XueBiJing injection improves the symptoms of sepsis-induced acute lung injury by mitigating oxidative stress and ferroptosis

Ethnopharmacological relevance: XBJ injection is approved by the China Food and Drug Administration for the adjunctive treatment of sepsis, and it is derived from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It consists of five Chinese herbal extracts: Carthamus tinctorius, Paeonia lactiflora, Salvia miltiorrhiza, Conioselinum anthriscoides 'Chuanxiong' and Angelica sinensis.

Aim of the study: The purpose of this study was to explore the relationship between Ferroptosis and acute septic lung injury, and to evaluate the improvement effect of XBJ injection on acute lung injury in sepsis.

Materials and methods: Acute lung injury was induced in rats by cecum ligation and puncture, and these rats were treated with XBJ injection. Oxidative stress and inflammation levels were assessed in serum and lung tissue, and tissue samples were collected for histological and protein analyses. To illustrate the mechanism of the improvement effect of XBJ on acute lung injury in sepsis, serum lipidomics was carried out to investigate whether XBJ prevents oxidative stress-induced lipid metabolism disorders. Furthermore, protein expression of ferroptosis-related genes was also examined.

Results: XBJ was shown to be effective in alleviating sepsis-induced ALI. XBJ also improves sepsis-induced acute lung injury by reducing lipid peroxidation and inflammation and modulating Ferroptosis pathways. Specifically, compared with the sham group, XBJ downregulated the levels of Fe²⁺, MDA and GSSG, and reversed the decrease in the levels of GSH and GSH/GSSH in lung tissue. Metabolic pathways such as glycerophospholipid metabolism, phospholipid metabolism, and lipid metabolism associated with Ferroptosis were obtained by lipidomic analysis of differential lipid metabolite enrichment, suggesting that Ferroptosis occurs in septic rats, and that XBJ inhibits Ferroptosis and thereby improves sepsis-induced ALI. Furthermore, XBJ optimises iron metabolism and lipid oxide metabolism by regulating the expression of a series of proteins that are closely related to Ferroptosis, such as GPX4, ACSL4, x-CT, and FTH1.

Conclusions: Our findings, initially, indicated that XBJ ameliorates sepsis-induced ALI by reducing oxidative stress and Ferroptosis, revealing a previously unrecognised mechanism by which XBJ ameliorates sepsis-induced ALI.

Acute lung injury; Ferroptosis; Oxidative stress; Sepsis; Xuebijing injections.