in the cell supernatant were significantly higher in the model group compared to the control group. Additionally, Western blot analysis showed that the expression levels of NLRP3, Caspase-1, and GSDMD proteins were elevated in the model group compared to the control group, collectively confirming that LPS successfully induced pyroptosis and inflammatory damage in endothelial cells. ELISA results showed that the expression levels of IL-18 and IL-1β in the model group were significantly higher than those in the control group (P < 0.05); compared with the model group, the high-, medium-, and low-concentration muskon groups all showed a significant reduction in IL-18 expression in cells (P < 0.05); compared with the model group, the high- and low-concentration muskon groups both showed a significant reduction in IL-1β expression in cells (P < 0.05). Western blot results showed that, compared with the control group, the model group exhibited increased expression of NLRP3, Caspase-1, and GSDMD proteins in cells (P < 0.01). Compared with the model group, the high-, medium-, and low-dose muscone groups all exhibited significantly reduced expression of NLRP3, Caspase-1, and GSDMD proteins in cells (P < 0.05). Conclusion: Musk ketone can effectively inhibit LPS-induced pyroptosis in human umbilical vein endothelial cells and suppress cellular inflammatory damage by inhibiting the NLRP3/Caspase-1/GSDMD signaling pathway and reducing the release of inflammatory factors.Muscone, Pyroptosis, NLRP3/GSDMD/Caspase-1, Inflammatory factors

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