Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice.

SCOPE Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. METHODS AND RESULTS C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. CONCLUSION Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.

[1]  Alan D. Lopez,et al.  Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2014, The Lancet.

[2]  I. Raskin,et al.  Stable, water extractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro. , 2014, Phytochemistry.

[3]  Michael J. MacDonald,et al.  Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase , 2014, Nature.

[4]  D. Ribnicky,et al.  Artemisia scoparia Enhances Adipocyte Development and Endocrine Function In Vitro and Enhances Insulin Action In Vivo , 2014, PloS one.

[5]  M. Lombès,et al.  Metformin Lowers Plasma Triglycerides by Promoting VLDL-Triglyceride Clearance by Brown Adipose Tissue in Mice , 2014, Diabetes.

[6]  G. Rena,et al.  Molecular mechanism of action of metformin: old or new insights? , 2013, Diabetologia.

[7]  F. Azizi,et al.  Potential efficacy of broccoli sprouts as a unique supplement for management of type 2 diabetes and its complications. , 2013, Journal of medicinal food.

[8]  I. Raskin,et al.  In vivo and in vitro antidiabetic effects of aqueous cinnamon extract and cinnamon polyphenol-enhanced food matrix. , 2012, Food chemistry.

[9]  H. Katagiri,et al.  Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. , 2012, Cell metabolism.

[10]  F. Azizi,et al.  Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial , 2012, International journal of food sciences and nutrition.

[11]  F. Azizi,et al.  Effects of broccoli sprout with high sulforaphane concentration on inflammatory markers in type 2 diabetic patients: A randomized double-blind placebo-controlled clinical trial , 2012 .

[12]  P. Shetty Public health: India's diabetes time bomb , 2012, Nature.

[13]  M. Mbikay Therapeutic Potential of Moringa oleifera Leaves in Chronic Hyperglycemia and Dyslipidemia: A Review , 2012, Front. Pharmacol..

[14]  D. Ribnicky,et al.  Bioactives from bitter melon enhance insulin signaling and modulate acyl carnitine content in skeletal muscle in high-fat diet-fed mice. , 2011, The Journal of nutritional biochemistry.

[15]  Z. Dvořák,et al.  Rifampicin Does not Significantly Affect the Expression of Small Heterodimer Partner in Primary Human Hepatocytes , 2011, Front. Pharmacol..

[16]  J. Pezzuto,et al.  Inhibition of Lipopolysaccharide-Induced Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression by 4-[(2′-O-acetyl-α-L-Rhamnosyloxy)Benzyl]Isothiocyanate from Moringa oleifera , 2011, Nutrition and cancer.

[17]  D. Mashek,et al.  Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning , 2011, Hepatology.

[18]  Qipeng Yuan,et al.  Preparation and stability investigation of the inclusion complex of sulforaphane with hydroxypropyl-β-cyclodextrin , 2010 .

[19]  J. Pezzuto,et al.  Potential anti-inflammatory phenolic glycosides from the medicinal plant Moringa oleifera fruits. , 2010, Bioorganic & medicinal chemistry.

[20]  M. D’Incalci,et al.  The isothiocyanate produced from glucomoringin inhibits NF-kB and reduces myeloma growth in nude mice in vivo. , 2010, Biochemical pharmacology.

[21]  M. Roller,et al.  Contribution of chlorogenic acids to the inhibition of human hepatic glucose-6-phosphatase activity in vitro by Svetol, a standardized decaffeinated green coffee extract. , 2010, Journal of agricultural and food chemistry.

[22]  R. Kubant,et al.  Leptin-induced endothelial dysfunction in obesity. , 2008, American journal of physiology. Heart and circulatory physiology.

[23]  Chung S. Yang,et al.  The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice. , 2008, The Journal of nutrition.

[24]  K. Becker,et al.  Adipocyte gene expression is altered in formerly obese mice and as a function of diet composition. , 2008, The Journal of nutrition.

[25]  Thomas D. Schmittgen,et al.  Analyzing real-time PCR data by the comparative CT method , 2008, Nature Protocols.

[26]  L. Heilbronn,et al.  Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes , 2007, Diabetes.

[27]  M. Ndong,et al.  Effects of Oral Administration of Moringa oleifera Lam on Glucose Tolerance in Goto-Kakizaki and Wistar Rats , 2007, Journal of clinical biochemistry and nutrition.

[28]  David E. Williams,et al.  Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. , 2007, Pharmacological research.

[29]  D. Langin Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. , 2006, Pharmacological Research.

[30]  P. Ramarao,et al.  Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. , 2005, Pharmacological research.

[31]  J. Agudo,et al.  Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance , 2003, Diabetologia.

[32]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002, The New England journal of medicine.

[33]  T. Shapiro,et al.  Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[34]  M. Lazar,et al.  The hormone resistin links obesity to diabetes , 2001, Nature.

[35]  K. Petersen,et al.  Mechanism by which metformin reduces glucose production in type 2 diabetes. , 2000, Diabetes.

[36]  D. Moller Potential Role of TNF-α in the Pathogenesis of Insulin Resistance and Type 2 Diabetes , 2000, Trends in Endocrinology & Metabolism.

[37]  S. Chua,et al.  Obesity and diabetes in TNF-alpha receptor- deficient mice. , 1998, The Journal of clinical investigation.

[38]  K. Uysal,et al.  Protection from obesity-induced insulin resistance in mice lacking TNF-α function , 1997, Nature.

[39]  R. Holman,et al.  UKPDS 20: plasma leptin, obesity, and plasma insulin in type 2 diabetic subjects. , 1997, The Journal of clinical endocrinology and metabolism.

[40]  R. Goldbohm,et al.  Epidemiological studies on brassica vegetables and cancer risk. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[41]  A. Gilani,et al.  Isolation and structure elucidation of new nitrile and mustard oil glycosides from Moringa oleifera and their effect on blood pressure. , 1994, Journal of natural products.

[42]  B. Spiegelman,et al.  Tumor necrosis factor alpha inhibits signaling from the insulin receptor. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[43]  L. Pénicaud,et al.  Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. , 1992, Journal of cell science.

[44]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[45]  J. Folch,et al.  A simple method for the isolation and purification of total lipides from animal tissues. , 1957, The Journal of biological chemistry.

[46]  R. Mithen,et al.  Glucosinolates, isothiocyanates and human health , 2008, Phytochemistry Reviews.

[47]  N. Unwin,et al.  Diabetes in sub-Saharan Africa. , 2001, Advances in experimental medicine and biology.

[48]  D. Moller Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. , 2000, Trends in endocrinology and metabolism: TEM.

[49]  K. Uysal,et al.  Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. , 1997, Nature.

[50]  Mol Nutr Food Res,et al.  Bog blueberry anthocyanins alleviate photoaging in ultraviolet-B irradiation-induced human dermal fibroblasts , 2022 .