Glycyrrhizic acid alleviates lung injury in sepsis through SIRT1/HMGB1 pathway

Objectives:This study explores the protective effects of glycyrrhizic acid(GA)on sepsis-induced cellular damage and inflammation in acute lung injury(ALI),specifically through the modulation of the sirtuin 1(SIRT1)and high mobility group box 1(HMGB1)pathway.Methods:The study employed two experimental models:lipopolysaccharide(LPS)-induced BEAS-2B human lung epithelial cells and cecal ligation and puncture(CLP)rats,to simulate sepsis conditions.The cell model involved treatments with LPS,GA,control siRNA(si-NC),and SIRT1-specific siRNA(si-SIRT1).Evaluations included cell viability,apoptosis,and cytokine production.In the rat model,treatments included GA and the SIRT1 inhibitor EX527,with assessments on lung tissue damage,inflammation,and protein expression using Western blot and co-immunoprecipitation(Co-IP)analysis.Results:LPS exposure significantly reduced SIRT1 mRNA levels and cell viability in BEAS-2B cells,which effects were reversed by cotreatment with GA and si-NC but negated by si-SIRT1.LPS also induced apoptosis and increased pro-inflammatory cytokines and HMGB1 expression,which were mitigated by GA and si-NC and exacerbated by si-SIRT1.In CLP rats,GA treatment decreased lung tissue damage,inflammatory cytokines,and HMGB1 expression,and enhanced SIRT1 levels.However,these protective effects were reversed when GA was combined with EX527.Conclusion:GA demonstrates significant protective effects against LPS-induced damage and inflammation in lung cells and tissue by modulating the SIRT1-HMGB1 pathway.This suggests that GA could be a potential therapeutic strategy for treating sepsis and related inflammatory conditions.