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Current Psychiatry Research and Reviews

Editor-in-Chief

ISSN (Print): 2666-0822
ISSN (Online): 2666-0830

Research Article

Depression-reminiscent Behavior Induced by Chronic Unpredictable Mild Stress Paradigm in Mice Substantially Abrogated by Diosmin

Author(s): Abhishek Sharma*, Dinesh Dhingra, Rubina Bhutani, Amit Nayak and Adish Garg

Volume 20, Issue 3, 2024

Published on: 11 January, 2024

Page: [251 - 269] Pages: 19

DOI: 10.2174/0126660822261988231127072951

Price: $65

Abstract

Background: Diosmin has already been described and documented to be neuroprotective, antioxidant and anti-inflammatory. It may possess or hold depressionalleviating activity. Therefore, the purpose of the current research protocol is to investigate the depression-relieving proficiency of diosmin in stressed and unstressed mice.

Methods: Male mice (Swiss albino) were imperiled to an unpredictable chronic stress paradigm every day for three sequential weeks, and depression-resembling behavioral despair was induced. Imipramine 15 mg/kg and diosmin (25, 50 and 100 mg/kg) were dispensed for 21 successive days to discrete groups of stressed and unstressed mice.

Results: Both diosmin (100 mg/kg) and 15 mg/kg imipramine administration for 3 consecutive weeks substantially or significantly diminished the immobility period of mice imperiled to stress in comparison to stressed mice gauzed with the vehicle. Diosmin (25, 50 and 100 mg/kg) and imipramine considerably reinstated the diminished sucrose proclivity (sucrose preference percentage; %) in stressed mice, demonstrating their considerable or substantial depression-relieving effects. The locomotor activities of mice were not considerably altered by these drugs. Antidepressant-like activity of diosmin for immobility periods and preference for sucrose was observed to be analogous to imipramine. Diosmin (100 mg/kg) and imipramine substantially quashed CUMS- persuaded escalation of plasma corticosterone and nitrite levels, malondialdehyde levels and MAO-A activity in the brain of stressed mice. Both drugs also substantially reversed CUMS-prompted reduction in catalase activity and brain glutathione levels.

Conclusion: Accordingly, diosmin revealed significant anti-depressive activity in mice imperiled to chronic mild unpredictable stress paradigm conceivably via mitigation of nitrosative and oxidative stress, reticence of brain MAO-A action, and sink drop of plasma corticosterone degrees.

