Aim-Excessive oxidative stress has been implicated in the pathology and complications of diabetes, which leads to myocardial ischemia reperfusion injury. The present study was designed to examine whether resveratrol (trans-3,5,4′-trihydroxystilbene), a polyphenolic compound present in red wine has a direct cardioprotective effect on diabetic myocardium.Methods-Resveratrol (2.5mg/kg b.wt/day) and L-NAME (25mg/kg b.wt/day) were administered orally for 15 days to streptozotocin (65mg/kg) induced diabetic rats. Sprague Dawley rats were divided into 5 groups i) Control ii) Diabetic iii) Diabetic+resveratrol iv) Diabetic+Resveratrol+L-NAME (nitric oxide synthase inhibitor), v) Diabetic+L-NAME. In our present study resveratrol demonstrated significant reduction in glucose level in diabetic rats. After the treatment, the hearts were excised and subjected to 30 min of global ischemia followed by 2 hours of reperfusion.Results-Resveratrol treated diabetic rats demonstrated significant reduction in glucose levels as compared to the non treated diabetic animals, improved left ventricular function throughout reperfusion compared to the diabetic or L-NAME treated animals (dp/dt max 1457 ± 51 vs 999 ± 44 mmHg/sec at 120 min reperfusion). Cardioprotection from ischemic injury in resveratrol treated diabetic rats showed decreased infarct size (42% vs 51%) and cardiomyocyte apoptosis (35% vs 40%) by TUNEL assay. Resveratrol produced significant induction of p-AKT, p-eNOS, Trx-1, HO-1 and VEGF in addition with increased activation of Mn-SOD activity in diabetic animals compared to non-diabetic animals. However treatment with L-NAME in resveratrol treated and non-treated diabetic animals demonstrated significant downregulation of the above mentioned protein expression profile and MnSOD activity. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HO-1 and VEGF in addition with increased MnSOD activity and reduced blood glucose level. Thus this study shows a novel mechanism of pharmacological preconditioning with resveratrol in the diabetic myocardium. Conclusion-In NIH Public Access

Homeostasis of blood glucose by insulin involves stimulation of glucose uptake by translocation of glucose transporter Glut-4 from intracellular pool to the caveolar membrane system. In this study we examined resveratrol (RSV)-mediated Glut-4 translocation in the streptozotocin (STZ)-induced diabetic myocardium. The rats were randomized into three groups: Control (Con), Diabetes Mellitus (DM) (STZ 65 mg/kg b.w., i.p.) & DM + RSV (2.5 mg/kg b.wt. for 2 weeks orally) (RSV). Isolated rat hearts were used as per the experimental model. RSV induced glucose uptake was observed in vitro with H9c2 cardiac myoblast cells. Decreased blood glucose level was observed after 30 days (375 mg/dl) in RSV-treated rats when compared to DM (587 mg/dl). Treatment with RSV demonstrated increased Adenosine Mono Phosphate Kinase (AMPK) phosphorylation compared to DM. Lipid raft fractions demonstrated decreased expression of Glut-4, Cav-3 (0.4, 0.6-fold) in DM which was increased to 0.75-and 1.1-fold on RSV treatment as compared to control. Increased Cav-1 expression (1.4-fold) in DM was reduced to 0.7-fold on RSV treatment. Increased phosphorylation of endothelial Nitric Oxide Synthase (eNOS) & Akt was also observed in RSV compared to DM (P< 0.05). Confocal microscopy and co-immunoprecipitation studies demonstrated decreased association of Glut-4/Cav-3 and increased association of Cav-1/eNOS in DM as compared to control and converse results were obtained on RSV treatment. Our results suggests that the effect of RSV is non-insulin dependent and triggers some of the similar intracellular insulin signalling components in myocardium such as eNOS, Akt through AMPK pathway and also by regulating the caveolin-1 and caveolin-3 status that might play an essential role in Glut-4 translocation and glucose uptake in STZ- induced type-1 diabetic myocardium.

