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

Authors Fan Z, Guo C, Zhang Y, Yao J, Liao L, Dong J

Received 25 June 2019

Accepted for publication 12 November 2019

Published 5 December 2019 Volume 2019:13 Pages 4115—4126

DOI https://doi.org/10.2147/DDDT.S220719

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Qiongyu Guo


Zhengyuan Fan,1,2 Congcong Guo,3 Yuhan Zhang,2,4 Jinming Yao,2,4 Lin Liao,2,4 Jianjun Dong5

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

Correspondence: Lin Liao; Jianjun Dong
Division of Endocrinology, Department of Internal Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, People’s Republic of China
Tel +86-15168888260; +86-13791122910
Email liaolin@sdu.edu.cn; cwc_ll@sdu.edu.cn

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: network pharmacology, diabetic angiopathies, traditional Chinese medicine, diabetes
 

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