Pema Raj

Potential of resveratrol in the treatment of heart failure

The concept of food has expanded beyond its traditional role of survival and hunger satisfaction, to include a role in the prevention and treatment of disease. Polyphenols are classes of compounds that are synthesized by plants to serve a wide variety of functions including growth pollination and defense. These compounds have recently received increased attention in medical research. In this group, one of the most studied has been resveratrol (3,5,4,-trihydroxystilbene), a polyphenol, which is found predominantly in grapes and berries. Over the past two decades, researchers have studied the ability of resveratrol to prevent or reverse the development of abnormalities in heart structure and function in animal models of heart disease and heart failure. The results from animal studies have been promising, and very recently, this knowledge has been translated into examining the efficacy of resveratrol in humans with heart disease/failure. In this review we will discuss the current status of resveratrol research on cardioprotection.

A novel hemp seed meal protein hydrolysate reduces oxidative stress factors in spontaneously hypertensive rats.

This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH) in spontaneously hypertensive rats (SHR). Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old) SHRs were divided into three groups (8 rats/group) and fed diets that contained 0.0%, 0.5% or 1.0% (w/w) HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC) and superoxide dismutase (SOD), catalase (CAT) and total peroxides (TPx) levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05) increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.

An overview of the efficacy of resveratrol in the management of ischemic heart disease

Ischemic heart disease is a leading cause of cardiac dysfunction and subsequent morbidity and mortality around the world. New therapies are required to complement or enhance the existing treatment regimen for the management of ischemic heart disease–related clinical complications. In this regard, compounds derived from natural sources have recently gained attention for their cardioprotective properties. In particular, the potential of food‐derived compounds that exhibit medicinal properties (termed nutraceuticals) appears promising, an example being the plant polyphenol resveratrol. In the past two decades, many preclinical and a few pilot clinical studies have shown that resveratrol is beneficial in protecting against cardiovascular disease. In this short review, we will discuss current evidence on the efficacy of resveratrol in preventing or reversing deleterious effects on the heart in the setting of ischemic heart disease.

Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors improve prognosis in patients with post-myocardial infarction (MI) related cardiac dysfunction. Resveratrol is a polyphenol that has been reported to be beneficial in hypertension, ischemic heart disease, and cardiotoxicity in preclinical studies. Accordingly, we investigated the comparative and combinatorial efficacy of resveratrol and perindopril (ACE inhibitor) treatment on MI-related cardiac remodeling and contractile dysfunction. METHODS Left anterior descending artery-ligated and sham-operated male Sprague-Dawley rats were gavaged with vehicle, resveratrol, perindopril, and combination of resveratrol+perindopril (2.5 mg/kg bodyweight/day) for 8 weeks (starting immediately after acute MI). Echocardiography was performed to assess cardiac structure and function at baseline and 8 weeks. RESULTS At 8 weeks, vehicle-MI rats had a significantly lower left ventricular ejection fraction (LVEF) and increased LV dilatation compared to vehicle-sham rats. MI rats treated with resveratrol, perindopril and a combination of both had significantly improved LVEF and reduced LV dilatation. Vehicle-treated MI rats also had increased level of lipid peroxidation product- malondialdehyde (MDA), proinflammatory protein- tumor necrosis factor-alpha (TNF-α) and cardiac fibrosis marker- collagen and decreased enzymatic activity of superoxide dismutase and catalase compared to vehicle-sham rats. Resveratrol, perindopril and combination of both significantly prevented the /ed to determine systolic functional parameter increase in MDA, TNF-α and collagen and improved the activity of superoxide dismutase and catalase in MI rats compared to vehicle-MI rats. CONCLUSION Treatment with resveratrol or perindopril was equivalent in significantly improving remodeling and attenuation of contractile dysfunction in MI rats. Combination treatment also attenuated the cardiac abnormalities. The improvement in cardiac abnormalities may partly be through reducing oxidative stress by preventing the decrease in the activity of superoxide dismutase and catalase, and decreasing cardiac inflammation and fibrosis.

Disparate Effects of Stilbenoid Polyphenols on Hypertrophic Cardiomyocytes In Vitro vs. in the Spontaneously Hypertensive Heart Failure Rat

Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,4′-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,2′,6′-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown, abolished these anti-hypertrophic effects. In contrast, resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxation time (an indicator of diastolic dysfunction), and this was improved by stilbenoid treatment. In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy, a major risk factor for heart failure, may be context-dependent and requires further study.

Conjugated linoleic acid prevents high glucose-induced hypertrophy and contractile dysfunction in adult rat cardiomyocytes.

Diabetes mellitus is associated with increased risk and incidence of cardiovascular morbidity and mortality, independently of other risk factors typically associated with diabetes such as coronary artery disease and hypertension. This promotes the development of a distinct condition of the heart muscle known as diabetic cardiomyopathy. We have previously shown that conjugated linoleic acid (CLA) prevents endothelin-1-induced cardiomyocyte hypertrophy. However, the effects of CLA in preventing alterations in cardiomyocyte structure and function due to high glucose are unknown. We therefore hypothesized that CLA will have protective effects in an in vitro model of diabetic cardiomyopathy using adult rat cardiomyocytes exposed to high glucose. Our results demonstrate that subjecting adult rat cardiomyocytes to high glucose (25 mmol/L) for 24 hours significantly impaired the contractile function as evidenced by decreases in maximal velocity of shortening, peak shortening, and maximal velocity of relengthening. High glucose-induced contractile dysfunction was inhibited by pretreatment with CLA (30 μmol/L; 1 hour). In addition to contractile aberrations, exposing adult rat cardiomyocytes to high glucose for 48 hours induced cardiomyocyte hypertrophy. High glucose-induced cardiomyocyte hypertrophy was likewise prevented by CLA. The antihypertrophic effects of CLA were abolished when cardiomyocytes were pretreated with the pharmacologic inhibitor of peroxisome proliferator-activated receptor γ, GW9662 (1 μmol/L). In conclusion, our findings show that exposing cardiomyocytes to high glucose results in cardiomyocyte functional and structural abnormalities, and these abnormalities are prevented by pretreatment with CLA and mediated, in part, by peroxisome proliferator-activated receptor γ activation.

Supplementation of Type 1 Diabetic Rats with Carrot Powder Lowers Blood Glucose without Improving Cardiac Structure and Function

Foods and food bioactives have shown to be effective in preventing some human disease conditions. In this study, we examined the effects of carrot powder, rich in carotenoids, as a dietary supplement for the prevention of cardiac anomalies in streptozotocin (STZ) induced type 1 diabetic rats. Male Wistar rats were fed either control or carrot powder containing diet for 3 weeks. Type 1 diabetes was induced with STZ injection (65 mg/kg body weight) in half of the rats in each group. All rats were continued on their respective diet for a further 9 weeks. Cardiac structural and functional parameters were measured using echocardiography at 8 weeks post STZ administration. In comparison to non-diabetic rats, diabetic rats showed significant increase in isovolumetric relaxation time and a significant decrease in systolic function parameter, cardiac output. Left ventricular internal dimension and left ventricular posterior wall thickness were significantly higher in diabetic animals. Blood glucose levels were significantly lower in carrot supplemented diabetic rats when compared with non-treated diabetic rats. Diabetic rats treated and untreated had elevated level of lipid peroxidation. Catalase levels were significantly elevated in the carrot powder supplemented diabetic rats when compared to the control rats. Carrot supplementation lowered blood glucose levels significantly but did not normalize it to control levels. It had no effect on cardiac abnormalities and anti-oxidant status in rats with type 1 diabetes.