Volume 26, Issue 1 (March 2022)                   Physiol Pharmacol 2022, 26(1): 20-29 | Back to browse issues page

XML Print

Abstract:   (1334 Views)
Introduction: Psychomotor slowing and reduced mental flexibility are symptoms of cognitive decline that can occur in type 2 diabetes disease (TD2). Strategies that combine the control of hyperglycaemia with prevention of cognitive decline are desirable. Thus, this study reports the effect of naringin on cognitive deficit in diabetic rats. Methods: TD2 in Wistar rats was induced with nicotinamide/streptozotocin (NA/STZ). Naringin (50 and 100 mg/kg) or glibenclamide (5mg/kg) was administered for 30 days to diabetic rats. Cognitive performance was investigated using the Morris water maze. Serum glucose, lipid profiles, brain tumour necrosis factor alpha (TNF-α) and acetylcholinesterase (AChE) activity were determined. Results: Naringin and glibenclamide significantly reduced the escape latency, increased the time spent in the correct quadrant and number of entries in diabetic rats. Also, naringin reduced blood glucose, serum cholesterol, low-density lipoprotein cholesterol levels, triglycerides and prevented a decrease in the level of high-density lipoprotein cholesterol, in diabetic rats. Naringin and glibenclamide treated diabetic rats showed a significant low levels of AChE activity and TNF-α. Conclusion: Naringin ameliorates diabetes induced cognitive deficit via reduction of inflammation, hyperglycemia, hyperlipidaemia and AChE activity
Full-Text [PDF 886 kb]   (441 Downloads)    

