Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy.

Abstract

OBJECTIVE:

To explore the effects of the Hedysarum multijugum Maxim.-Radix Salviae compound (Huangqi-Danshen Compound (HDC)) on oxidative capacity and cardiomyocyte apoptosis in rats with diabetic cardiomyopathy by a network pharmacology-based strategy.

METHODS:

Traditional Chinese Medicine (TCM)@Taiwan, TCM Systems Pharmacology Database and Analysis Platform (TCMSP), TCM Integrated Database (TCMID), and High-Performance Liquid Chromatography (HPLC) technology were used to obtain and screen HDC's active components, and the PharmMapper database was used to predict HDC human target protein targets. The DCM genes were collected from the GeneCards and OMIM databases, and the network was constructed and analyzed by Cytoscape 3.7.1 and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, HDC was used to intervene in diabetic cardiomyopathy (DCM) model rats, and important biological processes and signaling pathways were verified using techniques such as immunohistochemistry.

RESULTS:

A total of 176 of HDC's active components and 442 potential targets were obtained. The results of network analysis show that HDC can regulate DCM-related biological processes (such as negative regulation of the apoptotic process, response to hypoxia, the steroid hormone-mediated signaling pathway, cellular iron ion homeostasis, and positive regulation of phosphatidylinositol 3-kinase signaling) and signaling pathways (such as the HIF-1 signaling pathway, the estrogen signaling pathway, insulin resistance, the PPAR signaling pathway, the VEGF signaling pathway, and the PI3K-Akt signaling pathway). Animal experiments show that HDC can reduce fasting plasma glucose (FPG), HbA1c, and malondialdehyde (MDA) and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P < 0.05). The results of immunohistochemistry showed that HDC can regulate the protein expression of apoptosis-related signaling pathways in DCM rats (P < 0.05).

CONCLUSION:

It was initially revealed that HDC improves DCM through its antiapoptotic and anti-inflammatory effects. HDC may play a therapeutic role by improving cardiomyocyte apoptosis in DCM rats.

• Authors: Shiying Zhang, Zhiying Yuan, Huaying Wu, Weiqing Li, Liang Li, Huiyong Huang
• Journal: BioMed research international (Biomed Res Int) Vol. 2020 Pg. 8260703 ( 2020) ISSN: 2314-6141 [Electronic] United States
• PMID: 33134388 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Shiying Zhang et al.

Chemical References

• Antioxidants
• Blood Glucose
• Cardiotonic Agents
• Dietary Sugars
• Drugs, Chinese Herbal
• Glycated Hemoglobin A
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Peroxisome Proliferator-Activated Receptors
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• dan-shen root extract
• Malondialdehyde
• Huang Qi
• Glutathione Peroxidase
• Superoxide Dismutase
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects, genetics)
• Astragalus propinquus
• Blood Glucose (metabolism)
• Cardiotonic Agents (pharmacology)
• Diabetic Cardiomyopathies (drug therapy, etiology, genetics, physiopathology)
• Diet, High-Fat (adverse effects)
• Dietary Sugars (adverse effects)
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression Regulation (drug effects)
• Glutathione Peroxidase (genetics, metabolism)
• Glycated Hemoglobin (genetics, metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Male
• Malondialdehyde (antagonists & inhibitors, metabolism)
• Medicine, Chinese Traditional
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Oxidative Stress (drug effects)
• Peroxisome Proliferator-Activated Receptors (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Rats
• Rats, Wistar
• Salvia miltiorrhiza
• Signal Transduction
• Superoxide Dismutase (genetics, metabolism)
• Vascular Endothelial Growth Factor A (genetics, metabolism)