Exploring the mechanism of action of Hypoglycaemic Shuxin Formula in the treatment of diabetes mellitus combined with chronic heart failure based on network pharmacology and experimental validation
Abstract
The purpose of this paper is to investigate the mechanism of action of traditional Chinese medicine (TCM)compound hypoglycemic Shuxin formula in the treatment of diabetes mellitus(DM) combined with chronic heart failure(CHF) through network pharmacology methods and experimental verification. Methods: The network pharmacology database and related platforms were applied to retrieve the active ingredients of Jiang Tang Shu Xin Recipe(JTSX) and the targets related to diabetes mellitus combined with chronic heart failure.The PPI protein interaction network and compound drug-ingredient-target network were constructed. Molecular docking was performed to verify the affinity. DM and CHF rat models were established, HE staining was performed, and the levels ofC-reactive protein (CRP), tumor necrosis factor alpha (TNF -α), and interleukin-6 (IL-6) in rat serum were detected using ELISA, and the levels of TNF-α and IL-6 in myocardial tissues were detected by immunohistochemistry. Western blot method was used to verify the therapeutic efficacy of the network’s core pharmacological targets. Results: A total of 171 active ingredients, 331 intersecting targets, and 196 signaling pathways were retrieved. The core components are: 1-dimethyl-2,3- dihydrophenanthren-4-one, kaempferol, miltionone Ⅰ,Ginsenoside-Rh4, 3,9-di-O-methylnissolin,5,6-dihydroxy-7-isopropyl-1. The core targets are tyrosine kinase (SRC), epidermal growth factor (EGFR), serine/threonine protein kinase (AKT1),insulin (INS), and tumor necrosis factor (TNF).The molecular docking results show that there is a good binding ability between the core components and the core targets. The results of animal experiments hanve shown that: hypoglycemic Shuxin Fang can improve the degree of myocardial fibrosis, reduce the level of TNF-α, IL-6 in myocardial tissue and the expression of key protein AKT1 in myocardial tissue. Conclusion: JTSX treats diabetes mellitus combined with chronic heart failure through multi-components and multi-targets, and exerts anti-fibrotic effect on myocardial tissues.
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