Garlic Oil Alleviates MAPKs‐ and IL‐6‐mediated Diabetes‐related Cardiac Hypertrophy in STZ‐induced DM Rats

Sheng-Huang Chang,Kun-Yu Teng,Wen-Yuan Lin,Sheng-Wei Chang,Chung-Jung Liu,Bor-Show Tzang,Chang-Hai Tsai,Wei-Wen Kuo,Hong Chen,Fuu-Jen Tsai,Chia-Hua Kuo,Chih-Yang Huang

doi:10.1093/ecam/neq075

Abstract

Garlic oil has been reported to protect the cardiovascular system; however, the effects and mechanisms behind the cardioprotection of garlic oil on diabetes-induced cardiaomyopathy are unclear. In this study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether garlic oil could protect the heart from diabetes-induced cardiomyopathy. Wistar STZ-induced diabetic rats received garlic oil (0, 10, 50 or 100 mg kg_1 body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction and cardiac pathologic hypertrophy responses were observed in diabetic rat hearts. Cardiac function was examined using echocardiography. In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Garlic oil treatment significantly inhibited the up-regulation in MAPK (e.g., p38, JNK and ERK1/2) and IL-6/MEK5/ERK5 signaling pathways in the diabetic rat hearts, reducing the levels of cardiac pathologic hypertrophy markers such as ANP and BNP, and improving the cardiac contractile function. Collectively, data from these studies demonstrate that garlic oil shows the potential cardioprotective effects for protecting heart from diabetic cardiomyopathy.

Highlights

Diabetes mellitus (DM) is one of the major risk factors for cardiovascular disease development, accounting for 80% of all diabetic mortality [1]
In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction
The results demonstrated that garlic oil treatment down-regulates activities of MAPKs (e.g., p38, JNK and ERK1/2) and IL6/MEK5/ERK5 signaling pathways, and reduces expressions of pathologic hypertrophy response genes such as ANP and BNP, which contributes to the improvement of cardiac contractile function

Summary

Introduction

Diabetes mellitus (DM) is one of the major risk factors for cardiovascular disease development, accounting for 80% of all diabetic mortality [1]. The mortality of cardiac disease in patients with diabetes is 2- to 4-fold higher than that in subjects without diabetes [2]. The destruction of cardiac function has been well documented in both clinical and experimental diabetes [3,4,5]. Several pathological processes may initiate myocyte injury and myocardial dysfunction in patients with diabetes. Diabetic cardiomyopathy, characterized by cardiac hypertrophy and the presence of diastolic and/or systolic contractile dysfunction, eventually leads to heart failure [6].

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