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Hongjingtian Injection Inhibits Proliferation and Migration and Promotes Apoptosis in High Glucose-Induced Vascular Smooth Muscle Cells.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2019 Dec 05; Vol. 13, pp. 4115-4126. Date of Electronic Publication: 2019 Dec 05 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- Background: Hongjingtian injection (HJT) is administered in the treatment of vascular diseases, including diabetic angiopathies (DA). However, its underlying mechanisms have not been examined systematically.<br />Methods: In 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.<br />Results: Network 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.<br />Conclusion: These 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.<br />Competing Interests: The authors report no conflicts of interest in this work.<br /> (© 2019 Fan et al.)
- Subjects :
- Animals
Cell Movement drug effects
Cell Proliferation drug effects
Cells, Cultured
Diabetic Angiopathies drug therapy
Diabetic Angiopathies pathology
Dose-Response Relationship, Drug
Drugs, Chinese Herbal administration & dosage
Glucose pharmacology
Molecular Structure
Rats
Structure-Activity Relationship
Apoptosis drug effects
Drugs, Chinese Herbal pharmacology
Glucose antagonists & inhibitors
Muscle, Smooth, Vascular drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 31827318
- Full Text :
- https://doi.org/10.2147/DDDT.S220719