Hanchuan Zupa Granules attenuate host inflammatory and redox dysregulation in a pretreatment model of Pseudomonas aeruginosa-triggered acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE Acute infectious lung injury involves excessive innate inflammation, oxidative stress, and epithelial barrier damage. Hanchuan Zupa Granules (HCZP), a Uyghur patent medicine, are traditionally used for cold-type Nazla characterized by cough, dyspnea, and viscous sputum.

Aim

OF THE STUDY To evaluate the pretreatment-associated protective effects of HCZP on host injury responses in a Pseudomonas aeruginosa-triggered acute lung injury model and to explore related pathway-associated readouts and traceable constituents.

Materials And Methods

Kunming mice received HCZP pretreatment (0.72-2.88 g/kg, gavage) before P. aeruginosa challenge; dexamethasone served as a pharmacological comparator. BALF protein leakage, lung histology, and pathway-associated readouts were assessed at 24 h. LPS-stressed A549 cells treated with HCZP-medicated serum were used as a controlled epithelial support model. Public scRNA-seq data (GSE276682), LC-MS profiling, docking, and constituent validation were integrated as systematic pathway-associated and constituent-oriented analyses.

Results

HCZP pretreatment reduced BALF protein leakage, lung structural damage, and mucus hypersecretion, accompanied by lower IL-1β/TNF-α expression, moderated TLR4/NF-κB and PI3K/Akt signaling, enhanced Nrf2-associated antioxidant responses, and reduced apoptosis-related readouts. HCZP-medicated serum lowered ROS, restored GSH, and reduced PI-positive A549 cell death. Public scRNA-seq analysis highlighted neutrophil/myeloid remodeling in an LPS context. LC-MS prioritized liquiritin and apigenin as candidate traceable constituents with supportive in vitro epithelial activity

Conclusions

HCZP attenuated inflammation- and redox-related lung injury in P. aeruginosa-challenged mice, while liquiritin and apigenin were prioritized as candidate traceable constituents with supportive in vitro epithelial activity.