<p>Hongjingtian Injection Inhibits Proliferation and Migration and Promotes Apoptosis in High Glucose-Induced Vascular Smooth Muscle Cells</p>

Abstract

BackgroundHongjingtian injection (HJT) is administered in the treatment of vascular diseases, including diabetic angiopathies (DA). However, its underlying mechanisms have not been examined systematically.MethodsIn this research, we explored potential mechanisms of HJT through network pharmacology. HG-stimulated A7r5 cells served as the cell model. Cell proliferation, migration and apoptosis were investigated. The effects on key targets and the AKT pathway were verified by Western blotting in experiments with the AKT inhibitor LY294002 or activator SC79.ResultsNetwork analysis predicted that HJT targeted 10 candidate targets and 15 pathways including cell proliferation, migration and apoptosis in response to DA. Functional experiments showed that HJT markedly suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs, which validated the prediction. Mechanistically, HJT significantly downregulated the expression of pAKT, MMP9, and PCNA, upregulated the expression of p53 and cleaved caspase-3 and increased the Bax/Bcl-2 ratio compared with the HG group. SC79, an AKT activator, partially reversed the inhibitory effects of HJT on HG-induced VSMCs, confirming the involvement of the AKT pathway. Furthermore, the presence of the AKT inhibitor LY294002 had a similar inhibitory effect as HJT.ConclusionThese findings systematically evaluate the potential mechanisms of HJT for the treatment of DA. HJT suppressed the proliferation and migration and promoted the apoptosis of HG-induced VSMCs partly by inhibiting the AKT pathway. Additionally, this study may provide a quick and effective way to investigate the molecular mechanisms of traditional Chinese medicine.

Molecular Mechanism of Naringenin Against High-Glucose-Induced Vascular Smooth Muscle Cells Proliferation and Migration Based on Network Pharmacology and Transcriptomic Analyses

“…VSMCs could undergo phenotypic transformation and increase their ability to migrate and proliferate through upregulation of the ERK1/2 and PI3K/Akt signaling pathways stimulated by high glucose ( Shi et al, 2015 ). In a similar study, Fan et al showed that the injection of hong jing tian could improve proliferation and migration by inhibiting the Akt pathway in high-glucose-induced vascular smooth muscle cells ( Fan et al, 2019 ). In addition, Zhou et al found that arctiin could attenuate the proliferation and arrest the cell cycle in the G0/G1 phase by inactivating VEGF and the PI3K/Akt signaling pathway in high-glucose-induced human retinal capillary endothelial cells ( Zhou et al, 2020 ).…”

The X box binding protein 1/C/EBP homologous protein pathway induces apoptosis of endothelial cells under hyperglycemia

“…Fibrin deposition is inhibited by the released inflammatory factors to suppress the fibrinolytic system, which contributes to the formation of the prethrombotic state (27). High glucose concentration-induced ERS results in the dysfunction of endothelial cells, the inhibition of cell proliferation and cell death, thereby contributing to injury to vessels and various vascular diseases, including diabetic vascular disease (28,29). Autophagy, apoptosis, inflammation and senescence of endothelial cells can be induced by high dosage of glucose (30).…”

Influence of DNA Methylation on Vascular Smooth Muscle Cell Phenotypic Switching

“…Type 2 diabetes (T2D) is associated with chronic inflammation, characterized by the production of pro-inflammatory factors like TNF-a, IL-a, FGF21, and PDGF at sites of high glucose exposure. This inflammatory response involves pathways such as PI3K/Akt and NF-kB, contributing to VSMC de-differentiation, proliferation, and migration, which can trigger the additional release of pro-inflammatory agents by the VSMCs themselves, worsening vascular dysfunction [ 67 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. Additionally, VSMCs in individuals with T2D exhibit increased expression of the antiapoptotic protein Bcl-2, leading to resistance to cell death, enhanced proliferation, and a thicker media layer [ 110 ].…”