Graphical Abstract

[1]
Depressive disorder (depression). 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/depression
[2]
Diagnostic and Statistical Manual of Mental Disorders. (4th ed.), Washington, DC: American Psychiatric Association 1994.
[http://dx.doi.org/10.1017/S0033291700035765]
[3]
Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001; 7(5): 541-7.
[http://dx.doi.org/10.1038/87865] [PMID: 11329053]
[4]
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(2): 764-85.
[http://dx.doi.org/10.1016/j.neubiorev.2011.12.005] [PMID: 22197082]
[5]
Heuser I, Bissette G, Dettling M, et al. Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: Response to amitriptyline treatment. Depress Anxiety 1998; 8(2): 71-9.
[http://dx.doi.org/10.1002/(SICI)1520-6394(1998)8:2<71:AID-DA5>3.0.CO;2-N] [PMID: 9784981]
[6]
Delgado P, Moreno F. Antidepressants and the brain. Int Clin Psychopharmacol 1999; 14: S9-S16.
[http://dx.doi.org/10.1097/00004850-199905001-00003] [PMID: 10468323]
[7]
Tanabe A, Nomura S. Pathophysiology of depression. Nihon Rinsho 2007; 65(9): 1585-90.
[8]
Madrigal JLM, Moro MA, Lizasoain I, et al. Inducible nitric oxide synthase expression in brain cortex after acute restraint stress is regulated by nuclear factor κB-mediated mechanisms. J Neurochem 2001; 76(2): 532-8.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00108.x] [PMID: 11208916]
[9]
Maes M, De Vos N, Pioli R, et al. Lower serum vitamin E concentrations in major depression. J Affect Disord 2000; 58(3): 241-6.
[http://dx.doi.org/10.1016/S0165-0327(99)00121-4] [PMID: 10802134]
[10]
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis/chronic fatigue syndrome: Another pathway that may be associated with coronary artery disease and neuroprogression in depression. Neuroendocrinol Lett 2011; 32(2): 133-40.
[PMID: 21552194]
[11]
Pinto VL, Brunini T, Ferraz M, Okinga A, Mendes-Ribeiro A. Depression and cardiovascular disease: Role of nitric oxide. Cardiovasc Hematol Agents Med Chem 2008; 6(2): 142-9.
[http://dx.doi.org/10.2174/187152508783955060] [PMID: 18473779]
[12]
Dhingra D, Bansal S. Antidepressant-like activity of plumbagin in unstressed and stressed mice. Pharmacol Rep 2015; 67(5): 1024-32.
[http://dx.doi.org/10.1016/j.pharep.2015.03.001]
[13]
Sanacora G, Berman RM, Cappiello A, et al. Addition of the alpha2-antagonist yohimbine to fluoxetine: Effects on rate of antidepressant response. Neuropsychopharmacology 2004; 29(6): 1166-71.
[http://dx.doi.org/10.1038/sj.npp.1300418] [PMID: 15010697]
[14]
Sousa N, Cerqueira JJ, Almeida OFX. Corticosteroid receptors and neuroplasticity. Brain Res Brain Res Rev 2008; 57(2): 561-70.
[http://dx.doi.org/10.1016/j.brainresrev.2007.06.007] [PMID: 17692926]
[15]
Goldman LS, Nielsen NH, Champion HC. Awareness, diagnosis, and treatment of depression. J Gen Intern Med 1999; 14(9): 569-80.
[http://dx.doi.org/10.1046/j.1525-1497.1999.03478.x] [PMID: 10491249]
[16]
Millan MJ. The role of monoamines in the actions of established and “novel” antidepressant agents: A critical review. Eur J Pharmacol 2004; 500(1-3): 371-84.
[http://dx.doi.org/10.1016/j.ejphar.2004.07.038] [PMID: 15464046]
[17]
Anthony JT, Bertram GK, Susan BM. Pharmacology Examination and Board Review. (9th ed.), Singapore: McGraw-Hill Medical 2012.
[18]
Al-harbi KS. Treatment-resistant depression: Therapeutic trends, challenges, and future directions. Patient Prefer Adherence 2012; 6: 369-88.
[http://dx.doi.org/10.2147/PPA.S29716] [PMID: 22654508]
[19]
Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman’s pharmacological basis of therapeutics. (12th ed.), McGraw-Hill Medical 2011.
[20]
Singer A, Wonnemann M, Müller WE. Hyperforin, a major antidepressant constituent of St. John’s Wort, inhibits serotonin uptake by elevating free intracellular Na+1. J Pharmacol Exp Ther 1999; 290(3): 1363-8.
[PMID: 10454515]
[21]
Anjaneyulu M, Chopra K, Kaur I. Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice. J Med Food 2003; 6(4): 391-5.
[http://dx.doi.org/10.1089/109662003772519976] [PMID: 14977450]
[22]
