Current Issue : July - September Volume : 2016 Issue Number : 3 Articles : 6 Articles
Incretins are known to have cardioprotective effects. Drugs that augment the incretin levels particularly GLP-1 are DPP-4 Inhibitors. These new class of drugs are the most promising in Type 2 diabetes. Saxagliptin, a DPP-4 inhibitor is of particular importance because of its weight neutral, reduction in HbA1c, safety profile and patient tolerance. It is widely used as monotherapy or in combination with other oral anti-diabetics. Diabetes is known as high risk factor for cardiovascular consequences such as ischemia. Reperfusion is inevitable to prevent further damage leading to ischemic reperfusion injury. I/R injury aggravate generation of reactive oxygen species leading to inflammation. Inflammation is the cornerstone of tissue injury and repair. RISK pathway and NF-κB mediated cytokines such as, TNF-α, IL-6, IL-10 play an important role in inflammatory process. Diabetic heart was further prone to undergo extensive damage caused by inflammation. The aim of the present study was to investigate the anti-inflammatory role of saxagliptin in type 2 diabetic rats in streptozocin induced myocardial infarction. Normal and diabetic rats were randomized to receive saxagliptin 5 mg/kg b.wt. orally for a period of 4 weeks and were subjected to 30-min left anterior descending artery coronary artery occlusion followed by 4 hrs of reperfusion. Percentage left ventricle infarction and inflammatory markers such as MPO, TNF- α, IL-6, IL-10 were analysed in the study. Saxagliptin at the dose of 5 mg/kg decreased the levels of MPO, TNF-α and IL-6 in treated groups. Anti-inflammatory marker IL-10 significantly increased when treated with saxagliptin. Saxagliptin decreased the infarct size and showed significant cardioprotective action by anti-inflammatory mechanisms....
Agomelatine is a 5HT2C receptor antagonist. Hyperfunction of brain 5HT2C receptor is suggested to be involved in anxiety. The effect of agomelatine was explored in some acute and chronic behavioural models of anxiety. The models used for studying acute anxiety were elevated plus maze (EPM), hole board test (HBT), open field test (OFT), light/dark exploration (LDA) and marble burying test (MBT). Agomelatine (1, 10 and 30 mg/kg, i.p) and meta-chlorophenyl piperazin (m-CPP) (1\nmg/kg, i.p) were used for acute study. The effects of chronic administration of agomelatine (1, 10 and 30 mg/kg, p.o for 15 days) were investigated on two different anxiety models, the elevated T-maze and open field test. Cumulative Concentration Response Curve (CCRC) of 5HT2 was plotted using mice fundus at the end of treatment schedule. In acute study, agomelatine significantly (p<0.05) increased the time spent, number of entries in open arms, number of head dips and rearings, number of squares travelled, the time spent in light box, no. of transitions and number of marbles buried as compared to control in EPM, HBT, OFT, LDA and MBT respectively. Agomelatine significantly reversed the effects of m-CPP (1 mg/kg, i.p). In chronic study, agomelatine significantly (p<0.05) impaired inhibitory avoidance and facilitated escape latency and did not impair locomotion in open field test. CCRC of 5-HT2 was shifted towards the right with suppression of maxima in mice treated with agomelatine. The present investigation demonstrates that agomelatine has value in the treatment of acute anxiety states as well as in generalised anxiety disorders and panic disorders....
Aim of the present study was to analyze whether rutin has the potential to inhibit or attenuate ethanol withdrawal induced handling convulsion in mice or not. Male mice received an ethanol containing (1.6%, 3.6%, 6.3%) liquid diet for 10 days and were tested for withdrawal signs and symptoms at 2, 4, 6, 8, 10 h after termination of the diet on day 11. The anticonvulsant activity of rutin (50, 75 and 100 mg/kg, i.p.) was evaluated in mice models of pentylenetetrazole. In the PTZ-induced seizure model, rutin treatment was given where acute treatment at low dose showed protection against convulsion while treatment at high dose of rutin showed complete absence of convulsions....
