Use of ginseng to reduce post-myocardial adverse myocardial remodeling: applying scientific principles to the use of herbal therapies

Abstract

Cardiac remodeling involves molecular, cellular, and interstitial changes that manifest clinically as changes in size, shape, and function of the heart after injury or stress stimulation and was initially coined to describe the prominent changes that occur after myocardial infarction (MI) [1]. Adverse ventricular remodeling during the healing phase after acute MI continues to be an important problem that impacts adult cardiology practice. Indeed, coronary artery disease is now the most common cause of heart failure in westernized countries and is rising in prevalence in India and China. Most clinicians and cardiovascular researchers recognize that significant left ventricular (LV) remodeling occurs during infarct healing, and optimal healing is critical for survival with a favorable outcome. Over the last three decades, several laboratories have been actively searching for specific molecular targets that may lead to the development of therapies and strategies to optimize postinfarct healing, prevent adverse remodeling, and improve clinical outcome. However, specific therapy to optimize healing and prevent adverse post-MI remodeling is currently lacking and only suboptimal medical therapy currently exists. Hearts continue to enlarge after MI, and heart failure is a growing burden. At present, ginseng is one of the most extensively used alternative medications throughout the world and has appeared in the pharmacopoeias of several western countries, including the United States and European countries with indications for cardiovascular diseases and other conditions [2]. In this issue, Yin H et al. showed that the active ingredient of the ginseng extract, ginsenoside-Rg1, enhances angiogenesis and reduces adverse ventricular remodeling in a rat model of MI [3]. Ginsenoside-Rg1 is the most prevalent and active constituent of ginseng. Three major targets of adverse myocardial remodeling were the key mediators of the cardioprotective effects seen with ginsenoside-Rg1administration: stimulation of the PI3K/ Akt [and inhibition of p38 mitogen-activated protein kinase (MAPK)] pathway with improvement in post-MI angiogenesis and reduction in myocardial fibrosis (Fig. 1). These beneficial effects resulted in reduced LV dilation and a modest improvement in systolic function based on the assessment of fractional shortening and ejection fraction. PI3K inhibition using LY294002 also reduced the phosphorylation of the p38 MAPK pathway which is known to play a key role in inducing inflammatory cytokines and apoptotic cell death. The PI3K/Akt pathways mediate cardioprotective effects in a wide variety of pathological conditions including important anti-apoptotic effects and modulation of cellular growth and metabolism [4]. However, pharmacological inhibition of PI3K signaling using LY294002 cannot distinguish isoform-specific effects of PI3K signaling which is well established to play a differential role in myocardial ischemic injury [4]. In addition, LY294002 is a potent blocker of voltage-gated K channels in cardiomyocytes [5]. Thus, off-target effects Clinical implications: Yin H et al. Ginsenoside-Rg1 enhances angiogenesis and ameliorates ventricular remodeling in a rat model of myocardial infarction. S. Bodiga :G. Y. Oudit (*) Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta T6G 2S2, Canada e-mail: gavin.oudit@ualberta.ca