Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-19T16:46:21.613Z Has data issue: false hasContentIssue false
  • English
  • Français

Antidepressant‐like effects of quercetin in diabetic rats are independent of hypothalamic–pituitary–adrenal axis

Published online by Cambridge University Press:  03 August 2015

Enver Ahmet Demir Open the ORCID record for Enver Ahmet Demir [Opens in a new window] ,
Hasan Serdar Gergerlioglu  and
Mehmet Oz
Enver Ahmet Demir*
Affiliation:
Department of Physiology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey
Hasan Serdar Gergerlioglu
Affiliation:
Department of Physiology, Faculty of Medicine, Selcuk University, Konya, Turkey
Mehmet Oz
Affiliation:
School of Health Services, Mevlana (Rumi) University, Konya, Turkey
*
Dr. Enver Ahmet Demir, Department of Physiology, Faculty of Medicine, Mustafa Kemal University, Hatay 31000, Turkey. Tel: +90 506 670 9515; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Quercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have benefits against diabetes and its complications. In the present study, we investigated effects of quercetin on depression-like behaviours and hypothalamic–pituitary–adrenal (HPA) axis in diabetic rats.

Methods

Experimental diabetes was induced by using streptozotocin, and either 50 or 100 mg/kg quercetin was intraperitoneally administered for 21 days. Following the last treatment, animals were subjected to the forced swim test, and subsequently, the blood was obtained by cardiac puncture to measure plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels.

Results

A significant increase of the total immobile time, accompanied by a decrease in the immobility latency, which suggests a depressive status, was observed in diabetic animals that was reversed by the treatment of 50 mg/kg quercetin. However, the higher dose of quercetin (100 mg/kg) was ineffective in alleviating depression-like behaviours. The plasma concentrations of ACTH, and total- and free-CORT were not affected by both doses of quercetin.

Conclusion

Therefore, we concluded that the antidepressant-like effects of quercetin in diabetes are independent of the HPA axis.

