Herbal-based Xuebijing injection ameliorated vascular endothelial dysfunction in sepsis-associated lung injury via inhibiting ACLY/MYB/RIG-I axis

Excessive endothelial pro-inflammatory response is an early hallmark in sepsis-induced acute lung injury (ALI). Xuebijing (XBJ) as a Chinese traditional medicine is widely used for treating sepsis in the clinic. However, the molecular mechanism of the beneficial effectiveness of XBJ remains unclear. Our present study showed that XBJ inhibited phosphorylation-dependent activation of ATP citrate lyase (ACLY), thereby suppressing the acetylation-dependent nuclear translocation of transcription factor MYB. Thus, as the downstream target gene of MYB, the expression of retinoic acid inducible gene I (RIG-I) was downregulated, leading to the inhibition of NF-κB signaling and EC pro-inflammatory and coagulation activation, which further alleviated sepsis-associated ALI. Moreover, XBJ compounds Quercetin, Ferulic Acid, Kaempferol and Paeoniflorin all showed inhibitory effects on the activation of the downstream MYB/RIG-I signaling by binding to ACLY protein. Our study revealed the novel regulatory mechanism of XBJ in sepsis-induced EC dysfunction and ALI via ACLY/MYB/RIG-I axis, providing theoretical basis for the clinical application of XBJ and shedding insight into novel therapeutic targets for treating sepsis.