Hypercholesterolemia (HC) is a common health problem that significantly increases risk of cardiovascular disease. Both statin (S) and resveratrol (R) demonstrated cardioprotection through nitric oxide dependent mechanism. Therefore the present study was undertaken to determine whether combination therapy with statin and resveratrol are more cardioprotective than individual treatment groups in ischemic rat heart model. The rats were fed rats with 2% high cholesterol diet and after 8 weeks of high cholesterol diet the animals were treated with statin (1mg/kg bw/day) and resveratrol (20mg/kg bw/day) for 2 weeks. The rats were assigned to: 1) Control (C) 2) HC 3) HCR 4) HCS and 5) HCRS. The hearts, subjected to 30 min global ischemia followed by 120 min reperfusion were used as experimental model. The left ventricular functional recovery (+dp/dt) was found to be significantly better in the HCRS (1926±43), HCR (1556±65) and HCS (1635±40) compared to HC group (1127±16). The infarct size in the HCRS, HCS and HCR groups were 37±3.6, 43±3.3 and 44 ±4.2 respectively compared to 53±4.6 in HC. The lipid level was found to be decreased in all the treatment groups when compared to HC more significantly in HCS and HCRS groups when compared to HCR. Increased phosphorylation of Akt and eNOS was also observed in all the treatment groups resulting in decreased extent of cardiomyocyte apoptosis but the extent of reduction in apoptosis was more significant in HCRS group compared to all other groups. In-vivo rat myocardial infarction (MI) model subjected to one week of permanent left descending coronary artery (LAD) occlusion documented increased capillary density in HCR and HCRS treated group when compared to HCS treatment group. We also documented increased β-catenin translocation and increased VEGF mRNA expression in all treatment groups. Thus, we conclude that the acute as well as chronic protection afforded by combination treatment with statin and resveratrol may be due to pro-angiogenic, antihyperlipidemic and anti-apoptotic effects and long term effects may be caused by increased neovascularization of the MI zone leading to less ventricular remodeling.

Diabetes mellitus is found in almost all populations and is emerging as a growing problem in developing countries. A large number of studies are in progress to fi nd natural sources, which are effective in reducing the intensity of diabetes. Quercetin, a constituent present in fruits and vegetables, was studied in two different doses (50 and 80 mg/kg body weight) for 45 days to assess its effect on streptozotocin induced diabetes. The blood glucose level was elevated in diabetic rats. Circulatory lipid peroxidation, vitamin C, vitamin E and enzymic antioxidants such as superoxide dismutase and catalase were analyzed. Alterations in the antioxidant defense were observed in diabetic animals compared to normal. Oral administration of quercetin to diabetic rats resulted in a decrease in the levels of blood glucose, plasma thiobarbituric acid reactive substances and hydroperoxides. Quercetin also resulted in the activities of superoxide dismutase, catalase coming to near normal, along with the levels of vitamin C and vitamin E. Quercetin at lower doses was found to be more effective. These result indicate that quercetin ameliorated the diabetes-induced changes in oxidative stress.

Background Insects are a living resource used for human nutrition, medicine, and industry. Several potential sources of proteins, peptides, and biopolymers, such as silk, chitin, and chitosan are utilized in industry and for biotechnology applications. Chitosan is an amino-polysaccharide derivative of chitin that consists of linear amino polysaccharides with d -glucosamine and N-acetyl- d -glucosamine units. Currently, the chief commercial sources of chitin and chitosan are crustacean shells that accumulate as a major waste product from the marine food industry. Existing chitin resources have some natural challenges, including insufficient supplies, seasonal availability, and environmental pollution. As an alternative, insects could be utilized as unconventional but feasible sources of chitin and chitosan. Scope and approach This review focuses on the recent sources of insect chitin and chitosan, particularly from the Lepidoptera, Coleoptera, Orthoptera, Hymenoptera, Diptera, Hemiptera, Dictyoptera, and Odonata orders. In addition, the extraction methods and physicochemical characteristics are discussed. Insect chitin and chitosan have numerous biological activities and could be used for food, biomedical, and industrial applications. Key findings and conclusions Recently, the invasive and harmful effects of insect species causing severe damage in agricultural crops has led to great economic losses globally. These dangerous species serve as potential sources of chitin and are underutilized worldwide. The conclusion of the present study provides better insight into the conversion of insect waste-derived chitin into value-added products as an alternative chitin source to address food security related challenges.

