Bioinformatics and network pharmacology to explore Huangqi Guizhi Wuwu Decoction in regulating mitophagy to ameliorate doxorubicin-induced cardiotoxicity the potential mechanism
Abstract
While studies suggested that Huangqi Guizhi Wuwu Decoction (HGWD) can mitigate doxorubicin-induced cardiotoxicity (DIC), the specific mechanism of action remains unclear. GSE106297, GSE157282, and GSE206803 were downloaded to screen for differentially expressed genes (DEGs), followed by gene set enrichment analysis and immune infiltration analysis. DIC-related genes were obtained by the intersection of weighted gene co-expression network analysis and DEGs. The active ingredients and target genes of HGWD were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform database, and HGWD-DIC common targets were identified by intersecting them with DIC-related genes. A drug-active ingredient-target network was constructed to select the core components of HGWD. Mitophagy-related genes were obtained from GeneCards, PHARMGKB, and OMIM databases, and intersecting them with common targets yielded the core genes, which were then subjected to enrichment analyses. A protein-protein interaction network was constructed to identify key genes, further assessing their diagnostic value. The effect of HGWD on the expression of key genes was further validated using prepared medicated serum. The interactions between the core components and key genes were validated through molecular docking and molecular dynamics simulation. A total of 2344 DEGs were identified, with gene set enrichment analysis results primarily enriched in categories such as apoptosis, p53…
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