Cardiac hypertrophy (CH) is an adaptive response of the heart to pressure overload. It is a common pathological feature in the natural course of some major cardiovascular diseases, like, hypertension and myocardial infarction. Cardiac hypertrophy is strongly associated with an increased risk of heart failure and sudden cardiac death. The complex and dynamic pathophysiological mechanisms of CH has been the focus of intense scientific investigation, in an effort to design preventive and curative strategies. Oxidative stress has been identified as one of the key contributing factors in the development of cardiac hypertrophy. In this review, evidences supporting the oxidative stress as a cause of cardiac hypertrophy with emphasis on mitochondrial oxidative stress and possible options for pharmacological interventions have been discussed. Reactive oxygen species (ROS) also activate a broad variety of hypertrophy signaling kinases and transcription factors, like, MAP kinase, NF K-B, etc. In addition to profound alteration of cellular function, ROS modulate the extracellular matrix function, evidenced by increased interstitial and perivascular fibrosis. Translocator protein (TSPO) present in the outer mitochondrial membrane is known to be involved in oxidative stress and cardiovascular pathology. Recently, its role in cardiac hypertrophy has been reported by us. All these evidences strongly provide support to beneficial role of drugs which selectively interfere with the generation of free radicals or augment endogenous antioxidants in cardiac hypertrophy.

Abstract: The stem bark of Terminalia arjuna (Roxb.) is used by the Ayurvedic physicians in India for the treatment of various cardiovascular diseases, collectively referred to as hritroga. It has been extensively studied in animal models to demonstrate cardioprotective properties, ranging from positive inotropic- , hypolipdemic-, coronary vasodilatory- and antioxidant effects to induction of stress protein in heart. Various bioactive compounds, like triterpinoids, tannins, flavonoids and minerals have been isolated from the stem bark. A number of clinical studies have also reported its beneficial effects in patients of chronic stable angina, endothelial dysfunction, heart failure and even ischemic mitral regurgitation. However, there are some identified lacunae, like standardisation of the ‘drug’, toxicity studies along with pharmacological interactions with other drugs and large multicentre randomized clinical trials, before its use by modern medicine is acceptable.

Genistein, an isoflavone and a rich constituent of soy, possesses important regulatory effects on nitric oxide (NO) synthesis and oxidative stress. Transient and low release of NO by endothelial nitric oxide synthase (eNOS) has been shown to be beneficial, while high and sustained release by inducible nitric oxide synthase (iNOS) may be detrimental in pathological cardiac hypertrophy. The present study was designed to evaluate whether genistein could prevent isoproterenol-induced cardiac hypertrophy in male Wistar rats (150–200 g, 10–12 weeks old) rats. Isoproterenol (5 mg·(kg body weight)^–1) was injected subcutaneously once daily for 14 days to induced cardiac hypertrophy. Genistein (0.1 and 0.2 mg·kg^–1, subcutaneous injection once daily) was administered along with isoproterenol. Heart tissue was studied for myocyte size and fibrosis. Myocardial thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), catalase levels, and 1-OH proline (collagen content) were also estimated. Genistein significantly prevented any isoproterenol-induced increase in heart weight to body weight ratio, left ventricular mass (echocardiographic), myocardial 1-OH proline, fibrosis, myocyte size and myocardial oxidative stress. These beneficial effects of genistein were blocked by a nonselective NOS inhibitor (L-NAME), but not by a selective iNOS inhibitor (aminoguanidine). Thus, the present study suggests that the salutary effects of genistein on isoproterenol-induced cardiac hypertrophy may be mediated through inhibition of iNOS and potentiation of eNOS activities.

Myocardial fibrosis and oxidative stress accompany a number of cardiac disorders such as hypertrophic cardiomyopathy, hypertensive heart disease and cardiac failure. Stem bark of Terminalia arjuna has been advocated for cardiac ailments. The present study evaluated the effects of T. arjuna bark extract on myocardial fibrosis and oxidative stress induced by chronic beta-adrenoceptor stimulation. Aqueous extract of T. arjuna bark was evaluated at 63, 125 and 250 mg/kg given orally for antifibrotic and antioxidant effects in rats given the selective beta-adrenoceptor agonist isoprenaline (5 mg/kg s.c.) for 28 days. Captopril (50 mg/kg per day, given orally), an inhibitor of angiotensin-converting enzyme used as a standard cardioprotective drug, was used as a positive control. Isoprenaline caused fibrosis, increased oxidative stress and cardiac hypertrophy (increased heart weight : body weight ratio and cardiomyocyte diameter). The T. arjuna bark extract and captopril significantly prevented the isoprenaline-induced increase in oxidative stress and decline in endogenous antioxidant level. Both also prevented fibrosis but not the increase in heart weight : body weight ratio. T. arjuna protects against myocardial changes induced by chronic beta-adrenoceptor stimulation.