Keywords

adrenocorticotropic hormonecorticosteronedepressionexperimental diabetes mellitusquercetin
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 28 , Issue 1 , February 2016 , pp. 23 - 30
Check for updates
Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. International Diabetes Federation. IDF Diabetes Atlas: International Diabetes Federation; 2013. Available at http://www.idf.org/diabetesatlas. Accessed February 3, 2013.Google Scholar
2. Tripathi, BK, Srivastava, AK. Diabetes mellitus: complications and therapeutics. Med Sci Monit 2006;12:RA130–RA147.Google Scholar
3. Rubin, RR, Peyrot, M. Was Willis right? Thoughts on the interaction of depression and diabetes. Diabetes Metab Res Rev 2002;18:173–175.Google Scholar
4. Gois, C, Akiskal, H, Akiskal, K, Figueira, ML. Depressive temperament, distress, psychological adjustment and depressive symptoms in type 2 diabetes. J Affect Disord 2012;143:1–4.CrossRefGoogle ScholarPubMed
5. World Health Organization. Depression Fact Sheet; 2012. Available at http://www.who.int/mediacentre/factsheets/fs369/en/. Accessed March 10, 2014.Google Scholar
6. Ferrari, AJ, Charlson, FJ, Norman, RE et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med 2013;10:e1001547.Google Scholar
7. Reddy, MS. Depression: the disorder and the burden. Indian J Psychol Med 2010;32:1–2.Google Scholar
8. Murray, CJ, Vos, T, Lozano, R et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2197–2223.Google Scholar
9. Patki, G, Solanki, N, Atrooz, F, Allam, F, Salim, S. Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res 2013;1539:73–86.Google Scholar
10. Zatalia, SR, Sanusi, H. The role of antioxidants in the pathophysiology, complications, and management of diabetes mellitus. Acta Med Indones 2013;45:141–147.Google Scholar
11. Siwek, M, Sowa-Kucma, M, Dudek, D et al. Oxidative stress markers in affective disorders. Pharmacol Rep 2013;65:1558–1571.Google Scholar
12. Khansari, N, Shakiba, Y, Mahmoudi, M. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. IAD 2009;3:73–80.CrossRefGoogle Scholar
13. Leonard, B, Maes, M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 2012;36:764–785.Google Scholar
14. Aschbacher, K, O’Donovan, A, Wolkowitz, OM, Dhabhar, FS, Su, Y, Epel, E. Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity. Psychoneuroendocrinology 2013;38:1698–1708.Google Scholar
15. Terlecky, SR, Terlecky, LJ, Giordano, CR. Peroxisomes, oxidative stress, and inflammation. World J Biol Chem 2012;3:93–97.Google ScholarPubMed
16. Spiers, JG, Chen, HC, Sernia, C, Lavidis, NA. Activation of the hypothalamic–pituitary–adrenal stress axis induces cellular oxidative stress. Front Neurosci 2014;8:456.Google ScholarPubMed
17. Cavanagh, J, Mathias, C. Inflammation and its relevance to psychiatry. Adv Psychiatr Treat 2008;14:248–255.Google Scholar
18. Rustad, JK, Musselman, DL, Nemeroff, CB. The relationship of depression and diabetes: pathophysiological and treatment implications. Psychoneuroendocrinology 2011;36:1276–1286.Google Scholar
19. Katon, W. Depression and diabetes: unhealthy bedfellows. Depress Anxiety 2010;27:323–326.Google Scholar
20. Müller, N. Immunology of major depression. Neuroimmunomodulation 2014;21:123–130.Google Scholar
21. Anderson, RJ, Freedland, KE, Clouse, RE, Lustman, PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001;24:1069–1078.Google ScholarPubMed
22. Kumar, S, Pandey, AK. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal 2013;2013:1–16.Google Scholar
23. Liu, F, Agrawal, SG, Movasaghi, Z et al. Dietary flavonoids inhibit the anticancer effects of the proteasome inhibitor bortezomib. Blood 2008;112:3835–3846.Google Scholar
24. Kinoshita, T, Lepp, Z, Kawai, Y, Terao, J, Chuman, H. An integrated database of flavonoids. Biofactors 2006;26:179–188.CrossRefGoogle ScholarPubMed
25. Knekt, P, Kumpulainen, J, Jarvinen, R et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 2002;76:560–568.Google Scholar
26. Morand, C, Crespy, V, Manach, C, Besson, C, Demigne, C, Remesy, C. Plasma metabolites of quercetin and their antioxidant properties. Am J Physiol 1998;275:R212–R219.Google ScholarPubMed
27. Kahraman, A, Çakar, H, Köken, T. The protective effect of quercetin on long-term alcohol consumption-induced oxidative stress. Mol Biol Rep 2012;39:2789–2794.Google Scholar
28. Boots, AW, Haenen, GR, Bast, A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 2008;585:325–337.CrossRefGoogle ScholarPubMed
29. Kobori, M, Masumoto, S, Akimoto, Y, Takahashi, Y. Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice. Mol Nutr Food Res 2009;53:859–868.Google Scholar
30. Coskun, O, Kanter, M, Korkmaz, A, Oter, S. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas. Pharmacol Res 2005;51:117–123.CrossRefGoogle ScholarPubMed
31. Jeong, S, Kang, M, Choi, H, Kim, J, Kim, J. Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice. Nutr Res Pract 2012;6:201–207.Google Scholar
32. Kim, J, Kang, M, Choi, H, Jeong, S, Lee, Y, Kim, J. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutr Res Pract 2011;5:107–111.Google Scholar
33. Mohammadi, HS, Goudarzi, I, Lashkarbolouki, T, Abrari, K, Elahdadi Salmani, M. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats. Behav Brain Res 2014;270:196–205.CrossRefGoogle ScholarPubMed
