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Objectives: We investigated the effects of methanolic extract of Nyctanthes arbor-tristis (MNAT) 100, 200 and 400 mg/kg/day post-operative for 6 weeks on ECG, basal mean arterial blood pressure (MABP), heart rate, respiratory rate, vascular reactivity, antioxidant activities of enzyme superoxide dismutase (SOD) and catalase (CAT), levels of thiobarbituric acid reactive substances (TBARS), serum levels of leptin, adiponectin, glucose, triglycerides, cholesterol, uric acid, insulin, sodium and potassium in fructose-fed rats. Materials and Methods: A high-fructose-diet (fructose 10%, w/v) ad libitum for 6 weeks was used to induce hypertension in male Wistar rats (150–200 g). Sixty albino Wistar rats were randomly divided into a group of six, each group containing 10 animals. Group I was considered as normal control which received chow pellets and normal drinking water ad libitum for 6 weeks. Group II received fructose (10%) solution instead of normal drinking water for 6 weeks. Group III received fructose (10%) solution instead of drinking water ad libitum and MNAT at a dose of 100 mg/kg post-operative for 6 weeks. Group IV received fructose (10%) solution instead of drinking water ad libitum and MNAT at a dose of 200 mg/kg post-operative for 6 weeks. Group V received fructose (10%) solution instead of drinking water ad libitum and MNAT at a dose of 400 mg/kg post-operative for 6 weeks. Group VI received fructose (10%) solution instead of drinking water ad libitum and enalapril at a dose of 10 mg/kg post-operative for 6 weeks. Physiological parameters, ECG, heart rate, respiratory rate and blood pressure vascular reactivity to various drugs were measured and recorded by the invasive method. The antioxidant activities of enzyme SOD and CAT, levels of TBARS, along with serum levels of leptin, adiponectin, glucose, triglycerides, cholesterol, uric acid, insulin, sodium and potassium were measured. Cumulative concentrationresponse curve (CCRC) of Ang II and acetylcholine (Ach) was recorded. Results: MNAT treatment decreased MABP and altered vascular reactivity to various catecholamines. The activities of SOD and CAT enzymes exhibited a considerable increase and the levels of TBARS in the liver were reduced by MNAT treatment. MNAT has shown decrease in the plasma level of triglycerides, cholesterol, insulin and sodium while increase in plasma adiponectin and potassium levels. The CCRC of Ang II was shifted towards the right by MNAT treatment using an isolated strip of rat ascending colon. MNAT treatment increased the contractile characteristics of the rat ascending colon in the CCRC of ACh as compared to the fructose-treated group. MNAT treatment reduced fructose-induced tissue damage due to the consequence of metabolic syndrome (MetS). MNAT is rich in flavonoids and, therefore, has powerful antioxidant properties. The findings show that by battling oxidative stress caused by fructose (10%) and reducing Ang II activity, MNAT may be able to prevent the development of high blood pressure caused by fructose. Conclusion: MNAT has antihypertensive action and reverses MetS in the fructose-induced hypertensive rat model.
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Background & objectives: Insulin resistance associated with hyperinsulinaemia and overexpression of insulin receptors (IRs) have been intricately linked to the pathogenesis and treatment outcomes of the breast carcinoma. Studies have revealed that upregulated expression of IRs in breast cancer pathogenesis regulates several aspects of the malignant phenotype, including cell proliferation and metastasis. This study was aimed to investigate the pivotal role of an IR antagonist S961 on IR signalling and other biological parameters in MCF-7, MDA-MB-231 and T47D cell lines. Methods: The effect of human insulin and S961 on growth, proliferation rate and clonogenic potential of breast cancer cells was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay and clonogenic assay. The mRNA expression of IR isoforms (IR-A and IR-B) was measured in the breast carcinoma cells using quantitative PCR. Results: The study revealed that breast cancer cells predominantly expressed IR-A isoform and showed extensive growth and proliferation owing to IR overexpression. It was found that S961 downregulated the IRs (IR-A and IR-B) with nanomolar dose and efficiently blocked expression of IRs even in the presence of insulin. IR mRNA expression levels were significantly downregulated in the continued presence of S961. S961 also inhibited cellular proliferation and colony formation in breast tumour cells. Interpretation & conclusions: IR antagonist, S961 showed distinct antagonism in vitro and appeared to be a powerful therapeutic modality that might provide insight into the pathogenesis of impaired IR signalling.
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Background & objectives: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation & conclusions: High fructose feeding to rats and hamsters led to the development of insulin resistance, hyperglycaemia, endothelial dysfunction and oxidative stress. C. oil prevented development of thrombotic complications associated with insulin resistance perhaps by modulating genes involved in lipid and glucose metabolism. Further studies are required to confirm these findings.
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Background & objectives: WNIN/GR-Ob is a mutant obese rat strain with impaired glucose tolerance (IGT) developed at the National Institute of Nutrition (NIN), Hyderabad, India, from the existing 80 year old Wistar rat (WNIN) stock colony. The data presented here pertain to its obese nature along with IGT trait as evidenced by physical, physiological and biochemical parameters. The study also explains its existence, in three phenotypes: homozygous lean (+/+), heterozygous carrier (+/-) and homozygous obese (-/-). Methods: Thirty animals (15 males and 15 females) from each phenotype (+/+, +/-, -/-) and 24 lean and obese (6 males and 6 females) rats were taken for growth and food intake studies respectively. Twelve adult rats from each phenotype were taken for body composition measurement by total body electrical conductivity (TOBEC); 12 rats of both genders from each phenotype at different ages were taken for clinical chemistry parameters. Physiological indices of insulin resistance were calculated according to the homeostasis model assessment for insulin resistance (HOMA-IR) and also by studying U14C 2-deoxy glucose uptake (2DG). Results: WNINGR-Ob mutants had high growth, hyperphagia, polydipsia, polyurea, glycosuria, and significantly lower lean body mass, higher fat mass as compared with carrier and lean rats. These mutants, at 50 days of age displayed abnormal response to glucose load (IGT), hyperinsulinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperleptinaemia. Basal and insulin-stimulated glucose uptakes by diaphragm were significantly decreased in obese rats as compared with lean rats. Interpretation & conclusions: Obese rats of the designated WNIN/GR-Ob strain showed obesity with IGT, as adjudged by physical, physiological and biochemical indices. These indices varied among the three phenotypes, being lowest in lean, highest in obese and intermediate in carrier phenotypes thereby suggesting that obesity is inherited as autosomal incomplete dominant trait in this strain. This mutant obese rat model is easy to propagate, and can easily be transformed to frank diabetes model by dietary manipulation and thus can be used for screening anti-diabetic drugs.