ABSTRACT
Sepsis-induced acute lung injury is a common and severe complication of sepsis, for which effective treatments are currently lacking. Previous studies have demonstrated the influence of wogonin in treating acute lung injury (ALI). However, its precise mechanism of action remains unclear. To delve deeper into the mechanisms underlying wogonin's impacts in sepsis-induced acute lung injury, we established a mouse sepsis model through cecal ligation and puncture and conducted further cell experiments using lipopolysaccharide-treated MH-S and MLE-12 cells to explore wogonin's potential mechanisms of action in treating ALI. Our results revealed that wogonin significantly increased the survival rate of mice, alleviated pulmonary pathological damage and inflammatory cell infiltration, and activated the SIRT1-FOXO1 pathway. Additionally, wogonin suppressed the release of pro-inflammatory factors by M1 macrophages and induced the activation of M2 anti-inflammatory factors. Further in vitro studies confirmed that wogonin effectively inhibited M1 macrophage polarization through the activation of the SIRT1-FOXO1 pathway, thereby mitigating lung pathological changes caused by ALI. In summary, our study demonstrated that wogonin regulated macrophage M1/M2 polarization through the activation of the SIRT1-FOXO1 pathway, thereby attenuating the inflammatory response and improving pulmonary pathological changes induced by sepsis-induced ALI. This discovery provided a solid mechanistic foundation for the therapeutic use of wogonin in sepsis-induced ALI, shedding new light on potential strategies for the treatment of sepsis-induced ALI.
Subject(s)
Acute Lung Injury , Flavanones , Forkhead Box Protein O1 , Macrophages , Sepsis , Signal Transduction , Sirtuin 1 , Animals , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Acute Lung Injury/etiology , Acute Lung Injury/pathology , Sirtuin 1/metabolism , Sepsis/complications , Sepsis/drug therapy , Sepsis/metabolism , Flavanones/pharmacology , Mice , Macrophages/metabolism , Macrophages/drug effects , Macrophages/pathology , Forkhead Box Protein O1/metabolism , Signal Transduction/drug effects , Male , Mice, Inbred C57BL , Disease Models, Animal , Cell Polarity/drug effects , Macrophage Activation/drug effectsABSTRACT
The original double auction studies of supply and demand markets established their strong efficiency and equilibrium convergence behavior using economically unsophisticated and untrained subjects. The results were unexpected because all individual costs and values were private and dependent entirely on the market trading process to aggregate the dispersed information into socially desirable outcomes. The exchange environment, however, corresponded to that of perishable, and not re-traded goods in which participants were specialized as buyers or sellers. We report experiments in repeated single-period markets where tradability, and buyer-seller role specialization, is varied by imposing or relaxing a restriction on re-trade within each period. In re-trade markets scope is given to speculative motives unavailable where goods perish on purchase. We observe greatly increased trade volume and decreased efficiency but subject experience increases efficiency. Observed speculation slows convergence by impeding the process whereby individuals learn from the market whether their private circumstances lead them to specialize as buyers or sellers.
