1. Academic Validation
  2. Hongjingtian Injection Inhibits Proliferation and Migration and Promotes Apoptosis in High Glucose-Induced Vascular Smooth Muscle Cells

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

  • Drug Des Devel Ther. 2019 Dec 5;13:4115-4126. doi: 10.2147/DDDT.S220719.
Zhengyuan Fan 1 2 Congcong Guo 3 Yuhan Zhang 2 4 Jinming Yao 2 4 Lin Liao 2 4 Jianjun Dong 5
Affiliations

Affiliations

  • 1 First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250355, People's Republic of China.
  • 2 Division of Endocrinology, Department of Internal Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, People's Republic of China.
  • 3 Division of Endocrinology, Department of Internal Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, People's Republic of China.
  • 4 Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, People's Republic of China.
  • 5 Division of Endocrinology, Department of Internal Medicine, Qilu Hospital of Shandong University, Jinan 250012, People's Republic of China.
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.

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.

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.

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.

Keywords

diabetes; diabetic angiopathies; network pharmacology; traditional Chinese medicine.

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