Astragaloside IV reduces lung injury in lethal sepsis via promoting treg cells expansion and inhibiting inflammatory responses.

ABSTRACT

Sepsis is a systemic inflammatory response syndrome caused by an infection progressing to sepsis-associated organ failure (such as lung injury). Our previous review revealed that Astragaloside IV (ASI-IV), one of the primary bioactive ingredients in Astragalus membranaceus (Fisch) Bge (Huang-Qi), had been shown to exert anti-inflammatory and immunomodulatory effects. Nevertheless, it is still unclear whether ASI-IV could attenuate septic lung injury via activating regulatory T-cells (Tregs). This study was designed to evaluate the therapeutic potential of ASI-IV on sepsis-induced lung injury and to further explore its underlying mechanism. In the murine models of cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) induced sepsis, ASI-IV can markedly improve the survival rate and reduce inflammatory lung injury, protect mice against exacerbated inflammatory responses by decreasing myeloid cell infiltration and down-regulating IL-6 and TNF-α in lung tissue. Meanwhile, Treg cell-related gene expression, including Foxp3 and IL-10, significantly increased after ASI-IV treatment. Furthermore, ASI-IV notably promoted the differentiation of naïve CD4+ T cells into T regulatory cells without obviously affecting Th1 and Th17 differentiation. Our results indicated that ASI-IV could attenuate septic lung injury by promoting Treg cell expansion and inhibiting inflammatory responses. It represents a promising agent for the treatment of sepsis.