BAOXIN Granules Protected Mouse Model With Elevated Afterload From Cardiac Hypertrophy by Suppressing Both Inflammatory Reaction and Collagen Deposition.

Xu Qiu,Dong Zhang,Yuhui Wang,Zhao Dong,Guining Jiang,Defeng Li,Ji Ma,Haozhe Shi,Xiao Lin,Yujing Shi,George Liu

doi:10.3389/fphys.2019.00820

Abstract

BAOXIN Pill was reported to be effective clinically for chronic heart failure based on the principles of traditional Chinese medicine (TCM), invigorating qi and activating blood. The present study evaluated preclinically the effects of the improved dosage form, BAOXIN Granules, on cardiac hypertrophy. Transverse aortic constriction (TAC) was performed in mice to model cardiac hypertrophy by aortic stenosis for 4 weeks. The sham and TAC group were intragastrically administrated with saline as the controls. Two treatment groups were administrated orally with 10 mg/kg⋅d Enalapril (positive control) or 0.77 g/kg⋅d BAOXIN Granules for 4 weeks respectively. The effects were evaluated by echocardiography, morphology, and biological markers for cardiac function. The specific genes involved in inflammation and fibrosis were also examined for their expressions to investigate the pathways involved in early heart failure. Just as Enalapril, BAOXIN Granules administration markedly attenuated left ventricular hypertrophy and improved heart function as evidenced by echo cardiography, morphology. Accordingly, the biomarkers of the early stage heart failure, ANP, BNP and β-MHC, were decreased in the two treatment groups. We also found that mRNA expressions of some inflammatory factors and fibrosis associated genes were down-regulated in the tissue of heart after treatment. BAOXIN Granules may protect the heart from myocardial hypertrophy caused by increasing left ventricular afterload. It can suppress both inflammatory reaction and collagen deposition during pressure overload. BAOXIN Granules is advised to be tested in clinical trials for heart failure in the future.

Highlights

Cardiac hypertrophy has been demonstrated to be an independent risk factor for morbidity and mortality of cardiovascular diseases (Levy et al, 1990; Reichek et al, 2009; Zile et al, 2014)
After 4 weeks of BAOXIN Granules treatment, no significant difference in body weight (BW) was observed in four groups and the heart weight (HW) to BW ratio increased significantly in Control group compared to Sham Group (Supplementary Figure 2)
Compared with the control group, left ventricular (LV) systolic function, as reflected by EF% (Figure 2A), FS% (Figure 2B), LV Mass (Figure 2C), and LV end-systolic volume (Figure 2D) was significantly increased in the BAOXIN Granules treated mice as well as Enalapril after Transverse aortic constriction (TAC) surgery. Both BAOXIN Granules and Enalapril significantly attenuated the decline of cardiac function induced by TAC surgery

Summary

Introduction

Cardiac hypertrophy has been demonstrated to be an independent risk factor for morbidity and mortality of cardiovascular diseases (Levy et al, 1990; Reichek et al, 2009; Zile et al, 2014). Myocardial hypertrophy, with main feature of left ventricular mass and cardiomyocytes volume increases, is a compensatory reaction against various physiological and pathological process, such as BAOXIN Granules Protected Cardiac Hypertrophy hypertension, ischemic heart disease, and genetic cardiac defects (Komuro, 2001). Preventing the progress and even reversing the already presented cardiac hypertrophy is of great importance. In this status, heart undergoes a series of pathological processes such as energy metabolism, remodeling, and inflammation detailed mechanisms remain to be further investigated (Allard et al, 1994; Reichek et al, 2009). There is still lack of effective anti-hypertrophy intervention with little side effect

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Discussion

Conclusion