Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats

Xingjiang Xiong,Lian Duan,Yongmei Liu,Wei Liu,Xiaochen Yang,Yun Zhang,Xiaoke Li,Shengjie Li,Pengqian Wang

doi:10.1038/srep42965

Abstract

Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension.

Highlights

Maintenance of hypertension, because they may eventually lead to decompensation and ventricular extension, increasing the risk of heart failure and sudden death
A prospective case series involving 108 hypertensive patients with kidney yin deficiency syndrome revealed a significant reduction of 13.1 mmHg of systolic blood pressure (SBP) and 9.30 mmHg of diastolic blood pressure (DBP) by BSJYD25
The significant BP-lowering effect of Bu-Shen-Jiang-Ya decoction (BSJYD) has been confirmed in spontaneously hypertensive rats (SHRs); the possible cardioprotective mechanisms of BSJYD on hypertension may be related to up-regulating adiponectin and improving insulin resistance[27]

Summary

Introduction

Maintenance of hypertension, because they may eventually lead to decompensation and ventricular extension, increasing the risk of heart failure and sudden death. The mitogen-activated protein kinases (MAPKs) have been implicated as focal mediators of cardiac hypertrophy in both cell culture and genetically modified mouse models[15]. The extracellular signal-regulated kinase (ERK) signaling pathway, a branch of the greater MAPK signaling cascade, appears to induce a unique form of concentric cardiac hypertrophy[16]. There was little information available in literature about whether Chinese herbal medicine with anti-hypertensive effect could affect ERK pathway in LVH. Herbal compounds Bu-Shen-Jiang-Ya decoction (BSJYD) has been widely used in treating hypertension with kidney yin deficiency syndrome for many years. A prospective case series involving 108 hypertensive patients with kidney yin deficiency syndrome revealed a significant reduction of 13.1 mmHg of systolic blood pressure (SBP) and 9.30 mmHg of diastolic blood pressure (DBP) by BSJYD25. We aimed to examine how ERK signal transduction induces LVH and whether BSJYD inhibits LVH bioactivities through the ERK signaling pathway effectively

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