1. Adil M, Visnagri A, Kumar VS, Kandhare AD, Ghosh P, Bodhankar S. Protective effect of naringin on sodium arsenite induced testicular toxicity via modulation of biochemical perturbations in experimental rats. Pharmacologia 2014; 5: 222-34. [DOI:10.5567/pharmacologia.2014.222.234]
2. Ahmad W, Singh S, Kumar S. Phytochemical screening and antimicrobial study of Euphorbia hirta extracts. J Med Plants Stud 2017; 5: 183-86.
3. Ahmed OM, Hassan MA, Abdel-Twab S M, Azeem MN. Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats. Biomed Pharmacother 2017; 94: 197-205. [DOI:10.1016/j.biopha.2017.07.094]
4. Baynes HW. Classification, pathophysiology, diagnosis and management of diabetes mellitus. J diabetes metab 2015; 6: 1-9.
5. Benavente-Garcia O, Castillo J. Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem 2008; 56: 6185-205. [DOI:10.1021/jf8006568]
6. Biessels G, Kappelle L. Utrecht Diabetic Encephalopathy Study G. Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology. Biochem Soc Trans 2005; 33: 1041-4. [DOI:10.1042/BST0331041]
7. Bok SH, Shin YW, Bae KH, Jeong TS, Kwon YK, Park YB, et al. Effects of naringin and lovastatin on plasma and hepatic lipids in high-fat and high-cholesterol fed rats. Nutr Res 2000; 20: 1007-15. [DOI:10.1016/S0271-5317(00)00191-3]
8. Brands MW, Bell TD, Gibson B. Nitric oxide may prevent hypertension early in diabetes by counteracting renal actions of superoxide. Hypertension 2004; 43: 57-63. [DOI:10.1161/01.HYP.0000104524.25807.EE]
9. Bromley-Brits K, Deng Y, Song W. Morris water maze test for learning and memory deficits in Alzheimer's disease model mice. J Vis Exp 2011; 53: e2920. [DOI:10.3791/2920]
10. Carvajal FJ, Inestrosa NC. Interactions of AChE with Aβ aggregates in Alzheimer's brain: therapeutic relevance of IDN 5706. Front Mol Neurosci 2011; 4: 19. [DOI:10.3389/fnmol.2011.00019]
11. Chen F, Zhang N, Ma X, Huang T, Shao Y, Wu C, et al. Naringin alleviates diabetic kidney disease through inhibiting oxidative stress and inflammatory reaction. Plos One 2015; 10: e0143868. [DOI:10.1371/journal.pone.0143868]
12. Chen Y, Nie YC, Luo YL, Lin F, Zheng YF, Cheng GH, et al. Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice. Food Chem Toxicol 2013; 58: 133-40. [DOI:10.1016/j.fct.2013.04.024]
13. Choe SC, Kim HS, Jeong TS, Bok SH, Park YB. Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 2001; 38: 947-55. [DOI:10.1097/00005344-200112000-00017]
14. Craft S, Cholerton B, Baker LD. Insulin and Alzheimer's disease: untangling the web. J Alzheimers Dis 2013; 33: 263-75. [DOI:10.3233/JAD-2012-129042]
15. Dodel R, Rominger A, Bartenstein P, Barkhof F, Blennow K, Förster S, et al. Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol 2013; 12: 233-43. [DOI:10.1016/S1474-4422(13)70014-0]
16. Duarte JM. Metabolic alterations associated to brain dysfunction in diabetes. Aging Dis 2015; 6: 304-21. [DOI:10.14336/AD.2014.1104]
17. Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88-95. [DOI:10.1016/0006-2952(61)90145-9]
18. Friedwald W, Leve R, Fredrichson D. Estimation of concentration of low density lipoproteins separated by three different methods. Clin Chem 1972; 18: 499-502. [DOI:10.1093/clinchem/18.6.499]
19. Haam J, Yakel JL. Cholinergic modulation of the hippocampal region and memory function. J Neurochem 2017; 142: 111-21. [DOI:10.1111/jnc.14052]
20. Jung UJ, Lee MK, Jeong KS, Choi MS. The hypoglycemic effects of hesperidin and naringin are partly mediated by hepatic glucose-regulating enzymes in C57BL/KsJ-db/db mice. J Nutr 2004; 134: 2499-503. [DOI:10.1093/jn/134.10.2499]
21. Jung UJ, Lee MK, Park YB, Kang MA, Choi MS. Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int J Biochem Cell Biol 2006; 38: 1134-45. [DOI:10.1016/j.biocel.2005.12.002]
22. Kloppenborg RP, van den Berg E, Kappelle LJ, Biessels GJ. Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review. Eur J Pharmacol 2008; 585: 97-108. [DOI:10.1016/j.ejphar.2008.02.049]
23. Kopf SR, Baratti CM. Effects of posttraining administration of insulin on retention of a habituation response in mice: participation of a central cholinergic mechanism. Neurobiol Learn Mem 1999; 71: 50-61. [DOI:10.1006/nlme.1998.3831]
24. Lin CY, Ni CC, Yin MC, Lii CK. Flavonoids protect pancreatic beta-cells from cytokines mediated apoptosis through the activation of PI3-kinase pathway. Cytokine 2012; 59: 65-71. [DOI:10.1016/j.cyto.2012.04.011]
25. Liu X, Liu M, Mo Y, Peng H, Gong J, Li Z, et al. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Iran J Basic Med Sci 2016; 19: 417-22. [DOI:10.1007/s11011-015-9779-5]
26. Madsen PA, Bingham H, Liu H. A new Boussinesq method for fully nonlinear waves from shallow to deep water. J Fluid Mech 2002; 462: 1-33. [DOI:10.1017/S0022112002008467]
27. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998; 47: 224-29. [DOI:10.2337/diab.47.2.224]
28. Morris RG. Spatial localization does not require the presence of local cues. Learn Motiv 1981; 12: 239-60. [DOI:10.1016/0023-9690(81)90020-5]
29. Mushtaq M, Sultana B, Bhatti HN, Asgher M. Optimization of enzyme-assisted revalorization of sweet lime (Citrus limetta Risso) peel into phenolic antioxidants. BioResources 2014; 9: 6153- 65. [DOI:10.15376/biores.9.4.6153-6165]
30. Namas R, Ghuma A, Hermus L, Zamora R, Okonkwo D, Billiar T, et al. The acute inflammatory response in trauma/hemorrhage and traumatic brain injury: current state and emerging prospects. Libyan J Med 2009; 4: 97-103. [DOI:10.3402/ljm.v4i3.4824]
31. Owira PM, Ojewole JA. The grapefruit: an old wine in a new glass? Metabolic and cardiovascular perspectives. Cardiovasc J Afr 2010; 21: 280-85.
32. Pollack RM, Donath MY, LeRoith D, Leibowitz G. Anti-inflammatory agents in the treatment of diabetes and its vascular complications. Diabetes care 2016; 39: 244-252. [DOI:10.2337/dcS15-3015]
33. Rajadurai M, Prince PS. Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: an in vivo and in vitro study. Toxicology 2007; 232: 216-25. [DOI:10.1016/j.tox.2007.01.006]
34. Ribeiro IA, Ribeiro MH. Naringin and naringenin determination and control in grapefruit juice by a validated HPLC method. Food Control 2008; 19: 432-38. [DOI:10.1016/j.foodcont.2007.05.007]
35. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59-62. [DOI:10.1038/362059a0]
36. Saelens W, Cannoodt R, Todorov H, Saeys Y. A comparison of single-cell trajectory inference methods. Nat Biotechnol 2019; 37: 547-54. [DOI:10.1038/s41587-019-0071-9]
37. Sima AA. Encephalopathies: the emerging diabetic complications. Acta Diabetol 2010; 47: 279- 93. [DOI:10.1007/s00592-010-0218-0]
38. Singh D, Chopra K. The effect of naringin, a bioflavonoid on ischemia-reperfusion induced renal injury in rats. Pharmacol Res 2004; 50: 187-93. [DOI:10.1016/j.phrs.2004.01.007]
39. Stephens JM, Lee J, Pilch PF. Tumor necrosis factor-α-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem 1997; 272: 971-76. [DOI:10.1074/jbc.272.2.971]
40. Wang X, Liu H, Zhang Y, Li J, Teng X, Liu A, et al. Effects of isolated positive maternal thyroglobulin antibodies on brain development of offspring in an experimental autoimmune thyroiditis model. Thyroid 2015; 25: 551-8. [DOI:10.1089/thy.2014.0310]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.