naphthoquinones and Obesity

Diabetes mellitus is the seventh leading cause of death globally. Ninety percent of the diabetic population suffers from type-2 diabetes, which still needs an effective, safe and economical oral hypoglycemic therapy. Plants are rich sources of various therapeutic molecules. More than 400 medicinal plants of interesting phytochemical diversity have been reported for their antidiabetic potential. Naphthoquinones are a group of phytochemicals, which have a wide range of pharmacological potential, including antidiabetic activity. Naphthoquinones exert their antidiabetic effects through various mechanisms such as the inhibition of α-glucosidase and protein tyrosine phosphatase 1B, increased glucose uptake in myocytes and adipocytes via glucose transporter type 4 (GLUT4) and GLUT2 translocations, enhanced peroxisome proliferator-activated receptor gamma (PPARγ) ligand activity, and by normalizing carbohydrate metabolizing enzymes in the liver. Moreover, naphthoquinone inhibits adipogenesis by both upstream and downstream regulation to control obesity, which is one of the important risk factors for diabetes. Naturally occurring naphthoquinones, as well as their plant sources, are therefore of interest for exploring their antidiabetic potential. The present review aims to overview the antidiabetic potential of naphthoquinones and their plant resources in Thailand.

Topics: Adipogenesis; alpha-Glucosidases; Animals; Diabetes Mellitus; Enzyme Inhibitors; Humans; Hypoglycemic Agents; Naphthoquinones; Obesity; Plant Extracts; Plants, Medicinal; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Thailand

Chronic consumption of fructose causes obesity and nonalcoholic fatty liver disease (NAFLD). Currently available therapies have limitations; hence there is a need to screen new molecules. Plumbagin is a naphthoquinone present in the roots of Plumbago species which has hypolipidemic and hepatoprotective activities.. Rats were divided into five groups: normal control, disease control, orlistat, plumbagin (0.5 mg/kg and 1 mg/kg body weight). The normal control group received standard diet and drinking water while the remaining groups received fructose in drinking water alongwith the standard diet for 16 weeks. Orlistat and plumbagin were administered orally from the 9. Fructose feeding resulted in a significant increase in the body weight gain, calorie intake, visceral fat, liver weight, blood glucose and insulin and caused dyslipidemia which was mitigated by plumbagin. Plumbagin exerted antioxidant, anti-inflammatory and anti-fibrotic effects in the liver and reduced the hepatic lipids. Plumbagin reduced the gene expression of SREBP-1c and increased that of PPAR-α. Plumbagin reduced the hypertrophy of adipocytes and ameliorated the degenerative changes in the liver.. Plumbagin thus seems to be a promising molecule for the management of obesity and NAFLD.

Topics: Adjuvants, Immunologic; Animals; Antioxidants; Fructose; Inflammation; Lipid Metabolism; Male; Naphthoquinones; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Random Allocation; Rats; Rats, Wistar

Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Differentiation; Humans; Kinetics; Lipase; Male; Mice; Molecular Docking Simulation; Naphthoquinones; Obesity; Plant Roots; Plumbaginaceae; Rats; Rats, Wistar; Triglycerides

There has been great interest in the browning of fat for the treatment of obesity. Although β-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose tissue (WAT), increased the expression of brown adipocyte-specific genes (e.g., uncoupling protein 1 [UCP1]), decreased body weight gain, and ameliorated metabolic parameters in mice fed a high-fat diet. Consistently, BLC-treated mice showed significantly higher energy expenditure compared with control mice. In vitro, BLC increased the expression of brown adipocyte-specific genes in stromal vascular fraction-differentiated adipocytes. BLC also controlled the expression of miR-382, which led to the upregulation of its direct target, Dio2. Upregulation of miR-382 markedly inhibited the differentiation of adipocytes into beige adipocytes, whereas BLC recovered beige adipocyte differentiation and increased the expression of Dio2 and UCP1. Our findings suggest that the BLC-mediated increase in the browning of WAT and the thermogenic capacity of BAT significantly results in increases in energy expenditure. Browning of WAT by BLC was partially controlled via the regulation of miR-382 targeting Dio2 and may lead to the prevention of diet-induced obesity.

