A Natural Phenolic Compound Quercetin Showed the Usefulness by Targeting Inflammatory, Oxidative Stress Markers and Augment 5-HT Levels in One of the Animal Models of Depression in Mice

Khadeeja Khan; Abul Kalam Najmi; Mohd Akhtar

doi:10.1055/a-0748-5518

Drug Research, Table of Contents

Drug Res (Stuttg) 2019; 69(07): 392-400
DOI: 10.1055/a-0748-5518

Original Article

A Natural Phenolic Compound Quercetin Showed the Usefulness by Targeting Inflammatory, Oxidative Stress Markers and Augment 5-HT Levels in One of the Animal Models of Depression in Mice

Authors

Khadeeja Khan

¹Department of Pharmacology, School of Pharmaceutical Education and Research (Formerly: Faculty of Pharmacy), Jamia Hamdard, New Delhi, India
Abul Kalam Najmi

¹Department of Pharmacology, School of Pharmaceutical Education and Research (Formerly: Faculty of Pharmacy), Jamia Hamdard, New Delhi, India
Mohd Akhtar

¹Department of Pharmacology, School of Pharmaceutical Education and Research (Formerly: Faculty of Pharmacy), Jamia Hamdard, New Delhi, India

Abstract

Aim In the present study quercetin was studied for its role in inflammation, oxidative stress markers and 5-HT levels in unpredictable chronic mild stress (UCMS) animal model of depression.

Materials and Methods The mice were randomized into different groups trained for UCMS protocol followed by different drug treatments. Treatments were started after 2 weeks from the start of UCMS protocol and continued up to 6 weeks. The behavioral tests such as modified forced swimming (MFST), tail suspension (TST) and open field tests were performed on week 6, at least 24 h after the last drug treatment. Behavioral tests were preceded following animal sacrifice for biochemical estimations.

Results A significant decrease in swimming, climbing times and increase in immobility time in MFST and TST was observed in UCMS group. Administration of quercetin (25 mg/kg per orally (p.o) reversed these times in MFST and TST. A decrease in no. of field crossing, time spent in centre and no. of rearing were observed in UCMS group. Quercetin reduced these observations in open field test. There was a decrease in superoxide dismutase (SOD), glutathione (GSH), catalase and 5 HT levels in the brain tissue. Quercetin treatment significantly augmented SOD, GSH, catalase and 5 HT levels. Glutamate, TNF-α and IL-6 levels were increased in UCMS group while quercetin decreased these cytokines.

Conclusion Quercetin resulted antidepressant-like effect by its antioxidant, anti-inflammatory activities, reduced excitotoxicity and augmented 5 HT levels. This pointed out the usefulness of this phenolic compound as adjuvent drug along with other antidepressant drugs.

Key words

Depression - Phenolic compound quercetin - antioxidant - anti-inflammatory - 5-HT levels

