Ligustrum lucidum polysaccharide ameliorated immune mediated inflammatory responses by regulating both the cGAS STING pathway and the inflammasome

Background Fructus Ligustri Lucidi is recognized as a functional food with hepatoprotective effects, and as a derivative of this well known food and medicine homology herb, Ligustrum lucidum polysaccharide exhibits potent anti inflammatory and antioxidant biological activities. In recent years, mounting evidence has shown that abnormal activation of the cGAS-STING signaling pathway mediated by the cytosolic DNA sensor cGAS, and the inflammasome signaling pathway mediated by various cytosolic sensors, contributes significantly to the development. Therefore, it is crucial to investigate LLP as a potential nutraceutical candidate derived from a food and medicine homology resource that can specifically downregulate these pathogenic pathways for therapeutic intervention. Methods Pretreatment with LLP was followed by the analysis of type I IFN-related genes, pro-inflammatory cytokines such as IL-1β, and the expression levels of associated proteins. Furthermore, the impact of LLP on downstream signaling events was examined. In parallel, ConA-induced autoimmune hepatitis and CLP-induced sepsis models were established to evaluate the in vivo efficacy of LLP against cGAS-STING and inflammasome associated immune-mediated inflammatory diseases. Results LLP suppresses the cGAS-STING and inflammasome pathways by disrupting TBK1-IRF3 interaction and impeding ASC oligomerization, effectively attenuating the subsequent secretion of type I interferons and IL-1β. Consistent with its in vitro activity, LLP ameliorated pathologies in mouse models of cGAS-STING and inflammasome mediated immune diseases, including CLP-induced sepsis and ConA-induced autoimmune hepatitis. Conclusions LLP effectively suppresses cGAS-STING and inflammasome activation to ameliorate CLP-induced sepsis and ConA-induced autoimmune hepatitis, suggesting its broad utility in treating immune-mediated inflammatory diseases.