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Diabetes and Obesity International Journal


Citation: Mahmoud AM and Hussein OE. Anti-Diabetic Effect of Naringin: Insights into the Molecular Mechanism. Diabetes Obes Int J 2016, 1(5): 000128.

Anti-Diabetic Effect of Naringin: Insights into the Molecular Mechanism

Mahmoud AM1,2* and Hussein OE1
1Department of Zoology, Faculty of Science, Beni-Suef University, Egypt
22Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Germany
Editorial
Volume 1 Issue 5 - 2016
Received Date: : September 26, 2016
Published Date: September 29, 2016

*Corresponding author: Ayman M Mahmoud, Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Salah Salim St., 62514, Beni-Suef, Egypt. Tel: +201144168280; Email: ayman.mahmoud@science.bsu.edu.eg

Full Text
Editorial

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia resulting from either defect in insulin secretion or insulin action [1,2]. In 2015, the International Diabetes Federation (IDF) anticipated that the number of diabetes patients was 415 million and is expected to increase to 642 million by 2040 [3]. If ineffectively controlled, chronic hyperglycemia can cause numerous complications in different body organs [3]. Because of the limitations and side effects of the current therapeutic options for the management of diabetes, the search for safe and effective alternative anti-diabetic agents became a necessity.

Flavonoids are a group of natural polyphenolic compounds with potential benefits in human health [4]. Research from our laboratory showed significant antioxidant, anti-inflammatory, anti-diabetic, cardioprotective and hepatoprotective effects of flavonoids [2,5-10]. Naringin and its aglycone naringenin are two flavonoid compounds with promising anti-diabetic effects. We have previously reported the potent anti-diabetic effects of naringin, both in vivo and in vitro [2,6,9]. In our studies, we have demonstrated the ability of naringin to improve blood glucose levels through its ability to improve insulin sensitivity and secretion, attenuate inflammation and oxidative stress, enhance peripheral glucose uptake, decrease intestinal glucose and cholesterol absorption and suppress hepatic glucose production. In addition, naringin showed marked modulatory effect on adiponectin and resist in levels, adipose tissue peroxisome proliferator activated receptor gamma (PPARγ) expression, and muscle glucose transporter (GLUT)-4 translocation [9,11,12].

In other studies, naringin showed ability to decrease the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase and thus decrease blood lipids [12- 14]. Naringin has also been reported to regulate the plasma lipids in hypercholesterolemic animals fed a high fat diet [15,16]. In the liver of db/db mice, naringin modified the activities of hepatic lipid-metabolizing enzymes and improved plasma lipid metabolism [16]. In Type 2 diabetic mice, naringin up-regulated hepatic PPARγ and GLUT4, and regulated the expression of hepatic enzymes involved in glycolysis and gluconeogenesis, thereby improving hyperglycemia [16,17]. In hypercholesterolemic individuals, daily consumption of naringin suppressed the biosynthesis of hepatic cholesterol and decreased plasma low-density lipoprotein (LDL)-cholesterol [15]. These findings supporting the notion that naringin may play a vital role in preventing diabetes as well as obesity.

Taken together, naringin is an effective biomolecule that can play a promising role in treating diabetes and its complications. Naringin showed marked modulatory effects on insulin sensitivity and secretion, glucose transporters, PPARγ, hepatic glucose production, peripheral glucose uptake, blood lipids, cholesterol biosynthesis, intestinal glucose absorption, oxidative stress and inflammation (summarized mechanistic pathways are represented in Figure 1). No doubt that there are other beneficial effects to consider; therefore, additional studies are needed to promote our understanding of the exact mechanistic pathways mediating the anti-diabetic effect of naringin.

Abbreviations

AMPK, 5' adenosine monophosphateactivated protein kinase; GLUT, glucose transporter; LPL, lipoprotein lipase; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; G6PD, glucose-6-phosphate dehydrogenase; PEPCK, phosphoenolpyruvate carboxykinase; G6Pase, glucose 6-phosphatase; PPARγ, peroxisome proliferator activated receptor gamma; NF- κB, nuclear factor-kappaB; TNF-α, tumor necrosis factor alpha; IL, interleukin; LPO, lipid peroxidation; NO, nitric oxide; GSH, reduced glutathione; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase.

References
  1. American Diabetes Association (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33(S1): S62-S69.
  2. Mahmoud AM, Ashour MB, Abdel-Moneim A, Ahmed OM (2012) Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats. J Diabetes Complications 26(6): 483-490.
  3. International Diabetes Federation (2015) IDF Diabetes Atlas 7th (edn) Brussels, Belgium.
  4. Barnes S, Prasain J (2005) Current progress in the use of traditional medicines and nutraceuticals. Curr Opin Plant Biol 8(3): 324-328.
  5. Mahmoud AM (2012) Influence of rutin on biochemical alterations in hy-perammonemia in rats. Exp Toxicol Pathol 64(7-8): 783-789.
  6. Mahmoud AM (2013) Hematological alterations in diabetic rats; role of adipocytokines and effect of citrus flavonoids. EXCLI J 12: 647-657.
  7. Mahmoud AM, Soliman AS (2013) Rutin attenuates hyperlipidemia and cardiac oxidative stress in diabetic rats. Egypt J Med Sci 34: 287-302.
  8. Mahmoud AM (2014) Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation. Can J Physiol Pharmacol 92(9): 717-724.
  9. Mahmoud AM, Ahmed OM, Ashour MB, AbdelMoneimA (2015) In vivo and in vitro antidiabetic effects of citrus flavonoids; a study on the mechanism of action. Int J Diabetes Dev Ctries 35(3): 250-263.
  10. Kamel EM, Mahmoud AM, Ahmed SA, Lamsabhi AM (2016) A phytochemical and computational study on flavonoids isolated from Trifoliumresupinatum L. and their novel hepatoprotective activity. Food Funct 7(4): 2094-2106.
  11. Mahmoud AM, Ahmed OM, Abdel-Moneim A, Ashour MB (2013) Up regulation of PPARγ mediates the antidiabetic effects of citrus flavonoids in high fat diet fed-streptozotocin induced type 2 diabetic rats. Int J Bioassays 2(5): 756-761.
  12. Ahmed OM, Mahmoud AM, Abdel-Moneim A, Ashour MB (2012) Antidiabetic effects of hesperidin and naringin in type 2 diabetic rats. Diabetol Croat 41(2): 53-67.
  13. Lee SH, Park YB, Bae KH, Kwon YK, Bok SH, et al. (1999) Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase and acyl coenzyme A: Cholesterol acyltransferase in rats. Ann Nutr Metab 43: 173-180.
  14. Bok SH, Lee SH, Park YB, Bae KH, Son KH, et al. (1999) Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA: Cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J Nutr 129(6): 1182-1185.
  15. Jung UJ, Kim HJ, Lee JS, Lee MK, Kim HO, et al. (2003) Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects. Clin Nutr 22(6): 561- 568.
  16. Jung UJ, Lee MK, Park YB, Kang MA, Choi MS (2006) Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int J Biochem Cell Biol 38(7): 1134- 1145.
  17. Pu P, Gao DM, Mohamed S, Chen J, Zhang J, et al. (2012) Naringin ameliorates metabolic syndrome by activating amp-activated protein kinase in mice fed a high-fat diet. Arch Biochem Biophys 518(1): 61-70.
Figure 1

Figure 1: Schematic presentation of the anti-diabetic mechanism of naringin.

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