Park SH, Sim YB, Han PL, Lee JK, Suh HW. Antidepressant-like Effect of Kaempferol and Quercitirin, Isolated from Opuntia ficus-indica var. saboten. Exp Neurobiol 2010; 19(1): 30-8.
[http://dx.doi.org/10.5607/en.2010.19.1.30] [PMID: 22110339]
[23]
Park SH, Sim YB, Han PL, Lee JK, Suh HW. Antidepressant-like effect of chlorogenic acid isolated from Artemisia capillaris Thunb. Anim Cells Syst 2010; 14(4): 253-9. b.
[http://dx.doi.org/10.1080/19768354.2010.528192]
[24]
Chhillar R, Dhingra D. Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress. Fundam Clin Pharmacol 2013; 27(4): 409-18.
[http://dx.doi.org/10.1111/j.1472-8206.2012.01040.x] [PMID: 22458864]
[25]
Dhingra D, Bhankher A. Behavioral and biochemical evidences for antidepressant-like activity of palmatine in mice subjected to chronic unpredictable mild stress. Pharmacol Rep 2014; 66(1): 1-9.
[http://dx.doi.org/10.1016/j.pharep.2013.06.001] [PMID: 24905299]
[26]
Dhingra D, Bansal Y. Antidepressant-like activity of beta-carotene in unstressed and chronic unpredictable mild stressed mice. J Funct Foods 2014; 7: 425-34.
[http://dx.doi.org/10.1016/j.jff.2014.01.015]
[27]
Cassani J, Dorantes-Barrón A, Novales L, Real G, Estrada-Reyes R. Anti-depressant-like effect of kaempferitrin isolated from Justicia spicigera Schltdl (Acanthaceae) in two behavior models in mice: evidence for the involvement of the serotonergic system. Molecules 2014; 19(12): 21442-61.
[http://dx.doi.org/10.3390/molecules191221442] [PMID: 25532842]
[28]
Amin B, Nakhsaz A, Hosseinzadeh H. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice. Avicenna J Phytomed 2015; 5(5): 458-68.
[PMID: 26468466]
[29]
Li R, Wang X, Qin T, Qu R, Ma S. Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain. Behav Brain Res 2016; 296: 318-25.
[http://dx.doi.org/10.1016/j.bbr.2015.09.031] [PMID: 26416673]
[30]
Wu S, Gao Q, Zhao P, et al. Sulforaphane produces antidepressant- and anxiolytic-like effects in adult mice. Behav Brain Res 2016; 301: 55-62.
[http://dx.doi.org/10.1016/j.bbr.2015.12.030] [PMID: 26721468]
[31]
Sharma A, Dhingra D, Dutt R. Syringic acid reversed depression-resembling behavior induced by chronic unpredictable mild stress paradigm in mice. Int J Pharm Sci Drug Res 2020; 13(6): 651-60.
[http://dx.doi.org/10.25004/IJPSDR.2021.130608]
[32]
Dholakiya SL, Benzeroual KE. Protective effect of diosmin on LPS-induced apoptosis in PC12 cells and inhibition of TNF-α expression. Toxicol In Vitro 2011; 25(5): 1039-44.
[http://dx.doi.org/10.1016/j.tiv.2011.04.003] [PMID: 21477647]
[33]
del Baño MJ, Lorente J, Castillo J, et al. Flavonoid distribution during the development of leaves, flowers, stems, and roots of Rosmarinus officinalis. postulation of a biosynthetic pathway. J Agric Food Chem 2004; 52(16): 4987-92.
[http://dx.doi.org/10.1021/jf040078p] [PMID: 15291464]
[34]
Senthamizhselvan O, Manivannan J, Silambarasan T, Raja B. Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion. Eur J Pharmacol 2014; 736: 131-7.
[http://dx.doi.org/10.1016/j.ejphar.2014.04.026] [PMID: 24769512]
[35]
Liu X, Zhang X, Zhang J, et al. Diosmin protects against cerebral ischemia/reperfusion injury through activating JAK2/STAT3 signal pathway in mice. Neuroscience 2014; 268: 318-27.
[http://dx.doi.org/10.1016/j.neuroscience.2014.03.032] [PMID: 24680937]
[36]
Queenthy SS, John B. Diosmin exhibits anti-hyperlipidemic effects in isoproterenol induced myocardial infarcted rats. Eur J Pharmacol 2013; 718(1-3): 213-8.
[http://dx.doi.org/10.1016/j.ejphar.2013.08.031] [PMID: 24036254]
[37]
Silambarasan T, Raja B. Diosmin, a bioflavonoid reverses alterations in blood pressure, nitric oxide, lipid peroxides and antioxidant status in DOCA-salt induced hypertensive rats. Eur J Pharmacol 2012; 679(1-3): 81-9.
[http://dx.doi.org/10.1016/j.ejphar.2011.12.040] [PMID: 22266490]
[38]
Tahir M, Rehman MU, Lateef A, et al. Diosmin abrogates chemically induced hepatocarcinogenesis via alleviation of oxidative stress, hyperproliferative and inflammatory markers in murine model. Toxicol Lett 2013; 220(3): 205-18.
[http://dx.doi.org/10.1016/j.toxlet.2013.04.004] [PMID: 23665045]
[39]
