Systematically investigating the pharmacological mechanism of Dazhu Hongjingtian in the prevention and treatment of acute mountain sickness by integrating UPLC/Q-TOF-MS/MS analysis and network pharmacology

Abstract

Members of the genus Rhodiola L. have been widely used in Tibetan medicines for preventing and treating acute mountain sickness (AMS) for a long time. However, the pharmacological mechanisms of these medicines in treating AMS remain unclear. To address this problem, an integrative method combining ultra-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS)analysis and network pharmacology was employed. First, the chemical profiles of Dazhu Hongjingtian (DZ, a Chinese medicine preparation composed of R. kirilowii (Regel) Maxim) were identified or tentatively characterized. Second, the targets of DZ were predicted using the SwissTargetPrediction and STITCH databases; the targets of AMS were also collected from the Drugbank and TTD databases. Then, networks between targets and compounds or diseases were constructed by Cytoscape 3.6.1. Third, GO and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 40 ingredients of 53 compounds in DZ might be biologically active. These activities were related to the regulatory effects of the ingredients on 68 significant signaling pathways, such as the inflammation pathway, apoptosis pathway, HIF-1 signaling pathway, and others, by targeting 33 proteins, including PTGS2 and PTGS1, ALOX5 and ALOX15, BCL2 and BCL2L1, the protein kinase C (PKC) family and HIF1A, among others.