Single-cell transcriptomics and metabolomics demonstrate that Taohe Chengqi decoction alleviates sepsis-associated acute lung injury by modulating immunometabolism.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical treatment of sepsis-associated acute lung injury (SA-ALI) is a major issue faced by critical care medicine. Taohe Chengqi decoction (THCQ), a formulation rooted in traditional Chinese medicine, exhibits potential therapeutic efficacy in the management of sepsis-associated complications. However, the precise mechanisms underlying its effects remain to be comprehensively elucidated. AIM OF THE STUDY: This study aimed to explore the potential immunometabolism mechanisms of THCQ in the treatment of SA-ALI. MATERIALS AND METHODS: The study first established an LPS-induced SA-ALI mouse model to verify the pharmacological effects of THCQ. Non-targeted metabolomics was employed to explore the metabolic pathways regulated by THCQ, including OPLS-DA, differential metabolites, and pathway enrichment. Single-cell transcriptomics was employed to investigate the immune microenvironment regulated by THCQ, including gene expression analysis, pathway enrichment, and cellular communication. Finally, the pharmacological mechanism of THCQ was validated by Western blotting, RT-PCR, ELISA, and flow cytometry. RESULTS: Integrating single-cell transcriptomics and untargeted metabolomics analysis revealed that THCQ improved the alveolar-capillary barrier by inhibiting glycolysis. Specifically, THCQ ameliorated pathological changes in alveolar epithelial cells and microvascular endothelial cells, and inhibited the pro-inflammatory response of damage-responsive alveolar fibroblasts. THCQ reversed the pathological mechanism of Il1balveolar macrophages and NK cells by regulating glycolysis, and demonstrated the potential to regulate the phenotype of Fth1neutrophils and Prok2neutrophils, reshaping the immune microenvironment during SA-ALI. CONCLUSION: This study reveals the immunometabolism mechanism of THCQ treatment for SA-ALI through single-cell transcriptomics and metabolomics analysis, laying the groundwork for subsequent fundamental research and clinical applications. These findings are based on one batch of THCQ, so further studies are necessary to confirm consistent effects across multiple batches for reproducibility and clinical relevance.