DefinePK

Abstract

Background and Objective: Low air pressure and hypoxia conditions at high altitudes adversely affect the respiratory, circulatory and nervous systems, which in turn accelerates the onset and progression of chronic kidney disease. Recent studies have shown the protective effect of verbascoside (VB) against kidney injury due to its antioxidant properties. However, the pharmacologic mechanism of VB on high-altitude renal disease remains unclear. Hence, the objective of this study was to explore the key targets and possible molecular mechanisms of VB against high-altitude renal disease through network pharmacology, molecular docking and in vitro experiments. Materials and Methods: Targets of VB, high-altitude renal disease and hypoxia-induced pathways were obtained. Venn diagram identified key targets. The GO and KEGG analyses revealed of VB involvement in biological processes and pathways in high-altitude renal disease. Molecular docking studied of VB binding interactions with hub genes. The CCK-8 and qRT-PCR assessed cell viability and mRNA expression of EGLN1, HMOX1 and BCL-2 in hypoxia-induced HK-2 cells. Results: The EGLN1, HMOX1 and BCL-2 were identified as VB target genes against high-altitude renal disease. The VB directly interacted with them in the HIF-1 signaling pathway. The miR-409-3p and miR-495-3p might regulate these genes. The VB significantly increased HK-2 cell viability and decreased mRNA levels of EGLN1, HMOX1 and BCL-2. Conclusion: Under hypoxic conditions, VB potentially treats high-altitude renal disease by downregulating EGLN1, HMOX1 and BCL-2 mRNA expression, contributing to improved renal function and disease progression delay in high-altitude renal disease.