Qishen Granule (QSG) Inhibits Monocytes Released From the Spleen and Protect Myocardial Function via the TLR4-MyD88-NF-κB p65 Pathway in Heart Failure Mice.

Yanqin Li,Xiangning Liu,Chun Li,Lingwen Cui,Wei Wang,Yizhou Liu,Xiaoqian Sun,Gang Wang,Tianhua Liu,Xu Chen,Xuan Li,Yong Wang

doi:10.3389/fphar.2022.850187

Yanqin Li, Xiangning Liu + Show 10 more

Open Access

https://doi.org/10.3389/fphar.2022.850187

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Abstract

Preliminary clinical and basic researches have proved that Qishen granule (QSG) is an effective prescription for treating heart failure (HF) in China, with a characteristic of regulating the ratio of M1/M2 macrophage in the myocardium. However, the regulative mechanism of monocytes targeting the cardio-splenic axis has not been fully elucidated. This study aimed to investigate the effects and mechanism of QSG inhibiting the release of splenic monocytes and the recruitment of myocardial tissue both in vivo and in vitro. Experiments in mice with acute myocardial infarction (AMI)-induced HF demonstrated that QSG could exert anti-inflammatory effects by inhibiting splenic monocytes release and phenotypic changes. Moreover, in vitro experiments indicated QSG could inhibit LPS-stimulated macrophage-conditioned medium (CM)-induced H9C2 cardiomyocyte injury by upregulating the key proteins in TLR4-MyD88-NF-κB p65 pathway. In addition, knockdown or overexpression of TLR4 in H9C2 cells further confirmed that QSG could attenuate inflammatory injury in cardiomyocytes via the TLR4-MyD88-NF-κB p65 pathway. Overall, these data suggested that QSG could improve cardiac function and reduce the inflammatory response in AMI-induced HF by inhibiting splenic monocytes release, and protecting myocardial function via the TLR4-MyD88-NF-κB pathway in heart failure mice.

Highlights

Myocardial infarction is one of the most common and important causes of heart failure (HF)
Echocardiography, HE staining, creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) detection were performed to determine whether Qishen granule (QSG) has a protective effect on cardiac function
Evidence suggested that QSG could inhibit the release of CK-MB and LDH into serum compared to the model group (Figure 1E) (p < 0.001)

Summary

Introduction

Myocardial infarction is one of the most common and important causes of heart failure (HF). QSG, Heart Failure, Splenic Monocytes, TLR4-MyD88-NF-κB p65, Inflammation. The latest basic and clinical studies have shown that the inflammation induced by crosstalk between the heart and the spleen (the so-called cardio-splenic axis) dominates the inflammatory injury during the HF process (Jahng et al, 2016; Dunford et al, 2017; Saito et al, 2020). The activation of monocytes in the spleen is the critical resource of myocardial inflammation in HF (Ismahil et al, 2014). In the acute phase of myocardial injury, the spleen mobilizes its Ly6Chigh-led monocytes and releases them into the injury zone (Nahrendorf et al, 2010; Tian et al, 2016), and subsequently activated M1 macrophages to exert pro-inflammatory and phagocytic functions. Inhibiting inflammation and polarization of macrophages to M1 may be a promising treatment option for HF (Wallert et al, 2019; Heimerl et al, 2020)

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