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To Explore the Mechanism of Tibetan Medicine Gaoyuan' an Capsule Improving Plateau Hypoxia Tolerance


 Background: Tibetan medicine Gaoyuan 'an capsule (GYAC) is widely used to prevent pulmonary edema at high altitude, but the specific mechanism of its action has not been explored. Therefore, based on bioinformatics and network pharmacology, this study analyzed the mechanism of improving hypoxia tolerance of GYAC, and provided new ideas for the prevention of altitude disease.Methods: The effective components and corresponding targets of GYAC were screened by using the Chinese herbal medicine network database, and the key targets of diseases were retrieved by using Genecards, OMIM and PubMed database with the key word "hypoxia". The drug targets and disease targets were mapped into common targets to obtain the final target. Cytoscape 3.7.2 was used to analyze the topological network and construct the Herbs-Components-Targets network and Core Targets-Signal Pathways network. GO function and KEGG enrichment analysis were performed to predict the mechanism of action, and molecular docking techniques were used to verify the binding force of target compounds and targets.Results: The results showed that GYAC enhanced hypoxia tolerance by simultaneously regulating the functions of various signaling proteins, including IL6、TNF、NOS3、VEGFA etc. The main regulatory pathways were HIF-1 signaling pathway, Chagas disease, and pathway in cancer. The main biological processes involved are the positive regulation of RNA polymerase II promoter transcription, the extracellular space as the cell component, and the cytokine activity as the molecular function. Molecular docking shows that hydrogen bonding is the main form of binding between drug molecules and proteins.Conclusions: GYAC is mainly directed at the interaction of HIF-1 signaling pathway with targets such as IL6 and TNF to improve the body's hypoxia tolerance, that is, they are multi-pathway, multi-pathway and multi-target interaction.