Background: The incidence of altitude-related diseases has increased as more and more people have begun living in places at high altitudes. High-altitude polycythemia (HAPC) is a very widespread disease in high-altitude areas. Salvia miltiorrhiza has high medicinal value, with anti-tumor, anti-inflammatory, anti-myocardial ischemia, anti-oxidative stress, anti-thrombosis, and vascular dilation effects, as well as anti-atherosclerosis effects, thereby protecting against brain tissue damage, improving microcirculation, and activating the immune system. This study aimed to predict the latent molecular mechanisms through which the main active ingredients of Salvia miltiorrhiza treat HAPC disease using bioinformatics methods, including network pharmacology and molecular docking. Methods: The Traditional Chinese medicine system pharmacology (TCMSP) database was used to screen for effective compounds and protein targets of Danshen, and the chemical structures of these compounds were downloaded. Using ‘high-altitude polycythemia’ as the keyword, the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases were searched for potential disease targets, and the overlapping targets were identified through an intersection analysis. The protein-protein interaction (PPI) network was analyzed using Cytoscape 3.80. The Metascape database was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. 3D structures of the major proteins were obtained from the Protein Data Bank (PDB) database, and molecular docking was conducted between the main compounds and the core proteins, after which binding energies were plotted as a heatmap. The binding scenarios of the top two binding energies were visualized. Results: Danshen has anti-HAPC effects on the major compounds MOL000006, MOL007154, MOL007145, MOL007100, MOL007041, MOL007049, MOL007108, and MOL007088; the core targets are RAC-alpha serine/threonine-protein kinase (AKT1), interleukin-6 (IL6), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-9 (MMP9), nitric oxide synthase 3 (NOS3), estrogen receptor (ESR1), peroxisome proliferator-activated receptor gamma (PPARG), and interleukin-10 (IL10). The GO and KEGG results revealed that Danshen may exert anti-HAPC activity by regulating the binding of ligand-activated transcription factors, nuclear receptor activity, signaling receptor regulator activity, and the binding of certain other molecules to cellular compounds such as receptor complexes, the side of the membrane, the endoplasmic reticulum lumen, and the response to hormones, thereby achieving the regulation of epithelial cell migration, blood pressure, and other biological process (BP) entries. The signaling pathways related to the mechanism of action of Danshen mainly include the cancer pathway, the Hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the Phosphatidyqinositol-3 kinase-RAC-alpha serine/threonine-protein kinase (PI3K-Akt) signaling pathway. The molecular docking results showed that the active components bound more stably to the targets, especially NOS3, TNF, and AKT1. Conclusion: This research predicted the primary active compounds, targets of action, and signaling pathways involved in predicting the efficacy of Danshen in treating HAPC, using network pharmacology and molecular docking methods. This research provides the theoretical basis for subsequent experimental studies on the use of Danshen in clinical practice.
Ren et al. (2026) studied this question.