Li W, Li QJ, An SC. Preventive effect of estrogen on depression-like behavior induced by chronic restraint stress. Neurosci Bull 2010; 26(2): 140-6.
[http://dx.doi.org/10.1007/s12264-010-0609-9] [PMID: 20332819]
[40]
Pari L, Srinivasan S. Antihyperglycemic effect of diosmin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-nicotinamide-induced diabetic rats. Biomed Pharmacother 2010; 64(7): 477-81.
[http://dx.doi.org/10.1016/j.biopha.2010.02.001] [PMID: 20362409]
[41]
Mao QQ, Ip SP, Ko KM, Tsai SH, Che CT. Peony glycosides produce antidepressant-like action in mice exposed to chronic unpredictable mild stress: Effects on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33(7): 1211-6.
[http://dx.doi.org/10.1016/j.pnpbp.2009.07.002] [PMID: 19596036]
[42]
Kumar B, Kuhad A, Chopra K. Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: Behavioral and biochemical evidences. Psychopharmacology 2011; 214(4): 819-28.
[http://dx.doi.org/10.1007/s00213-010-2094-2] [PMID: 21103863]
[43]
Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology (Berl) 1985; 85(3): 367-70.
[http://dx.doi.org/10.1007/BF00428203] [PMID: 3923523]
[44]
Willner P, Towell A, Sampson D, Sophokleous S, Muscat R. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 1987; 93(3): 358-64.
[http://dx.doi.org/10.1007/BF00187257] [PMID: 3124165]
[45]
Bartos J, Pesez M. Colorimetric and Fluorimetric Analysis of Steroids. London: Academic Press 1976. Print
[46]
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982; 126(1): 131-8.
[http://dx.doi.org/10.1016/0003-2697(82)90118-X] [PMID: 7181105]
[47]
Schurr A, Livne A. Differential inhibition of mitochondrial monoamine oxidase from brain by hashish components. Biochem Pharmacol 1976; 25(10): 1201-3.
[http://dx.doi.org/10.1016/0006-2952(76)90369-5] [PMID: 938542]
[48]
Charles M, McEwan J. MAO activity in rabbit serum. In: Tabor H, Tabor CW, Eds. Methods in enzymology, vol XVIIB. New York, London: Academic Press 1977; pp. 692-8.
[49]
Henry RJDC, Winkelman JW. Clinical chemistry principles and techniques. Harper and Row 1974; Vol. 2: pp. 96-8.
[50]
Wills ED. Mechanisms of lipid peroxide formation in tissues Role of metals and haematin proteins in the catalysis of the oxidation of unsaturated fatty acids. Biochim Biophys Acta Lipids Lipid Metab 1965; 98(2): 238-51.
[http://dx.doi.org/10.1016/0005-2760(65)90118-9] [PMID: 14325327]
[51]
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82(1): 70-7.
[http://dx.doi.org/10.1016/0003-9861(59)90090-6] [PMID: 13650640]
[52]
Dhingra D, Gahalain N. Protective effect of ellagic acid against reserpine-induced orofacial dyskinesia and oxidative stress in rats. Pharmacologia 2016; 7(1): 16-21.
[http://dx.doi.org/10.5567/pharmacologia.2016.16.21]
[53]
Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.
[http://dx.doi.org/10.1016/S0076-6879(84)05016-3] [PMID: 6727660]
[54]
Willner P. Animal models as simulations of depression. Trends Pharmacol Sci 1991; 12(4): 131-6.
[http://dx.doi.org/10.1016/0165-6147(91)90529-2] [PMID: 2063478]
[55]
Willner P. Validity, reliability and utility of the chronic mild stress model of depression: A 10-year review and evaluation. Psychopharmacology 1997; 134(4): 319-29.
[http://dx.doi.org/10.1007/s002130050456] [PMID: 9452163]
[56]
Pariante CM, Lightman SL. The HPA axis in major depression: Classical theories and new developments. Trends Neurosci 2008; 31(9): 464-8.
[http://dx.doi.org/10.1016/j.tins.2008.06.006] [PMID: 18675469]
[57]
Nemeroff CB, Widerlöv E, Bissette G, et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984; 226(4680): 1342-4.
[http://dx.doi.org/10.1126/science.6334362] [PMID: 6334362]
[58]
Mason BL, Pariante CM. The effects of antidepressants on the hypothalamic-pituitary-adrenal axis. Drug News Perspect 2006; 19(10): 603-8.
[http://dx.doi.org/10.1358/dnp.2006.19.10.1068007] [PMID: 17299602]
[59]
Pan Y, Zhang WY, Xia X, Kong LD. Effects of icariin on hypothalamic-pituitary-adrenal axis action and cytokine levels in stressed Sprague-Dawley rats. Biol Pharm Bull 2006; 29(12): 2399-403.
[http://dx.doi.org/10.1248/bpb.29.2399] [PMID: 17142971]
