Acute lung injury (ALI), a life-threatening syndrome characterized by diffuse alveolar damage, pulmonary edema, and acute respiratory failure, is often triggered by infections or trauma and can progress to severe acute respiratory distress syndrome (ARDS) with high mortality. Currently, there are no specific clinical drugs for ALI, making the development of effective therapeutic strategies an urgent clinical need.
A research team led by Prof. Chengpeng Sun and Prof. Juan Zhang from Tianjin University of Traditional Chinese Medicine, collaborated with Tianjin Chasesun Pharmaceutical Co., Ltd., systematically explored the therapeutic effects and molecular mechanisms of Xuebijing injection (XBJ) in ALI. XBJ, composed of five traditional Chinese medicines, has long been used clinically for respiratory infections, but its precise mechanism in ALI remained unclear.
Using LPS-induced ALI mouse models and MH-S alveolar macrophage models, the team demonstrated that XBJ significantly alleviated lung pathological damage, reduced infiltration of macrophages and neutrophils, and lowered levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and tissue damage markers (MPO, LDH). It also restored alveolar barrier integrity by upregulating tight junction proteins (occludin, claudin-1) and rebalanced the immune system by regulating Treg/Th17 cell subsets.
Mechanistically, XBJ exerted dual regulatory effects by inhibiting both inflammatory responses and ferroptosis. It suppressed the activation of MAPK, NF-κB, and NLRP3 inflammasome pathways, which are key drivers of ALI inflammation. Meanwhile, XBJ regulated iron metabolism and antioxidant defense, upregulating anti-ferroptotic proteins (GPX4, Slc7a11, FPN1) and downregulating ferroptosis-promoting markers (TFRC, DMT1), thereby reducing lipid peroxidation and iron overload.
Using integrated chemical biology approaches (affinity pull-down, CETSA, DARTS), the team identified five direct intracellular targets of XBJ: pyruvate kinase M2 (PKM2), enolase 1 (ENO1), PDZ binding kinase (PBK), eukaryotic translation initiation factor 3i (EIF3I), and kelch-like ECH-associated protein 1 (Keap1). Further molecular docking showed that key bioactive components of XBJ (oleic acid, ethyl 4-hydroxy-3-methoxycinnamate, etc.) could specifically bind to these targets, explaining its multi-target synergistic mechanism.
As a clinically approved formulation, XBJ has mature safety and pharmacokinetic data, greatly facilitating its clinical translation. This study not only clarifies the molecular mechanism of XBJ in ALI treatment but also provides a new multi-target therapeutic strategy for this intractable disease.
This work entitled “Xuebijing injection ameliorates LPS-mediated acute lung injury via multi-target synergy by alleviating inflammation and ferroptosis” was published online in Targetome on February 9, 2026.
DOI:10.48130/targetome-0026-0005