Generic placeholder image

Current Pharmaceutical Design

Author(s): Shakiba Nasiri Boroujeni, Zahra Lorigooini, Fatemeh Rahimi Boldaji and Hossein Amini-Khoei*

DOI: 10.2174/1381612826666200717083211

DownloadDownload PDF Flyer Cite As
Diosgenin via NMDA Receptor Exerted Anxiolytic-like Effect on Maternally Separated Mice

Page: [440 - 445] Pages: 6

  • * (Excluding Mailing and Handling)

Abstract

Background and aim: Anxiety is one of the most common psychiatric disorders that lead to the disruption of daily life and also the quality of life. Routine medications have many side effects and cause physical dependence and psychosocial addiction. Diosgenin is a phytosteroid found in a number of herbs. The present study aimed to investigate the anxiolytic-like effect of diosgenin in the maternal separation model in male mice focusing on the role of NMDA receptors.

Materials and Methods: Maternal separation (MS) paradigm was performed daily (3 h) from postnatal day (PND) 2-14. Male mice were treated with different doses of diosgenin to find effective and sub-effective doses. In the next step, mice were treated with an effective dose of diosgenin plus NMDA and or a sub-effective dose of diosgenin plus ketamine (NMDA antagonist). Valid behavioral tests for the evaluation of anxiety-like behavior were performed. Then, mice were euthanized, the hippocampus was dissected out and gene expression of NMDA receptors (NR2a and NR2b subunits) was assessed.

Results: MS provokes anxiety-like behaviors in the open field test (OFT) and elevated plus maze (EPM) test. Diosgenin significantly mitigated the negative effects of MS. Co-administration of NMDA attenuated anxiolyticlike effect of the effective dose of diosgenin, while ketamine potentiated the anxiolytic effect of sub-effective dose of diosgenin. Furthermore, MS increased the expression of the NMDA receptor in the hippocampus which to some extent modulated with diosgenin.

Conclusion: Diosignin has an anxiolytic-like effect on MS mice which at least, in part, mediated through NMDA receptors.

Keywords: Maternal separation, anxiety, diosignin, NMDA receptor, mice.

