Network Pharmacology and Molecular Docking Reveal the Mechanism of Tanshinone IIA against Pulmonary Hypertension

Abstract

Background: Pulmonary hypertension (PH) is a complex disease caused by a wide range of underlying conditions, Tanshinone IIA (Tan IIA) has been widely used in PH patients. The study aimed to explore the possible molecular mechanism of Tan IIA against PH by network pharmacology and molecular docking. Methods: Tan IIA and PH-related targets were retrieved from public databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) network were used to investigate the protein targets and mechanism. The binding activity of core targets and Tan IIA were verified by molecular docking. Results: A total of 26 overlapping target proteins between Tan IIA and PH were screened. PPI network identified HSP90AA1, PTPN11, ATM, CA2, TERT, PRKDC, and APEX1 as key pharmacological targets. The results of GO function enrichment analysis included regulation of smooth muscle cell proliferation and migration, regulation of mitotic cell cycle, and regulation of G1/S transition of mitotic cell cycle. KEGG pathway analysis showed that nitrogen metabolism, NF-kappa B signaling pathway, cell cycle, necroptosis, apoptosis, and JAK-STAT signaling pathway were associated with Tan IIA in PH. The molecular docking results showed that Tan IIA can closely bind three core targets (HSP90AA1, PTPN11, and CA2). Conclusions: The present work initially clarified the effective therapeutic targets, biological processes, and signaling pathways of Tan IIA treatment of PH, which lay a foundation for further research on the pharmacological effects of Tan IIA.