Amelioration of Obesity, Glucose Intolerance, and Oxidative Stress in High-Fat Diet and Low-Dose Streptozotocin-Induced Diabetic Rats by Combination Consisting of “Curcumin with Piperine and Quercetin”

Curcumin is an important nutraceutical that has enormous potential for a variety of diseases, but the medicinal properties of curcumin cannot be utilized due to its low in vivo bioavailability. Therefore, in view of the foregoing, there is an extensive need for combinatorial extract “curcumin with piperine and quercetin” which may enhance bioavailability of oral curcumin by inhibiting the enzymes responsible for the metabolism of curcumin. Thus, the present study investigated the effect of combinatorial extract of curcumin on obesity, glucose intolerance, and oxidative stress in high fat diet and low-dose streptozotocin-induced rats. Oral administration of combinatorial extract for 28 days significantly (P < 0.05) reduced PGL (64.84%), PTG (88.94%), LDL (26.38%) and PTC (50.23%) levels, respectively and improved glucose tolerance (P < 0.05) significantly to exogenously administered glucose (2 g/kg) at 60, 90, and 120 min interval on OGTT. The results for antioxidant potential indicate that at 100 mg/kg dose of combinatorial extract of curcumin significantly prevented the high-fat diet and low-dose streptozotocin-induced changes in the oxidative stress parameters (P < 0.01) which supports popular medicinal uses of this combinatorial extract as antihyperglycemic and hypolipidemic and is likely to bring this promising natural product to the forefront of therapeutic agents in the in the treatment of “metabolic syndrome”

Celiac disease: Role of genetics and immunity and update on novel strategies for treatment

Celiac disease (CD) is one of the most common inflammatory diseases of the small intestine which causes abdominal pain, diarrhoea, malabsorption, weight loss, anorexia, and iron deficiency anaemia in humans. It is a human leukocyte antigen (HLA)-linked disorder that is triggered by the gluten and gliadin proteins from wheat and related cereals. The presence of other genetic factors such as HLA-DQ2 and HLA-DQ8 have also been identified for the generation of circulating autoantibodies to the enzyme transglutaminase (TG2). The TG2 enzyme deamidates the gluten peptides and increases their affinity for the HLA-DQ2 or HLA-DQ8, which in turn cause a more vigorous activation of CD4+ T-helper 1 (Th1) cells and trigger the immune response, and such immune cascade eventually leads to intestinal membrane damage and malabsorption. Generally, CD is managed by lifelong gluten-free diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Several pharmacological agents and alternative therapies for treating CD are currently under development and are in clinical trials, The purpose of this review is to highlight the complex involvement of genetics and immunity in CD and to focus on the novel strategies being used for developing adjunct and alternative therapies for the treatment of CD.Biomedical Reviews 2014; 25: 45-58

Lactose intolerance: genetics of lactase polymorphisms, diagnosis and novel therapy

Lactose intolerance is a common disorder affecting an individual's ability to digest lactose present in milk or any food product. Lactose intolerance is caused by the deficiency of β-galactosidase (lactase) in the digestive tract. Diagnosis of lactose intolerance is not so simple and straightforward clinically. Many biochemical and genetic tests have been developed for the determination of lactose intolerance. Several case reports indicate wherein subjects have self-diagnosed being lactose intolerant. There is an emerging link of this disorder with human gene polymorphism, where genetic basis has been used as a diagnostic tool. The high prevalence of this condition among children and adults has compelled the production of lactose-free foods. Additionally, external enzyme supplementation has been looked at as an alternative protective mechanism in lactose intolerant subjects. This review highlights the genetic variants of lactase polymorphism and theranostic (therapeutic and diagnostic) strategies for lactose intolerance.Biomedical Reviews 2014; 25: 35-44

The impact of antioxidant diets, nutraceuticals and physical activity interventions in the prevention of cardiometabolic diseases: An overview

Hippocrates - Father of Medicine (ca 460-370 BC) - endorsed the cuative effects of foods; he said: "Leave your drugs in the chemist's pot if you can heal the patient with food". This review focuses on the management of cardio-metabolic diseases (CMDs) with nutraceuticals and antioxidant diets such as Allium sativum, turmeric, soybean, peptides, phytosterols, resveratrol, polyphenolic substances etc. CMDs are a cluster of conditions linked to altered fat and carbohydrate metabolism as well as macroand micro-vascular problems. CMDs cause severe pathophysiological and metabolic alterations in the body, resulting in the occurrence of chronic diseases like atherosclerosis, coronary heart disease and stroke, neurodegenerative ailments, fatty liver, kidney malfunction, hypercholesterolaemia, hyperlipidaemia, insulin resi-tance and some cancers, consequently imposing a very high economic burden on the healthcare costs. Currently used pharmacotherapies are not only expensive but also are associated with undesirable adverse events. Thus, there is an urgent need for affordable, cost-effective and alternative safe therapies for the prevention and management of CMDs. Holistic approaches targeted for health promotion and prevention of CMDs include the intake of antioxidant-rich diets, anti-inflammation wholesome foods and moderate physical activity (about 30 min/day). Such strategies will not only prevent obesity-related CMDs, type 2 diabetes mellitus (T2DM), coronary heart disease and stroke, but also will improve the quality of patient's life and consequently reduce healthcare burdens. Nutraceuticals and probiotics exhibit anti-inflammation, anti-aging, anti-obesity and anti-diabetic effects, thereby reducing the adverse health risks associated with CMDs. Antioxidants protect cell membranes and DNA from excessive free radicals, which contribute to CMD related diseases. Physical exercise along with dietary interventions helps to mitigate oxidative stress, improve blood triglyceride levels, increase HDL-cholesterol and reduce LDLcholesterol and reverse the biological markers associated with CMDs. Many studies have provided robust scientific evidence and demonstrated links between dietary interventions, nutraceuticals, probiotics, wholesome foods and physical activity for the prevention of CMDs. The major limitations in promoting nonpharmacological therapies for health and well-being benefits are a lack of public awareness and a paucity of clinical nutrition instruction for medical students on the merits of complementary methods for the prevention and management of CMDs. The goals of this review are to provide up-to-date knowledge about selected nutraceuticals, wholesome foods and physical activity in the prevention of CMDs and the underlying mechanisms associated with each intervention, which will ultimately improve patient's quality of life and assist in reducing healthcare costs globally