[1]
Schicho R, Marsche G, Storr M. Cardiovascular complications in inflammatory bowel disease. Curr Drug Targets 2015; 16(3): 181-8.
[http://dx.doi.org/10.2174/1389450116666150202161500] [PMID: 25642719]
[2]
Jones-Bitton A, Best C, MacTavish J, Fleming S, Hoy S. Stress, anxiety, depression, and resilience in Canadian farmers. Soc Psychiatry Psychiatr Epidemiol 2020; 55(2): 229-36.
[http://dx.doi.org/10.1007/s00127-019-01738-2] [PMID: 31197397]
[3]
Nugent NR, Tyrka AR, Carpenter LL, Price LH. Gene-environment interactions: early life stress and risk for depressive and anxiety disorders. Psychopharmacology (Berl) 2011; 214(1): 175-96.
[http://dx.doi.org/10.1007/s00213-010-2151-x] [PMID: 21225419]
[4]
Juruena MF, et al. The role of early life stress in HPA axis and anxiety Anxiety Disorders. Springer 2020; pp. 141-53.
[http://dx.doi.org/10.1007/978-981-32-9705-0_9]
[5]
Henry LM, Steele EH, Watson KH, et al. Stress exposure and maternal depression as risk factors for symptoms of anxiety and depression in adolescents. Child Psychiatry Hum Dev 2019; 1-13.
[http://dx.doi.org/10.1007/s10578-019-00940-2] [PMID: 31729628]
[6]
Kino T. Stress, glucocorticoid hormones, and hippocampal neural progenitor cells: implications to mood disorders. Front Physiol 2015; 6: 230.
[http://dx.doi.org/10.3389/fphys.2015.00230] [PMID: 26347657]
[7]
Aisa B, Tordera R, Lasheras B, Del Río J, Ramírez MJ. Effects of maternal separation on hypothalamic-pituitary-adrenal responses, cognition and vulnerability to stress in adult female rats. Neuroscience 2008; 154(4): 1218-26.
[http://dx.doi.org/10.1016/j.neuroscience.2008.05.011] [PMID: 18554808]
[8]
Lippmann M, Bress A, Nemeroff CB, Plotsky PM, Monteggia LM. Long-term behavioural and molecular alterations associated with maternal separation in rats. Eur J Neurosci 2007; 25(10): 3091-8.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05522.x] [PMID: 17561822]
[9]
Sevi A, Caroprese M, Annicchiarico C, Albenzio M, Taibi L, Muscio A. The effect of a gradual separation from the mother on later behavioral, immune and endocrine alterations in artificially reared lambs. Appl Anim Behav Sci 2003; 83(1): 41-53.
[http://dx.doi.org/10.1016/S0168-1591(03)00088-1]
[10]
Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J Neurochem 1984; 42(1): 1-11.
[http://dx.doi.org/10.1111/j.1471-4159.1984.tb09689.x] [PMID: 6139418]
[11]
Barkus C, McHugh SB, Sprengel R, Seeburg PH, Rawlins JN, Bannerman DM. Hippocampal NMDA receptors and anxiety: at the interface between cognition and emotion. Eur J Pharmacol 2010; 626(1): 49-56.
[http://dx.doi.org/10.1016/j.ejphar.2009.10.014] [PMID: 19836379]
[12]
Javitt DC. Glutamate as a therapeutic target in psychiatric disorders. Mol Psychiatry 2004; 9(11): 984-97.
[http://dx.doi.org/10.1038/sj.mp.4001551] [PMID: 15278097]
[13]
Guimarães FS, Carobrez AP, De Aguiar JC, Graeff FG. Anxiolytic effect in the elevated plus-maze of the NMDA receptor antagonist AP7 microinjected into the dorsal periaqueductal grey. Psychopharmacology (Berl) 1991; 103(1): 91-4.
[http://dx.doi.org/10.1007/BF02244080] [PMID: 1672463]
[14]
Lal H, Shearman GT. Interoceptive discriminative stimuli in the development of CNS drugs and a case of an animal model of anxiety Annual Reports in Medicinal Chemistry. Elsevier 1980; pp. 51-8.
[http://dx.doi.org/10.1016/S0065-7743(08)60367-X]
[15]
Meyer JS, Quenzer LF. Psychopharmacology: Drugs, the brain, and behavior. Sinauer Associates 2005.
[16]
Sharafzadeh S, Alizadeh O. Some medicinal plants cultivated in Iran. J Appl Pharm Sci 2012; 2(1): 134-7.
[17]
Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol 2011; 21(12): 841-60.
[http://dx.doi.org/10.1016/j.euroneuro.2011.04.002] [PMID: 21601431]
[18]
Yang D-J, Lu T-J, Hwang LS. Isolation and identification of steroidal saponins in Taiwanese yam cultivar (Dioscorea pseudojaponica Yamamoto). J Agric Food Chem 2003; 51(22): 6438-44.
[http://dx.doi.org/10.1021/jf030390j] [PMID: 14558759]
[19]
Ho Y-J, Wang CF, Hsu WY, et al. Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level. Ann Gen Psychiatry 2007; 6(1): 21.
[http://dx.doi.org/10.1186/1744-859X-6-21] [PMID: 17688703]
[20]
Zhang X, Xue X, Zhao J, et al. Diosgenin attenuates the brain injury induced by transient focal cerebral ischemia-reperfusion in rats. Steroids 2016; 113: 103-12.
[http://dx.doi.org/10.1016/j.steroids.2016.07.006] [PMID: 27425638]
[21]
Rajadurai UM, Azhagiyamanavalan LP, Hariharan A, Antony J, et al. Anxiolytic and anti-depressant effects of AgNPs fabricated using diosgenin. SSRN Electronic J 2019.
[http://dx.doi.org/10.2139/ssrn.3370113]
[22]
Liu J, He X, Zhen P, et al. Sirtuin type 1 signaling pathway mediates the effect of diosgenin on chondrocyte metabolisms in osteoarthritis. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2017; 42(2): 121-7.
