Mechanism of Shenqi Citian Granules in the treatment of acute mountain sickness based on proteomics and serum pharmacochemistry.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi Citian Granules (SQCT), a traditional Chinese medicine compound formula derived from Tibetan medical empirical knowledge, is composed of 15 medicinal materials including the Tibetan herb Manjing (Brassica rapa L.). It is used to treat acute mountain sickness (AMS). AIM OF STUDY: To scientifically evaluate the therapeutic efficacy of SQCT for AMS treatment and explore its underlying mechanisms, thereby bridging traditional ethnopharmacological knowledge with contemporary biomedical research. MATERIALS AND METHODS: The SQCT bioactive constituents were identified via serum pharmacochemistry and ultra-performance liquid chromatography-tandem mass spectrometry. An AMS rat model was established using a hypobaric hypoxia chamber simulating a 7000-m altitude. The primary outcome measures included loaded swimming time and blood gas parameters and biochemical indices. The blood lactate concentrations were measured using a biochemical assay kit. The inflammatory cytokine and hypoxia-inducible factor (HIF) concentrations in lung tissue were detected using ELISA kits. Morphological changes in the lung and brain tissues were observed using H&E staining. Network pharmacology, lung tissue proteomics, and Western blot analyses were conducted to explore the potential mechanisms. RESULTS: UPLC-MS/MS analysis identified 36 bioactive SQCT constituents. SQCT significantly increased the loaded swimming time of AMS rats, decreased blood lactate concentrations, improved blood gas parameters, and reduced blood biochemical indices including AST concentration. It also reduced inflammatory cytokine and HIF concentrations in the lung tissue and ameliorated inflammatory and edematous lesions in both lung and brain tissues. The network pharmacology and proteomics results implicated the HIF-1 and necroptosis signaling pathways in the therapeutic effects of SQCT on AMS. Western blot experiments confirmed downregulated expressions of key nodes in both HIF-1 and necroptosis signaling pathways by SQCT. CONCLUSION: SQCT effectively treats AMS via multi-component, multi-target mechanisms, and the HIF-1 and necroptosis signaling pathways are key targets.