Sipeimine ameliorates osteoarthritis progression by suppression of NLRP3 inflammasome-mediated pyroptosis through inhibition of PI3K/AKT/NF-κB pathway: An in vitro and in vivo study

作者：Yuqin Fang, Chao Lou, Junlei Lv, Chaoyang Zhang, Z Zhu, Wei Hu, Hua Chen, Liaojun Sun, Wenhao Zheng · 发表于：Journal of Orthopaedic Translation · 年份：2024 · DOI：10.1016/j.jot.2024.04.004 · 被引用次数：32 · 研究领域：Inflammasome and immune disorders、Inflammation biomarkers and pathways、Osteomyelitis and Bone Disorders Research

Background: , has attracted considerable attention due to its exceptional anti-inflammatory, analgesic, antioxidant, and anti-cancer characteristics. However, Sip's effects on OA and its mechanism still need further research. Methods: This study utilized network pharmacology to identify initial targets for Sip. Functional associations of Sip in OA were clarified through Gene Ontology (GO) enrichment analysis, bioinformatically analyzing a list of targets. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis assessed pathways linked to Sip's therapeutic efficacy in OA. Molecular docking techniques explored Sip's binding affinity with key targets. In vitro experiments assessed Sip's impact on lipopolysaccharide (LPS)-induced pro-inflammatory factors and its protective effects on collagen-II and aggrecan degradation within the extracellular matrix (ECM). Western blotting and fluorescence analyses were conducted to determine Sip-mediated signaling pathways. Moreover, in vivo experiments using a mouse OA model validated Sip's therapeutic efficacy. Results: The results from network pharmacology revealed a total of 57 candidate targets for Sip in OA treatment. GO enrichment analysis demonstrated a robust correlation between Sip and inflammatory response, response to LPS and NF-κB-inducing kinase activity in OA. KEGG enrichment analysis highlighted the significance of NF-κB and PI3K-AKT pathways in Sip's therapeutic potential for OA. Furthermore, molecular...