Full Text

References

References
1 Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. 1996 Cambridge, MA Harvard University Press Most comprehensive study of comparative disease burdens ever undertaken. Major depression estimated to be among the most burdensome disorders worldwide 2008; 43: 619-626
2 Racagni G, Popoli M. The pharmacological properties of antidepressants. Int Clin Psychopharmacol 2010; 25: 117-131
3 Schildkraut JJ, Kety SS. Biogenic amines and emotion. Science 1967; 156: 21-37
4 Cryan F, Lucki I. Antidepressant like behavioral effect mediated by 5- Hydroxytryptamine _2C receptors. J Pharmacol Exp Ther 2000; 295: 1120-1126
5 Dantzer R, O’Connor JC, Freund GG. et al. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat Rev Neurosci 2008; 9: 45-46
6 Raison CL, Capuron L, Miller AH. Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends Immunol 2006; 27: 24-31
7 Kendler KS, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. American Journal Psychiatry 1999; 156: 837-841
8 Joels M, Karst H, Alfarez D. et al. Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 2004; 7: 221-231
9 Segerstrom SC, Miller GE. Psychological stress and the immune system: A meta-analytic study of 30 years of inquiry. Psychological Bulletin 2004; 130: 601-630
10 Kim MS, Kim MK, Kim KS. et al. Cytotoxicity of 1,2-diacetylbenzene in human neuroblastoma SHSY5Y cells is mediated by oxidative stress. Toxicology 2008; 243: 216-223
11 Maes M, Galecki P, Chang YS. et al. A review on the oxidative and nitrosative stress pathways in major depression and their possible contribution to the (neuro)-degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 676-692
12 Bishop A, Anderson JE. NO signaling in the CNS: From the physiological to the pathological. Toxicology 2005; 208: 193-205
13 Dovichi SS, Lajolo FM. Flavonoids and their relationship to diseases of the central nervous system. Nutr J Braz Soc Food Nutr 2011; 36: 123-135
14 Holzmann I, Mota da Silva M, Afonso Corrêa da Silva J. et al. Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways. Pharmacol Biochem Behavior 2015; 136: 55-63
15 Anjaneyulu M, Chopra K, Kaur I. Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice. J Med Food 2003; 4: 391-395
16 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
17 Korkina LG, Afanas’ev IB. Antioxidant and chelating properties of flavonoids. Adv Pharmacol 1997; 38: 151-163
18 Chang WS, Lee YJ, Lu FJ. et al. Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res 1993; 13: 2165-2170
19 Shoskes DA. Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: a new class of renoprotective agents. Transplantation 1998; 66: 147-152
20 Nelson CW, Wei EP, Povlishock JT. et al. Oxygen radicals in cerebral ischemia. Am J Physiol 1992; 263: H1356-H1362
21 Ferrali M, Signorini C, Caciotti B. et al. Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity. FEBS Lett 1997; 416: 123-129
22 Knekt P, Jarvinen R, Reunanen A. et al. Flavonoid intake and coronary mortality in Finland: A cohort study. BMJ 1996; 312: 478-481
23 Ferrandiz ML, Alcaraz MJ. Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents Actions 1991; 32: 283-288
24 Nabavi SM, Nabavi SF, Hebtemarium S. et al. Ameliorative Effects of Quercetin on Sodium Fluoride-Induced Oxidative Stress in Rat’s Kidney. Renal Failure 2012; 34: 901-906
25 Ansari M. Neha Khan HA. Quercetin alleviate oxidative stress and inflammation through upregulation of antioxidant machinery and down-regulation of COX2 and NF-κB expression in collagen induced rheumatoid arthritis. Int J Drug Del Res 2014; 6: 215-230
26 Nollet M, Galliard P, Minier F. et al. Activation of orexin neurons in dorsomedial/ perifornical hypothalamus and antidepressant reversal in a rodent model of depression. Neuropharmacology 2011; 61: 336-346
27 Cryan JF, Page ME, Lucki I. Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test. Eur J Pharmacol 2002; 436: 197-205
28 Ripoll N, Denis J, Paul D. et al. Antidepressant-like effects in various mice strains in the tail suspension test. J Neu Bio Rev 2003; 143: 193-200
29 Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviours: A review. Eur J Pharmacol 2003; 463: 3-33
30 Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974; 47: 469-474
31 Ellman GL. Tissue sulfhydryl group. Arch Biochem Biophys 1959; 82: 70-77
32 Sedlak J, Lindsay RH. Estimation of Total Protein-Bound, and Nonprotein Sulfhydryl Groups in Tissue with Ellman’s Reagent. Analytical Biochemistry 1968; 25: 1192-1205