34. Kawabata, K, Kawai, Y, Terao, J. Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats. J Nutr Biochem 2010;21:374–380.Google Scholar
35. Haleagrahara, N, Radhakrishnan, A, Lee, N, Kumar, P. Flavonoid quercetin protects against swimming stress-induced changes in oxidative biomarkers in the hypothalamus of rats. Eur J Pharmacol 2009;621:46–52.Google Scholar
36. Sabaté, E. Adherence to Long-Term Therapies: Evidence for Action. Geneva: World Health Organization, 2003.Google Scholar
37. Tamburrino, MB, Nagel, RW, Chahal, MK, Lynch, DJ. Antidepressant medication adherence. Prim Care Companion J Clin Psychiatry 2009;11:205–211.Google Scholar
38. Bogdanova, OV, Kanekar, S, D’Anci, KE, Renshaw, PF. Factors influencing behavior in the forced swim test. Physiol Behav 2013;118:227–239.Google Scholar
39. Caletti, G, Olguins, DB, Pedrollo, EF, Barros, HM, Helena, MT, Gomez, R. Antidepressant effect of taurine in diabetic rats. Amino Acids 2012;43:1525–1533.Google Scholar
40. Yankelevitch-Yahav, R, Franko, M, Huly, A, Doron, R. The forced swim test as a model of depressive-like behavior. J Vis Exp 2015;2.Google Scholar
41. McLaughlin, JP, Land, BB, Li, S, Pintar, JE, Chavkin, C. Prior activation of kappa opioid receptors by U50,488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning. Neuropsychopharmacology 2006;31:787–794.Google Scholar
42. Maciel, RM, Costa, MM, Martins, DB et al. Antioxidant and anti-inflammatory effects of quercetin in functional and morphological alterations in streptozotocin-induced diabetic rats. Res Vet Sci 2013;95:389–397.Google Scholar
43. Mahmoud, MF, Hassan, NA, El Bassossy, HM, Fahmy, A. Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PLoS One 2013;8:e63784.Google Scholar
44. Elbe, H, Vardi, N, Esrefoglu, M, Ates, B, Yologlu, S, Taskapan, C. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Hum Exp Toxicol 2014;34:100–113.Google ScholarPubMed
45. Oršolić, N, Gajski, G, Garaj-Vrhovac, V, Dikić, D, Prskalo, ZŠ, Sirovina, D. DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice. Eur J Pharmacol 2011;656:110–118.Google ScholarPubMed
46. Mahesh, T, Menon, VP. Quercetin allievates oxidative stress in streptozotocin-induced diabetic rats. Phytother Res 2004;18:123–127.Google Scholar
47. Chougala, MB, Bhaskar, JJ, Rajan, MGR, Salimath, PV. Effect of curcumin and quercetin on lysosomal enzyme activities in streptozotocin-induced diabetic rats. Clin Nutr 2012;31:749–755.Google Scholar
48. Zsila, F, Bikadi, Z, Simonyi, M. Probing the binding of the flavonoid, quercetin to human serum albumin by circular dichroism, electronic absorption spectroscopy and molecular modelling methods. Biochem Pharmacol 2003;65:447–456.Google Scholar
49. Silberberg, M, Morand, C, Manach, C, Scalbert, A, Remesy, C. Co-administration of quercetin and catechin in rats alters their absorption but not their metabolism. Life Sci 2005;77:3156–3167.Google Scholar
50. Lan, K, He, J, Tian, Y, Tan, F, Jiang, X, Wang, L et al. Intra-herb pharmacokinetics interaction between quercetin and isorhamentin. Acta Pharmacol Sin 2008;29:1376–1382.Google Scholar
51. Kim, HG, Lee, JH, Lee, SJ et al. The increased cellular uptake and biliary excretion of curcumin by quercetin: a possible role of albumin binding interaction. Drug Metab Dispos 2012;40:1452–1455.Google Scholar
52. Wang, Y, Zhao, Y, Yang, F, Yuan, Y, Wang, H, Xiao, J. Influences of glucose on the dietary hydroxyflavonoid-plasma protein interaction. J Agric Food Chem 2012;60:12116–12121.Google Scholar
53. Cryan, JF, Markou, A, Lucki, I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 2002;23:238–245.Google Scholar
54. Castagné, V, Porsolt, RD, Moser, P. Use of latency to immobility improves detection of antidepressant-like activity in the behavioral despair test in the mouse. Eur J Pharmacol 2009;616:128–133.Google Scholar
55. Merzoug, S, Toumi, ML, Tahraoui, A. Quercetin mitigates adriamycin-induced anxiety- and depression-like behaviors, immune dysfunction, and brain oxidative stress in rats. Naunyn Schmiedebergs Arch Pharmacol 2014;387:921–933.Google Scholar
56. Bhutada, P, Mundhada, Y, Bansod, K et al. Reversal by quercetin of corticotrophin releasing factor induced anxiety- and depression-like effect in mice. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:955–960.Google Scholar
57. Anjaneyulu, M, Chopra, K, Kaur, I. Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice. J Med Food 2003;6:391–395.Google Scholar
58. Chan, O, Inouye, K, Riddell, MC, Vranic, M, Matthews, SG. Diabetes and the hypothalamo-pituitary-adrenal (HPA) axis. Minerva Endocrinol 2003;28:87–102.Google Scholar
59. Maric, NP, Adzic, M. Pharmacological modulation of HPA axis in depression – new avenues for potential therapeutic benefits. Psychiatr Danub 2013;25:299–305.Google Scholar
60. Leiherer, A, Mündlein, A, Drexel, H. Phytochemicals and their impact on adipose tissue inflammation and diabetes. Vascul Pharmacol 2013;58:3–20.Google Scholar
61. Demir, EA, Oz, M, Alp, MI, Gergerlioglu, HS. Levels of IL-6 and TNF-a in diabetic rats: effect of quercetin. ISJMS 2015;1:27–31.Google Scholar
62. Gergerlioglu, HS, Gokbel, H, Okudan, N, Gergerlioglu, N, Demir, EA. Quercetin and caffeic acid phenethyl ester (CAPE) attenuate acute exercise-induced oxidative stress. Prog Nutr 2015;17:41–49.Google Scholar