Dan-Shen-Yin Granules Prevent Hypoxia-Induced Pulmonary Hypertension via STAT3/HIF-1α/VEGF and FAK/AKT Signaling Pathways

Abstract

Traditional Chinese medicine (TCM) plays an important role in the treatment of complex diseases, especially cardiovascular diseases. However, it is hard to identify their modes of action on account of their multiple components. The present study aims to evaluate the effects of Dan-Shen-Yin (DSY) granules on hypoxia-induced pulmonary hypertension (HPH), and then to decipher the molecular mechanisms of DSY. Systematic pharmacology was employed to identify the targets of DSY on HPH. Furthermore, core genes were identified by constructing a protein-protein interaction (PPI) network and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analysis. Related genes and pathways were verified using a hypoxia-induced mouse model and hypoxia-treated pulmonary artery cells. Based on network pharmacology, 147 potential targets of DSY on HPH were found, constructing a PPI network, and 13 hub genes were predicted. The results showed that the effect of DSY may be closely associated with AKT serine/threonine kinase 1 (AKT1), signal transducer and activator of transcription 3 (STAT3), and HIF-1 signaling pathways, as well as biological processes such as cell proliferation. Consistent with network pharmacology analysis, experiments in vivo demonstrated that DSY could prevent the development of HPH in a hypoxia-induced mouse model and alleviate pulmonary vascular remodeling. In addition, inhibition of STAT3/HIF-1α/VEGF and FAK/AKT signaling pathways might serve as mechanisms. Taken together, the network pharmacology analysis suggested that DSY exhibited therapeutic effects through multiple targets in the treatment of HPH. The inferences were initially confirmed by subsequent in vivo and in vitro studies. This study provides a novel perspective for studying the relevance of TCM and disease processes and illustrates the advantage of this approach and the multitargeted anti-HPH effect of DSY.

Deciphering the Efficacy and Mechanism of Astragalus membranaceus on High Altitude Polycythemia by Integrating Network Pharmacology and In Vivo Experiments

“…The qRT-PCR results indicated that AM decreased the hypoxia-induced HIF-1α mRNA expression ( p < 0.05). AKT-1 was a major regulator of HIF-1α [ 30 ], and AM declined AKT-1 mRNA expression ( p < 0.01). As illustrated in Figure 11 , HMOX1, NOS2, NOS3, EPO, VEGFA, and SERPONE1 were all downstream molecules of the HIF-1 signaling pathway.…”

Exploration of the Pharmacological Mechanism of Bufei Nashen Pill in Treating Chronic Obstructive Pulmonary Disease Using Network Pharmacology Integrated Molecular Docking

“…Dan Shen aims to remove blood stasis and promote blood circulation, and is widely used in clinical practice for the treatment of cardiovascular diseases, and severe pulmonary bloating. 33 The whole prescription can reduce symptoms and improve pulmonary function, and lower the risk of exacerbations for patients with COPD. 9 According to the results of network pharmacology, there are 172 components in BFNSP.…”

Expression profiles of circRNAs and identification of hsa_circ_0007608 and hsa_circ_0064656 as potential biomarkers for COPD-PH patients

“…Bioinformatics tools has been widely applied in oncology to identify genetic changes and new potential biomarkers associated with various diseases [14][15][16] . Likewise, researchers have tried to apply bioinformtics analysis in the study of PH to to elucidate the potential functions of circRNAs related to PH, mostly based on databases and animal experiments [17][18][19][20][21][22][23][24][25][26] . However, few studies have utilized clinical samples with definite diagnosis of PH, and researches for PH in COPD are even fewer.…”