Oxidative stress is one of the major pathological mechanisms involved in cerebral ischemia and reperfusion injury. Diabetes is one of the major risk factor for cerebral ischemic stroke. Increased base line levels of oxidative stress in diabetes will lead to cerebral ischemic damage. In pathological conditions such as cerebral ischemia/reperfusion injury free radical production is more than their elimination through antioxidant defence mechanisms leading to increased injury of brain. Newer anti-diabetic drugs of the class DPP-4 inhibitors such as, vildagliptin and alogliptin was reported to have antioxidant properties apart from its antihyperglycemic activity. Therefore the aim of the present study was to evaluate the antioxidant effect of vildagliptin and alogliptin against cerebral infarction induced ischemia reperfusion injury in normal and STZ induced diabetic wistar rats. Cerebral infarction was induced by bilateral common carotid artery occlusion followed by 4 hr reperfusion. Percent infarction, oxidative stress markers such as malondialdehyde, superoxide dismutase and catalase and biochemical parameters such as glucose, LDH, SGOT and CK-BB were measured. Treatment with vildagliptin and alogliptin for a period of four weeks produced significant reduction in percent cerebral infarct volume. At vildagliptin dose 10 mg/kg dose there was a significant reduction in oxidative stress markers like MDA, LDH, SGOT and CK-BB in diabetic group when compared to normal group and in contrast significant increase in antioxidant markers like superoxide dismutase and catalase levels. Similar to vildagliptin, alogliptin at the dose of 30 mg/kg also showed significant reduction in oxidative stress markers like MDA, LDH, SGOT and CK-BB in diabetic group when compared to normal group and in contrast significant increase in antioxidant markers like superoxide dismutase and catalase levels. Vildagliptin and alogliptin showed significant cerebroprotective effect by antioxidant mechanisms....
Leptin is synthesized and secreted by white adipose tissue, by acting on hypothalamic nuclei it decreases appetite and\nincreases energy expenditure through sympathetic activation to decreases adipose tissue mass. Leptin also activate sympathetic\nnervous system in kidney, spleen, heart and hind limb. Leptin secretion decreases during fasting and increased after several\ndays of overfeeding to regulate energy balance. Leptin act on Ob-Rb receptor which is tyrosine kinase receptor and activate\nJAK/STAT pathway, PI3 kinase signaling pathway and Mitogen Activated Protein (MAP) kinas signaling. Leptin induced anorexic\neffect is mediated by synthesis of melanocyteââ?¬â??stimulating hormone in POMC neuron which act on MCR-3 and MCL-4 leptin\ninduced sympathetic activation is also mediated by STAT3 activation in propiriomeclanortin neuron. Released melanocyte\nstimulating hormone act on MCR-4 receptor. Most of obese human have high circulating leptin but remaining obese indicates\nresistance to anorexic and weight lowering effect of leptin. Leptin induce anorexic effect and sympathetic nervous system\nstimulatory effect is mediated by different area of brain. Thus leptin resistance is selective in obesity i.e. increased leptin level\nshows resistance to anorexic and weight lowering effect of leptin with preservation of sympatho activation. Although leptin\nstimulate renal SNS, acute administration of leptin does not significantly affect blood pressure because of release of NO and\nnatriuresis. But chronic hyperleptemia in obesity induces increased renal sympathetic activity and rise in BP by activation of\nNa+K+ATPase pump and inhibition of inhibitory effect of NO on Na+K+ATPase pump, which increases Na+ and water reabsorption\nand rise arterial blood pressure....
Biogenic amines are a collection of endogenous molecules that play pivotal roles as\nneurotransmitters and hormones. In addition to the ââ?¬Å?classicalââ?¬Â biogenic amines resulting\nfrom decarboxylation of aromatic acids, including dopamine (DA), norepinephrine,\nepinephrine, serotonin (5-HT), and histamine, other biogenic amines, present at much\nlower concentrations in the central nervous system (CNS), and hence referred to\nas ââ?¬Å?traceââ?¬Â amines (TAs), are now recognized to play significant neurophysiological\nand behavioral functions. At the turn of the century, the discovery of the trace\namine-associated receptor 1 (TAAR1), a phylogenetically conserved G protein-coupled\nreceptor that is responsive to both TAs, such as Ã?²-phenylethylamine, octopamine,\nand tyramine, and structurally-related amphetamines, unveiled mechanisms of action\nfor TAs other than interference with aminergic pathways, laying the foundations for\ndeciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1.\nAlthough, its molecular interactions and downstream targets have not been fully\nelucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates\nPKA and PKC signaling and interferes with the Ã?²-arrestin2-dependent pathway via\nG protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct\ncontrol over DA and 5-HT neuronal firing and release, which has profound implications\nfor understanding the pathophysiology of, and therefore designing more efficacious\ntherapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic\ndysregulation, including Parkinsonââ?¬â?¢s disease, schizophrenia, mood disorders, and\naddiction. Indeed, the recent development of novel pharmacological tools targeting\nTAAR1 has uncovered the remarkable potential of TAAR1-based medications as\nnew generation pharmacotherapies in neuropsychiatry. This review summarizes recent\ndevelopments in the study of TAs and TAAR1, their intricate neurochemistry and\npharmacology, and their relevance for neurodegenerative and neuropsychiatric disease....
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