Background-The present study evaluated the reversal of diabetes-mediated impairment of angiogenesis in a myocardial infarction model of type 1 diabetic rats by intramyocardial administration of an adenoviral vector encoding thioredoxin-1 (Ad.Trx1). Various studies have linked diabetes-mediated impairment of angiogenesis to dysfunctional antioxidant systems in which thioredoxin-1 plays a central role. Methods and Results-Ad.Trx1 was administered intramyocardially in nondiabetic and diabetic rats immediately after myocardial infarction. Ad.LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. Myocardial function was measured by echocardiography 30 days after the intervention. The Ad.Trx1-administered group exhibited reduced fibrosis, oxidative stress, and cardiomyocyte and endothelial cell apoptosis compared with the diabetic myocardial infarction group, along with increased capillary and arteriolar density. Western blot and immunohistochemical analysis demonstrated myocardial overexpression of thioredoxin-1, heme oxygenase-1, vascular endothelial growth factor, and p38 mitogenactivated protein kinase-␤, as well as decreased phosphorylated JNK and p38 mitogen-activated protein kinase-␣, in the Ad.Trx1-treated diabetic group. Conversely, we observed a significant reduction in the expression of vascular endothelial growth factor in nondiabetic and diabetic animals treated with tin protoporphyrin (SnPP, a heme oxygenase-1 enzyme inhibitor), even after Ad.Trx1 therapy. Echocardiographic analysis after 4 weeks of myocardial infarction revealed significant improvement in myocardial functional parameters such as ejection fraction, fractional shortening, and E/A ratio in the Ad.Trx1-administered group compared with the diabetic myocardial infarction group. Conclusions-This study demonstrates for the first time that impairment of angiogenesis and myocardial dysfunction can be regulated by Ad.Trx1 gene therapy in streptozotocin-induced diabetic rats subjected to infarction. (Circulation. 2010; 121:1244-1255.)

Sildenafil citrate (SC), a drug for erectile dysfunction, is now emerging as a cardiopulmonary drug. Our study aimed to determine a novel role of sildenafil on cardioprotection through stimulating angiogenesis during ischaemia (I) reperfusion (R) at both capillary and arteriolar levels and to examine the role of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in this mechanistic effect. Rats were divided into: control sham (CS), sildenafil sham (SS), control + IR (CIR) and sildenafil + IR (SIR). Rats were given 0.7 mg/kg, (i.v) of SC or saline 30 min. before occlusion of left anterior descending artery followed by reperfusion (R). Sildenafil treatment increased capillary and arteriolar density followed by increased blood flow (2-fold) compared to control. Treatment with sildenafil demonstrated increased VEGF and Ang-1 mRNA after early reperfusion. PCR data were validated by Western blot analysis. Significant reduction in infarct size, cardiomyocyte and endothelial apoptosis were observed in SC-treated rats. Increased phosphorylation of Akt, eNOS and expression of anti-apoptotic protein Bcl-2, and thioredoxin, hemeoxygenase-1 were observed in SC-treated rats. Echocardiography demonstrated increased fractional shortening and ejection fraction following 45 days of reperfusion in the treatment group. Stress testing with dobutamine infusion and echocardiogram revealed increased contractile reserve in the treatment group. Our study demonstrated for the first time a strong additional therapeutic potential of sildenafil by up-regulating VEGF and Ang-1 system, probably by stimulating a cascade of events leading to neovascularization and conferring myocardial protection in in vivo I/R rat model.

Oxidative stress plays a crucial role in disruption of neovascularization by alterations in thioredoxin-1 (Trx1) expression and its interaction with other proteins after myocardial infarction (MI). We previously showed that Trx1 has angiogenic properties, but the possible therapeutic significance of overexpressing Trx1 in chronic MI has not been elucidated. Therefore, we explored the angiogenic and cardioprotective potential of Trx1 in an in vivo MI model using transgenic mice overexpressing Trx1. Wild type (W) and Trx1 transgenic (Trx1 Tg/+ ) mice were randomized into W Sham (WS), Trx1 Tg/+ Sham (TS), WMI and TMI. MI was induced by permanent occlusion of LAD coronary artery. Hearts from mice overexpressing Trx1 exhibited reduced fibrosis and oxidative stress, and attenuated cardiomyocyte apoptosis along with increased vessel formation compared to WMI. We found significant inhibition of Trx1 regulating proteins, TXNIP and AKAP 12, and increased p-Akt, p-eNOS and p-GSK-3β, HIF-1α, β-catenin, VEGF, Bcl-2 and survivin expression in TMI compared to WMI. Echocardiography performed 30 days after MI revealed significant improvement in myocardial functions in TMI compared to WMI. Our study identifies a potential role for Trx1 overexpression and its association with its regulatory proteins TXNIP, AKAP12 and subsequent activation of Akt/GSK-3β/β-catenin/ HIF-1α-mediated VEGF and eNOS expression in inducing angiogenesis and reduced ventricular remodeling. Hence, Trx1 and other proteins identified in our study may prove to be potential therapeutic targets in the treatment of ischemic heart disease.