Exploring the Therapeutic Mechanism of Tingli Dazao Xiefei Decoction on Heart Failure Based on Network Pharmacology and Experimental Study

Dan-Dan Zhao; Xiao-Qing Zhang; Tao Yang; Qian Liu; Zhen-Zhen Lan; Xiao-Li Yang; Hui-Yan Qu; Hua Zhou

doi:10.1155/2021/6645878

Exploring the Therapeutic Mechanism of Tingli Dazao Xiefei Decoction on Heart Failure Based on Network Pharmacology and Experimental Study

Evid Based Complement Alternat Med. 2021 Nov 25:2021:6645878. doi: 10.1155/2021/6645878. eCollection 2021.

Authors

Dan-Dan Zhao¹, Xiao-Qing Zhang¹, Tao Yang¹, Qian Liu¹, Zhen-Zhen Lan¹, Xiao-Li Yang¹, Hui-Yan Qu², Hua Zhou^{1

2}

Affiliations

¹ Cardiovascular Research Institute, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
² Cardiovascular Department of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Abstract

Background: Tingli Dazao Xiefei decoction (TDXD) has been shown to have a therapeutic effect on heart failure (HF). Nevertheless, its molecular mechanism for treating HF is still unclear.

Materials and methods: TDXD and HF targets were collected from the databases, and protein-protein interaction (PPI) analysis and enrichment analysis were performed on the overlapping targets. Then, AutoDock was employed for molecular docking. Finally, we used the left anterior descending coronary artery (LAD) ligation to induce HF model rats for in vivo experiments and verified the effect and mechanism of TDXD on HF.

Results: Network pharmacological analysis showed that the main active components of TDXD in treating HF were quercetin, kaempferol, beta-carotene, isorhamnetin, and beta-sitosterol, and the core targets were IL-6, VEGFA, TNF, AKT1, and MAPK1. Multiple gene functions and signaling pathways were obtained by enrichment analysis, among which inflammation-related, PI3K/Akt, and MAPK signaling pathways were closely related to HF. Furthermore, the molecular docking results showed that the core targets had good binding ability with the main active components. Animal experiments showed that TDXD could effectively improve left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS), decrease left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs), reduce the area of myocardial fibrosis, and decrease serum BNP, LDH, CK-MB, IL-6, IL-1β, and TNF-α levels in HF rats. Meanwhile, TDXD could upregulate the expression of Bcl-2, downregulate the expression of Bax, and reduce cardiomyocyte apoptosis. At the same time, it was verified that TDXD could significantly decrease the expression of PI3K, P-Akt, and P-MAPK. Captopril showed similar effects.

Conclusions: Combining network pharmacological analysis and experimental validation, this study verified that TDXD could improve cardiac function and protect against cardiac injury by inhibiting the activation of PI3K/Akt and MAPK signaling pathways.