[60]
Gao S, Cui YL, Yu CQ, Wang QS, Zhang Y. Tetrandrine exerts antidepressant-like effects in animal models: Role of brain-derived neurotrophic factor. Behav Brain Res 2013; 238: 79-85.
[http://dx.doi.org/10.1016/j.bbr.2012.10.015] [PMID: 23085478]
[61]
Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35(3): 676-92.
[http://dx.doi.org/10.1016/j.pnpbp.2010.05.004] [PMID: 20471444]
[62]
Dhingra D, Valecha R. Punarnavine, an alkaloid isolated from ethanolic extract of Boerhaavia diffusa Linn. reverses depression-like behaviour in mice subjected to chronic unpredictable mild stress. Indian J Exp Biol 2014; 52(8): 799-807.
[PMID: 25141543]
[63]
Bilici M, Efe H, Köroğlu MA, Uydu HA, Bekaroğlu M, Değer O. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 2001; 64(1): 43-51.
[http://dx.doi.org/10.1016/S0165-0327(00)00199-3] [PMID: 11292519]
[64]
Réus GZ, Stringari RB, de Souza B, et al. Harmine and imipramine promote antioxidant activities in prefrontal cortex and hippocampus. Oxid Med Cell Longev 2010; 3(5): 325-31.
[http://dx.doi.org/10.4161/oxim.3.5.13109] [PMID: 21150338]
[65]
Pendyala V, Thakur SR, Yadikar L, Chinta MD. Chrysin attenuates chronic unpredictable mild stress induced changes in behavior, inflammation and improves adrenergic, serotonergic function: An in vivo and biochemical study. Toxicol Int 2022; 29(3): 393-403.
[http://dx.doi.org/10.18311/ti/2022/v29i3/29153]
[66]
Shabani S, Mirshekar MA. Diosmin is neuroprotective in a rat model of scopolamine-induced cognitive impairment. Biomed Pharmacother 2018; 108: 1376-83.
[http://dx.doi.org/10.1016/j.biopha.2018.09.127] [PMID: 30372840]
[67]
Mirshekar MA, Fanaei H, Keikhaei F, Javan FS. Diosmin improved cognitive deficit and amplified brain electrical activity in the rat model of traumatic brain injury. Biomed Pharmacother 2017; 93: 1220-9.
[http://dx.doi.org/10.1016/j.biopha.2017.07.014] [PMID: 28738538]
[68]
Estrada-Camarena E, Fernández-Guasti A, López-Rubalcava C. Antidepressant-like effect of different estrogenic compounds in the forced swimming test. Neuropsychopharmacology 2003; 28(5): 830-8.
[http://dx.doi.org/10.1038/sj.npp.1300097] [PMID: 12637949]
[69]
Antoniuk S, Bijata M, Ponimaskin E, Wlodarczyk J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci Biobehav Rev 2019; 99: 101-16.
[http://dx.doi.org/10.1016/j.neubiorev.2018.12.002] [PMID: 30529362]
[70]
Vafa A, Afzal SM, Barnwal P, et al. Protective role of diosmin against testosterone propionate-induced prostatic hyperplasia in Wistar rats: Plausible role of oxidative stress and inflammation. Hum Exp Toxicol 2020; 39(9): 1133-46.
[http://dx.doi.org/10.1177/0960327119889655] [PMID: 31797688]
[71]
Wójciak M, Feldo M, Borowski G, Kubrak T, Płachno BJ, Sowa I. Antioxidant potential of diosmin and diosmetin against oxidative stress in endothelial cells. Molecules 2022; 27(23): 8232.
[http://dx.doi.org/10.3390/molecules27238232] [PMID: 36500323]
[72]
Huang M, Singh N, Kainth R, Khalid M, Kushwah AS, Kumar M. Mechanistic insight into diosmin-induced neuroprotection and memory improvement in intracerebroventricular-quinolinic acid rat model: Resurrection of mitochondrial functions and antioxidants. Evid Based Complement Alternat Med 2022; 2022: 1-14.
[http://dx.doi.org/10.1155/2022/8584558] [PMID: 35300069]
[73]
Okubo EAE, Ben-Azu B, Mayowa AA, Oladele AA. Diosmin attenuates schizophrenia-like behavior, oxidative stress, and acetylcholinesterase activity in mice. Drug Metabol Drug Interact 2020; 35(4): 20200119.
[http://dx.doi.org/10.1515/dmpt-2020-0119] [PMID: 34704698]
[74]
Li T, Zhu W, Liu G, Fang C, Quan S. Diosmin for the prevention of ovarian hyperstimulation syndrome. Int J Gynaecol Obstet 2020; 149(2): 166-70.
[http://dx.doi.org/10.1002/ijgo.13100] [PMID: 31925779]
[75]
Eraslan G, Sarıca ZS, Bayram LÇ, Tekeli MY, Kanbur M, Karabacak M. The effects of diosmin on aflatoxin-induced liver and kidney damage. Environ Sci Pollut Res Int 2017; 24(36): 27931-41.
[http://dx.doi.org/10.1007/s11356-017-0232-7] [PMID: 28988357]

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