Topics: Adipocytes; Adipocytes, Brown; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Calorimetry, Indirect; Cells, Cultured; Diet, High-Fat; Energy Metabolism; Gene Expression Regulation; Glucose Tolerance Test; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Naphthoquinones; Obesity; Oxygen Consumption; Thermogenesis

Obesity represents a major public health problem, and identifying natural compounds that modulate energy balance and glucose homeostasis is of interest for combating obesity and its associated disorders. The naphthoquinone shikonin has diverse beneficial properties including anti-inflammatory, anti-oxidant, and anti-microbial effects. The objective of this study is to investigate the effects of shikonin on adiposity and glucose homeostasis.. The metabolic effects of shikonin treatment on mice fed regular chow or challenged with a high-fat diet (HFD) were determined.. Shikonin treated mice fed regular chow exhibited improved glucose tolerance compared with controls. In addition, shikonin treated mice fed HFD displayed decreased weight gain and resistance to HFD-induced glucose intolerance. Further, shikonin treatment decreased HFD-induced hepatic dyslipidemia. These findings correlated with enhanced hepatic insulin signaling in shikonin treated mice as evidenced by increased tyrosyl phosphorylation of the insulin receptor and enhanced downstream signaling.. These studies identify shikonin as a potential regulator of systemic glucose tolerance, energy balance, and adiposity in vivo.

Topics: Adiposity; Animals; Diet, High-Fat; Down-Regulation; Drugs, Chinese Herbal; Energy Metabolism; Glucose; Glucose Intolerance; Glucose Tolerance Test; Homeostasis; Insulin; Insulin Resistance; Liver; Male; Mice; Mice, Inbred C57BL; Naphthoquinones; Obesity; Weight Gain

Nicotinamide adenine dinucleotides (NAD+ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD+-to-NADH ratio is implicated in metabolic syndrome. However, it is still unknown whether a modulating intracellular NAD+-to-NADH ratio is beneficial in treating metabolic syndrome. We tried to determine whether pharmacological stimulation of NADH oxidation provides therapeutic effects in rodent models of metabolic syndrome.. We used beta-lapachone (betaL), a natural substrate of NADH:quinone oxidoreductase 1 (NQO1), to stimulate NADH oxidation. The betaL-induced pharmacological effect on cellular energy metabolism was evaluated in cells derived from NQO1-deficient mice. In vivo therapeutic effects of betaL on metabolic syndrome were examined in diet-induced obesity (DIO) and ob/ob mice.. NQO1-dependent NADH oxidation by betaL strongly provoked mitochondrial fatty acid oxidation in vitro and in vivo. These effects were accompanied by activation of AMP-activated protein kinase and carnitine palmitoyltransferase and suppression of acetyl-coenzyme A (CoA) carboxylase activity. Consistently, systemic betaL administration in rodent models of metabolic syndrome dramatically ameliorated their key symptoms such as increased adiposity, glucose intolerance, dyslipidemia, and fatty liver. The treated mice also showed higher expressions of the genes related to mitochondrial energy metabolism (PPARgamma coactivator-1alpha, nuclear respiratory factor-1) and caloric restriction (Sirt1) consistent with the increased mitochondrial biogenesis and energy expenditure.. Pharmacological activation of NADH oxidation by NQO1 resolves obesity and related phenotypes in mice, opening the possibility that it may provide the basis for a new therapy for the treatment of metabolic syndrome.

Topics: Adenylate Kinase; Animals; Disease Models, Animal; Energy Metabolism; Metabolic Syndrome; Mice; Mice, Knockout; NAD; NAD(P)H Dehydrogenase (Quinone); NADPH Dehydrogenase; Naphthoquinones; Obesity; Oxidation-Reduction; Phenotype; Signal Transduction