The effect of hesperetin on depression and anxiety induced by reserpine injection in male rats

Document Type : Research Paper

Authors

1 Physiology Medicine, Shahed University, Tehran, Iran

2 Department of Physiology, School of Medicine,Shahed University,Tehran , Iran

3 Department of Physiology, Faculty of Medicine, Shahed University, Tehran, Iran

4 Department of Pharmacy, Faculty of Pharmacy, Jundishapur University, Ahvaz, Iran

Abstract

Background and Objective: Hesperetin is a citrus skin active ingredient with neuroprotective and antioxidant properties. In this study,we evaluted the therapeutic effect of hesperetin on depression and anxiety induced by reserpine injection according to behavioral tests in rats.
Materials and Methods: For this evaluation, 60 male rats weighing 230-250 mg / kg were divided into six groups, control group receiving saline for 14 days , groups receiving hesperetin (20 and 10 mg / kg for 7 days) , depressed group with reserpine (0.2 mg / kg for 14 days) and depressed groups receiving hesperetin (20 and 10 mg / kg for 7 days). After taking the drugs, the effect of hesperetin was evaluated in behavioral tests.on depression and anxiety.   
Results: The results showed that hesperetin significantly reduced the anxiety of depressed animals in Open Field and Elevated Plus Maze Tests (P <0.05). In Forced Swimming Test, hesperetin 20 mg / kg caused a significant decrease in immobility time (P <0.001), and also, hesperetin could decrease the immobility time in depressed groups(P <0.05).According to Sucrose Preference Test's data, rats that received 20 mg / kg of hesperetin were more prone to sweet water in compared with reserpine received group.
Conclusion: According to the results of this study, hesperetin is effective in reserpine-induced depressive symptoms in rats.

Keywords


  1. Saghafian F, Malmir H, Saneei P, Milajerdi A, Larijani B, Esmaillzadeh A. Fruit and vegetable consumption and risk of depression : accumulative evidence from an updated systematic review and meta-analysis of epidemiological studies. British Journal of Nutrition 2018; 119: 1087–1101.
  2. Zou L, Yeung A. Effects of Meditative Movements on Major Depressive Disorder : A       Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of Clinical Medicine 2018; 7(8):195.
  3. Mitchell ND, Baker GB. An update on the role of glutamate in the pathophysiology of depression. Acta Psychiatrica Scandinavica 2010; 122: 192–210.
  4. Chávez-Castillo M, Núñez V, Nava M, Ortega Á, Rojas M, Bermúdez V,et al. Depression as a Neuroendocrine Disorder : Emerging Neuropsychopharmacological Approaches beyond Monoamines. Advances in Pharmacological Sciences 2019; 3(2019):7943481.
  5. Duman RS. Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connectionst. Dialogues in Clinical Neuroscience 2014; 16(1):11-27.
  6. Ratajczak P, Kus K, Zaprutko T, Szczepański M, Rusowicz S, Nowakowska E. Antidepressant and anxiolytic efficacy of single, chronic and concomitant use of vortioxetine , dapoxetine and fluoxetine in prenatally stressed rats. Acta Neurobiologiae Experimentalis 2019; 79(1):13-24.
  7. Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R. Oxidative damage and major depression : the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Report 2003; 8(6):365-70.
  8. Lopresti AL, Maker GL, Hood SD, Drummond PD. A review of peripheral biomarkers in major depression : The potential of in fl ammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry 2014; 3(48):102-11.
  9. Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: From monoamines to glutamate. Experimental and Clinical Psychopharmacology 2015; 23(1):1-21.
  10. Friedman MA, Detweiler-Bedell JB, Leventhal HE, Horne R, Keitner GI, Miller IW. Combined Psychotherapy and Pharmacotherapy for the Treatment of Major Depressive Disorder. Clinical Psycholigy: Science and Practice 2004; 11: 47–68.
  11. Fajemiroye JO, da Silva DM, de Oliveira DR, Costa EA, Treatment of anxiety and depression : medicinal plants in retrospect. Fundamental and Clinical Pharmacology 2016; 30(3):198-215.
  12. Kheradmand E, Mahboobeh Z, Zare M. Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer’s disease. Biomedicine & Pharmacotherapy 2018; 97:1096-1101.
  13. Ishola IO, Jacinta AA, Adeyem OO. Cortico-hippocampal memory enhancing activity of hesperetin on scopolamine-induced amnesia in mice : role of antioxidant defense system, cholinergic neurotransmission and expression of BDNF. Metabolic Brain Disease 2019; 34(4):979-989.
  14. Antkiewicz-Michaluk L, Wasik A,  Mozdzen E,  Romanska I,  Michaluk J. Antidepressant-like Effect of Tetrahydroisoquinoline Amines in the Animal Model of Depressive Disorder Induced by Repeated Administration of a Low Dose of Reserpine : Behavioral and Neurochemical Studies in the Rat. Neurotoxicity Research 2014; 26(1):85-98.
  15.  Tanaka S, Young JW, Halberstadt AL, Masten VL, Geyer MA. Four factors underlying mouse behavior in an open field. Behavioural Brain Research 2012; 233(1):55-61.
  16.  Mohammadi M, Parsi B. Anxiety–related Behavioral Alterations Following Repeated Paraoxon Exposure in Rats. Journal of Mazandaran University of Medical Sciences 2014; 24(117): 116-124
  17. Walf1 AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols 2007; 2(2):322-8. 
  18. Luo J, Min S, Wei K, Cao J, Wang B, Li P, et al. Propofol prevents electroconvulsive-shock- induced memory impairment through regulation of hippocampal synaptic plasticity in a rat model of depression. Neuropsychiatric Disease and Treatment 2014; 23(10):1847-59.
  19. Donovan SO, Dalton V, Harkin A, Mcloughlin DM. Effects of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour in the corticosterone model of depression. International Journal of Neuropsychopharmacology 2014; 17(9):1477-86.
  20. Ikram M, Muhammad T, Ur Rehman S,  Khan A, Gi Jo M, Ali T, et al. Hesperetin Confers Neuroprotection by Regulating Nrf2/TLR4/NF-κB Signaling in an Aβ Mouse Model. Molecular Neurobiology 2019; 56(9):6293-6309.
  21. Zahedi E, Sanaie Rad A, Khalili M, Esmail Jamaat E, Salari S. The effect of electroconvulsive therapy on the levels of oxidative stress factors in the prefrontal cortex of depressed rats. Journal of Basic and Clinical Pathophysiology 2018;6(2):27-31
  22. Zhang F, Luo J, Min S, Ren L, Qin P. Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats. Brain Research 2016; 1(1642):43-50.
  23. Valvassori SS., Varela RB, Quevedo J. Animal Models of Mood Disorders: Focus on Bipolar Disorder and Depression. Book Chapter: Animal Models for the Study of Human Disease 2017; 991-1001.