33 Claiborne A, Greenworld RA. Handbook of method of oxygen free radical research. Boca Rated FL: CRC Press; 1985. 84 283-284
34 Curzon G, Green AR. Rapid method for the determination of 5- hydroxyl tryptamine and 5-hydroxy indole acetic acid in small regions of rat brain. Life Sci Oxford 1968; 7: 653-655
35 Brent E, Bergmeyer HU. L-Glutamate UV-Assay with glutamate dehydrogenase and NAD Methods of enzymatic analysis, edited by Hans Ulrich Bergmeyer. 1965; 2: 1704-1708
36 Lowry OH, Rosenbrough NJ, Farr AL. et al. Protein measurement with Folin phenol reagent. J Bio Chem 1951; 193: 265-275
37 Pudell C, Vicente BA, Delattre AM. et al. Fish oil improves anxiety-like, depressive-like and cognitive behaviors in olfactory bulbectomized rats. Eu J Neurosci 2014; 39: 266-274
38 Xu C, Teng J, Chen W. et al. 20 (s)-protopanaxadol, an active ginseng metabolite, exhibits strong antidepressant-like effect in animal test. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1402-1411
39 Lee B, Shim I, Lee H. et al. Effect of genseoside Re on depression and anxiety-like behaviors and cognitive memory deficit induced by repeated immobilization in rats. J Microbiol Biotech 2012; 22: 708-720
40 Harkin A, Connor TJ, Walsh MST. et al. Serotonergic mediation of the antidepressant-like effects of nitric oxide synthase inhibitors. Neuropharmacology 2003; 44: 616-623
41 Hellweg R, Züger M, Fink K. et al. Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression related brain areas. Neurobiol Dis 2007; 25: 1-7
42 Romeas T, Morissette MC, Mnie-Filali O. et al. Simultaneous anhedonia and exaggerated locomotor activation in an animal model of depression. Psychopharmacology 2009; 205: 293-303
43 Zueger M, Urani A, Chourbaji S. et al. Olfactory bulbectomy in mice induces alterations in exploratory behavior. Neurosci Lett 2005; 374: 142-146
44 Machado DG, Cunha MP, Neis VB. et al. Fluoxetine reverses depressive - like behaviors and increases hippocampal acetylcholinesterase activity induced by olfactory bulbectomy. Pharmacol Biochem Behav 2012; 103: 220-229
45 Pochwat B, Sowa-Kucma M, Kotarska K. et al. Antidepressant-like activity of magnesium in the olfactory bulbectomy model is associated with AMPA/BDNF pathway. Psychopharmacology 2015; 232: 355-367
46 Kumar A, Goyal R. Quercetin protects against acute immobilization stress-induced behaviors and biochemical alterations in mice. J Med Food 2008; 11: 469-473
47 Haleagrahara N, Radhakrishnan A, Lee N. et al. Flavonoid quercetin protects against swimming stress-induced changes in oxidative biomarkers in the hypothalamus of rat. Eu J Pharmcol 2009; 621: 46-52
48 Rinwa P, Kumar A. Quercetin suppress microglial neuroinflammatory response and induce antidepressant-like effect in olfactory bulbectomized rats. Neuroscience 2013; 255: 86-98
49 Castren E, Volkar V, Rantamaki T. Role of neutrophic factor in depression. Curr Opin. Pharmacology 2007; 7: 18-21
50 Abdel-Wahaba BA, Salamab RH. Venlafexine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharm Biochem Behav 2011; 100: 59-65
51 Coskun O, Kanter M, Korkmaz A. et al. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacol Res 2005; 51: 117-123
52 Kook D, Wolf AH, Yu AL. et al. The protective effect of quercetin against oxidative stress in the human RPE in vitro. Invest Ophthalmol Vis Sci 2008; 49: 1712-1720
53 Romero M, Jiménez R, Sánchez M. et al. Quercetin inhibits vascular superoxide production induced by endothelin-1: Role of NADPH oxidase, uncoupled eNOS and PKC. Atherosclerosis 2009; 202: 58-67
54 Reichenberg A, Yirmiya R, Schuld A. et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 2001; 58: 445-452
55 Brydon L, Harrison NA, Walker C. et al. Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry 2008; 63: 1022-1029
56 Khanra R, Diwanjee S, Dua TK. et al. Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response. J Transl Med 2015; 13: 6. doi:10.1186/s12967-014-0364-1
57 Lee BH, Jeong SM, Lee JH. et al. Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pre-transmembrane domain I. Mol Cells 2005; 20: 69-73
58 Harmer CJ, Reid CB, Ray MK. et al. 5HT₃ antagonism abolishes the motion potentiated startle effect in humans. Psychopharmacology (Berl) 2006; 186: 18-24
59 Kao TK, Ou YC, Raung SL. et al. Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia. Life Sci 2010; 86: 315-321

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