CB2 receptor agonist and L- arginine combination attenuates diabetic cardiomyopathy in rats via NF-ĸβ inhibition

Beta-caryophyllene (BCP), a cannabinoid 2 receptor (CB2) agonist has recently been found to have cardioprotective activity as an anti-inflammatory and antioxidant molecule. L-arginine (LA), a nitric oxide (NO) donor is a potential regulator of cardiovascular function. Considering the role of CB2 receptor activation and NO regulation in cardiovascular diseases, the combination of BCP with LA may be a possible treatment of diabetic cardiomyopathy (DCM). Hence, we investigated the efficacy of the novel combination of BCP with LA on cardiovascular inflammation and oxidative stress in diabetic rats. DCM was induced by Streptozotocin (55 mg/kg) in SD rats intraperitoneally. BCP, LA and BCP with LA were administered to diabetic rats for 4 weeks. After completion of the study, hemodynamic parameters, biochemical parameters, and inflammatory cytokine levels were analyzed. Also, oxidative stress parameters, NF-ĸβ expression and histopathology in cardiac tissues were estimated. The combination of BCP (200 mg/kg) with LA (200 mg/kg) significantly normalized the hemodynamic parameters and decreased the glucose, cardiac markers, IL-6 and TNF-α levels. Treatment of BCP and LA showed a significant decrease in oxidative stress and down-regulated the cardiac expression of NF-ĸβ. Thus, the combination of BCP with LA improves cardiac functions by attenuating inflammation through NF-ĸβ inhibition in DCM.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Therapeutic roles of antioxidant and nutraceuticals in the prevention and management of Alzheimer’s disease: A systematic review

Alzheimer’s disease (AD) has emerged as a serious and challenging neurological disorder in the ageing population worldwide. The progressive decline of mental health in AD patients causes memory loss, cognition decline, and motor impairment, which impacts adversely on the quality of life of afflicted individuls. Health care costs of mental diseases, dementia and AD are escalating globally, because the AD patients need continuous attention either by the family members or by the health care providers. Also, pharmaceutical treatment and hospital cost of AD is very expensive for the society. Therefore,  there is an urgent need to develop cost-effective, affordable, and safe alternative remedies for the prevention/mitigation and management of AD. Plant-derived anti-oxidant/anti-inflammation macromolecules (e.g., curcumin, genistein, melatonin, resveratrol, vanillic acid, caffeic acid, berberine) and nutraceuticals (Gingko Biloba) appear to be the safer and cost-effective promising options for the prevention/progression and management of AD patients. The underlying causes and pathological mechanisms of AD are multiple and complex, which include genetic, epigenetic, non-genetic and environmental risk factors. Lifestyle aspects (e.g., excessive tobacco smoking and alcohol abuse), unhealthy dietary habits, accumulation of heavy metals (arsenic, lead, cobalt, mercury) in CNS, and chronic viral infections are considered some other risk factors in memory loss and AD. Brain has relatively low levels of antioxidants and low repair capacity of neuronal cells. Reduced blood supply and impaired mitochondria promote lesser ATP synthesis and energy support in the brain. Many studies have suggested that excessive oxidative stress in the brain leads to the overproduction of free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS) from mitochondrial damage and reduction of ATP synthesis. The unabated over production of ROS/RNS cause insults to brain lipids by intiating lipid peroxidation and damage to cellular molecules, resulting in pathological injury and neuronal death. Antioxidant and anti-inflammation phytomolecules, dietary flavonoids, and nutraceuticals have gained significant importance for scavenging the free radicals and producing neuro-protective and memory-enhancing effects. Systematic searches were done using PUBMED, EMBASE, Scopus, Google Scholar, ResearchGate, and Web of Science databases. Numerous in vitro and in vivo studies have demonstrated that dietary antioxidant/anti-inflammation flavonoids, micronutrients (vitamins, trace metals, amino acids), and plant-derived polyphenols synergistically exhibit neuroprotective activity in AD animal models by stimulating transcription of the endogenous antioxidant system in the brain. The aims and objectives of this review are to recapitulate the current knowledge about the pathophysiology of AD and to shed light on the therapeutic strategies being used for slowing down the progression of dementia and cognitive decline.  We will also provide an overview of the proposed underlying mechanisms of different neutraceuticals and their recommended dosages in the prevention/mitigation of AD along with a summary of the antioxidant/anti-inflammation ingredients present in patented formulations