naphthoquinones and Diabetes-Mellitus

Diabetes mellitus is the main reason of morbidity and mortality worldwide. In recent years great attention has been paid to bioactivity of natural products due to their potential pharmacological utilization. Echinochrome is a natural compound isolated from sea urchins and possesses many biological effects. The hypoglycemic activity of echinochrome reported in many recent experiments.. In our study, we tried to collect all the possible hypoglycemic mechanism of echinochrome.. The hypoglycemic effect of echinochrome involving four main pathways; regeneration of pancreas, decrease insulin resistant, increase insulin production and improve glucose homeostasis.

Topics: Animals; Antioxidants; Biomarkers; Blood Glucose; Cholinesterase Inhibitors; Diabetes Mellitus; Glucosephosphate Dehydrogenase; Heme Oxygenase-1; Hexokinase; Homeostasis; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Liver; Naphthoquinones; Pancreas; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphatidylinositol 3-Kinase; Regeneration; Signal Transduction

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

Diabetes is a complicated multifactorial disorder in which the patient generally observes polyphagia, polydipsia, and polyuria due to uncontrolled growth in blood sugar levels. For its management, the pharmaceutical industry is working day and night to find a better drug with no or least toxicity. That's why nowadays a more focused branch is to use herbal phytoconstituents for its prevention. Shikonin is a naphthoquinone natural dye that is isolated from the plants of the Boraginaceae family and has proven its role as an anti-cancer, anti-inflammatory, and anti-gonadotrophic agent. In our previous study, we have published its anti-diabetic action by inhibiting the enzyme protein tyrosine phosphatase 1B. In this study, we were more focused on finding out the role of Shikonin and its pharmacophores by inhibiting the action of aldose reductase (AR) enzyme. The study was conducted using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. The absorption, distribution, metabolism, excretion (ADME), and toxicity profile were also evaluated in this study. Along with all the computational biology parameters we also focused on the in vitro activity and kinetic study of inhibitory activity of Shikonin against aldose reductase.

Topics: Aldehyde Reductase; Diabetes Mellitus; Enzyme Inhibitors; Humans; Hypoglycemic Agents; Molecular Docking Simulation; Naphthoquinones

Diabetic cardiomyopathy (DC) is one of the major lethal complications in patients with diabetes mellitus (DM); however, no specific strategy for preventing or treating DC has been identified.. This study aimed to investigate the effects of β-lapachone (Lap), a natural compound that increases antioxidant activity in various tissues, on DC and explore the underlying mechanisms.. As an in vivo model, C57BL/6 mice were fed with the high-fat diet (HF) for 10 weeks to induce type 2 DM. Mice were fed Lap with the HF or after 5 weeks of HF treatment to investigate the protective effects of Lap against DC.. In the two in vivo models, Lap decreased heart weight, increased heart function, reduced oxidative stress, and elevated mitochondrial content under the HF. In the in vitro model, palmitic acid (PA) was used to mimic the effects of an HF on the differentiated-cardiomyoblast cell line H9c2. The results demonstrated that Lap reduced PA-induced ROS production by increasing the expression of antioxidant regulators and enzymes, inhibiting inflammation, increasing mitochondrial activity, and thus reducing cell damage. Via the use of specific inhibitors and siRNA, the protective effects of Lap were determined to be mediated mainly by NQO1, Sirt1 and mitochondrial activity.. Heart damage in DM is usually caused by excessive oxidative stress. This study showed that Lap can protect the heart from DC by upregulating antioxidant ability and mitochondrial activity in cardiomyocytes. Lap has the potential to serve as a novel therapeutic agent for both the prevention and treatment of DC.

Topics: Animals; Antioxidants; Diabetes Mellitus; Diabetic Cardiomyopathies; Mice; Mice, Inbred C57BL; Mitochondria; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Oxidative Stress

Pesticide exposure during fetal life can lead to low birth weight and is commonly observed in reproductive toxicology studies. Associations have also been found in low birth weight babies born from pesticide-exposed gardeners. Since low birth weight is also linked to metabolic disorders, it can be speculated that early life exposure to pesticides could increase the risk of becoming obese or developing diabetes later in life. We have analyzed potential long-term effects of gestational and lactational exposure to a low dose mixture of six pesticides that individually can cause low birth weight: Cyromazine, MCPB, Pirimicarb, Quinoclamine, Thiram, and Ziram. Exposed male offspring, who were smaller than controls, displayed some degree of catch-up growth. Insulin and glucagon regulation was not significantly affected, and analyses of liver and pancreas did not reveal obvious histopathological effects. Efforts towards identifying potential biomarkers of metabolic disease-risk did not result in any strong candidates, albeit leptin levels were altered in exposed animals. In fat tissues, the key genes Lep, Nmb and Nmbr were altered in high dosed offspring, and were differentially expressed between sexes. Our results suggest that early-life exposure to pesticides may contribute to the development of metabolic disorders later in life.

Topics: 2-Methyl-4-chlorophenoxyacetic Acid; Adipose Tissue; Animals; Butyrates; Carbamates; Diabetes Mellitus; Female; Fetal Growth Retardation; Infant, Low Birth Weight; Naphthoquinones; Pesticides; Pregnancy; Prenatal Exposure Delayed Effects; Pyrimidines; Rats; Rats, Wistar; Thiram; Triazines; Ziram

The current study was designed to investigate the protective role of alkannin (ALK) on liver injury in diabetic C57BL/KsJ-db/db mice and explore its potential mechanisms.. An oral glucose tolerance test (OGTT) was performed. The levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) were determined by commercial kits. The pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were determined by ELISA. The levels of the ROCK/NF-κB pathway were determined by Western blotting.. The contents of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were inhibited by ALK, metformin or fasudil in diabetic db/db mice. Further, Western blotting analysis showed that the expression of Rho, ROCK1, ROCK2, p-NF-κBp65, and p-IκBα was significantly reversed by ALK treatment. In human hepatic HepG2 cells, the hepatoprotective effects of ALK were further characterized. With response to palmitic acid-challenge, increased amounts of insulin, ALT, AST, TG, and TC were observed, whereas ALK pretreatment significantly inhibited their leakage in HepG2 cells without appreciable cytotoxic effects. The inflammation condition was recovered with ALK treatment as shown by changes of IL-1β, IL-6 and TNF-α. Further, Western blotting analysis also suggested that ALK improves hepatic inflammation in a Rho-kinase pathway.. The present study successfully investigated the role of Rho-kinase signalling in diabetic liver injury. ALK exhibited hepatoprotective effects in diabetic db/db mice, and it might act through improving hepatic inflammation through the Rho-kinase pathway.

Topics: Animals; Anti-Inflammatory Agents; Cell Survival; Cytokines; Diabetes Complications; Diabetes Mellitus; Hep G2 Cells; Humans; Inflammation; Liver; Liver Diseases; Mice, Inbred C57BL; Naphthoquinones; rho-Associated Kinases; Signal Transduction

Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.

Topics: Africa; Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Eating; Fatty Acids, Unsaturated; Hypoglycemic Agents; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Naphthoquinones; Plant Extracts; Plant Leaves; Plant Stems; Plants, Medicinal