Deciphering mechanism of the herbal formula WuShen in the treatment of postinfarction heart failure

Huiliang Qiu; Zihan Huang; Haiming Cao; Zezhao Zhang; Jin Ma; Xiaoqing Li; Shen Huang; Xiong Li; Wencong Qiu; Zicong Zhao; Chunlan Ji; Lihua Huang; Wei Jiang; Zhong-Qi Yang; Shaoxiang Xian; Huanlin Wu; Weihui Lu; Chunhua Ding

doi:10.1016/j.phymed.2021.153878

Graphical abstract published by Phytomedicine — Graphical abstract · Published by Phytomedicine · CC BY-NC-ND 4.0

Why the study?

Clinical studies have reported the effectiveness of the herbal formula WuShen in treating cardiovascular diseases, but relevant basic research was rarely conducted.

Does herbal formula WuShen improve cardiac function and reduce arrhythmias in a rat model of post-myocardial infarction heart failure?

Structured PICO

Does herbal formula WuShen improve cardiac function and reduce arrhythmias in a rat model of post-myocardial infarction heart failure?

P

Population

Rat model of post-myocardial infarction (MI) heart failure (HF)

I

Intervention

Herbal formula WuShen (WS)

O

Outcome

Cardiac function, adverse cardiac remodeling, and experimental arrhythmiassurrogate

Implication

The herbal formula WuShen improves cardiac function and reduces arrhythmia susceptibility in a rat model of post-infarction heart failure by inhibiting adverse cardiac remodeling pathways.

Abstract

BACKGROUND: Numerous clinical studies reported the effectiveness of herbal formula WuShen (WS) in treating cardiovascular diseases, yet relevant basic research was rarely conducted. METHODS AND RESULTS: Twelve main bioactive compounds of WS decoction were identified using the ultra-performance liquid chromatography-LTQ-Orbitrap mass spectrometer. A total of 137 active compounds with 613 targets were predicted by network pharmacology; their bioinformatic annotation and human microarray data suggested that wounding healing, inflammatory response, and gap junction were potentially the major therapeutic modules. A rat model of post-myocardial infarction (MI) heart failure (HF) was used to study the effects of WS on cardiac function, adverse cardiac remodeling, and experimental arrhythmias. Rats treated with WS led to a significantly improved pump function and reduced susceptibility to both ventricular tachycardia and atrial fibrillation, and restricted adverse cardiac remodeling partly via inhibiting TGFβ1/SMADs mediated extracellular matrix deposition and Rac1/NOX2/CTGF/Connexin43 -involved gap junction remodeling. CONCLUSIONS: The present study highlights that WS can be applied to the treatment of heart failure and the upstream therapy for atrial fibrillation and ventricular tachycardia through its preventive effect on adverse cardiac remodeling.