[23]
Gong G, Qin Y, Huang W. Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis C.H. Wright in vitro and in vivo. Phytomedicine 2011; 18(6): 458-63.
[http://dx.doi.org/10.1016/j.phymed.2010.08.015] [PMID: 21036572]
[24]
Pickering C, Gustafsson L, Cebere A, Nylander I, Liljequist S. Repeated maternal separation of male wistar rats alters glutamate receptor expression in the hippocampus but not the prefrontal cortex. Brain Res 2006; 1099(1): 101-8.
[http://dx.doi.org/10.1016/j.brainres.2006.04.136] [PMID: 16784730]
[25]
Roceri M, Hendriks W, Racagni G, Ellenbroek BA, Riva MA. Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus. Mol Psychiatry 2002; 7(6): 609-16.
[http://dx.doi.org/10.1038/sj.mp.4001036] [PMID: 12140784]
[26]
Lorigooini Z, Sadeghi Dehsahraei K, Bijad E, Habibian Dehkordi S, Amini-Khoei H. Trigonelline through the attenuation of oxidative stress exerts antidepressant-and anxiolytic-like effects in a mouse model of maternal separation stress. Pharmacology 2020; 105(5-6): 289-99.
[http://dx.doi.org/10.1159/000503728] [PMID: 31630147]
[27]
Nouri A, Hashemzadeh F, Soltani A, Saghaei E, Amini-Khoei H. Progesterone exerts antidepressant-like effect in a mouse model of maternal separation stress through mitigation of neuroinflammatory response and oxidative stress. Pharm Biol 2020; 58(1): 64-71.
[http://dx.doi.org/10.1080/13880209.2019.1702704] [PMID: 31873049]
[28]
Corbiere C, Liagre B, Terro F, Beneytout JL. Induction of antiproliferative effect by diosgenin through activation of p53, release of apoptosis-inducing factor (AIF) and modulation of caspase-3 activity in different human cancer cells. Cell Res 2004; 14(3): 188-96.
[http://dx.doi.org/10.1038/sj.cr.7290219] [PMID: 15225412]
[29]
Amiri S, Alijanpour S, Tirgar F, et al. NMDA receptors are involved in the antidepressant-like effects of capsaicin following amphetamine withdrawal in male mice. Neuroscience 2016; 329: 122-33.
[http://dx.doi.org/10.1016/j.neuroscience.2016.05.003] [PMID: 27167081]
[30]
Kordjazy N, Haj-Mirzaian A, Amiri S, Ostadhadi S, Amini-Khoei H, Dehpour AR. Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test. Pharmacol Biochem Behav 2016; 141: 1-9.
[http://dx.doi.org/10.1016/j.pbb.2015.11.009] [PMID: 26604075]
[31]
Anesti M, Stavropoulou N, Atsopardi K, Lamari FN, Panagopoulos NT, Margarity M. Effect of rutin on anxiety-like behavior and activity of acetylcholinesterase isoforms in specific brain regions of pentylenetetrazol-treated mice. Epilepsy Behav 2020; 102106632
[http://dx.doi.org/10.1016/j.yebeh.2019.106632] [PMID: 31747631]
[32]
Kraeuter A-K, Guest PC, Sarnyai Z. The elevated plus maze test for measuring anxiety-like behavior in rodents Pre-Clinical Models. Springer 2019; pp. 69-74.
[http://dx.doi.org/10.1007/978-1-4939-8994-2_4]
[33]
Pan W, Lyu K, Zhang H, et al. Attenuation of auditory mismatch negativity in serotonin transporter knockout mice with anxiety-related behaviors. Behav Brain Res 2020; 379112387
[http://dx.doi.org/10.1016/j.bbr.2019.112387] [PMID: 31783087]
[34]
Amini-Khoei H, Momeny M, Abdollahi A, et al. Tropisetron suppresses colitis-associated cancer in a mouse model in the remission stage. Int Immunopharmacol 2016; 36: 9-16.
[http://dx.doi.org/10.1016/j.intimp.2016.04.014] [PMID: 27104313]
[35]
Baracz SJ, Everett NA, Robinson KJ, Campbell GR, Cornish JL. Maternal separation changes maternal care, anxiety-like behaviour and expression of paraventricular oxytocin and corticotrophin-releasing factor immunoreactivity in lactating rats. J Neuroendocrinol 2020; 32(6)e12861
[http://dx.doi.org/10.1111/jne.12861] [PMID: 32490585]
[36]
Odeon MM, Acosta GB. Repeated maternal separation: Alcohol consumption, anxious behavior and corticosterone were reversed by a non-pharmacological treatment. Prog Neuropsychopharmacol Biol Psychiatry 2019; 95109726
[http://dx.doi.org/10.1016/j.pnpbp.2019.109726] [PMID: 31386878]
[37]
Jin S, Zhao Y, Jiang Y, et al. Anxiety-like behaviour assessments of adolescent rats after repeated maternal separation during early life. Neuroreport 2018; 29(8): 643-9.
[http://dx.doi.org/10.1097/WNR.0000000000001010] [PMID: 29561529]
[38]
Wang D, Levine JLS, Avila-Quintero V, Bloch M, Kaffman A. Systematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents. Transl Psychiatry 2020; 10(1): 174.
[http://dx.doi.org/10.1038/s41398-020-0856-0] [PMID: 32483128]
[39]
Šavikin-Fodulović K, et al. Diosgenin and phytosterols content in five callus lines of Dioscorea balcanica. Plant Sci 1998; 135(1): 63-7.
[http://dx.doi.org/10.1016/S0168-9452(98)00036-3]
[40]
Chiu C-S, Chiu YJ, Wu LY, et al. Diosgenin ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose. Am J Chin Med 2011; 39(3): 551-63.
[http://dx.doi.org/10.1142/S0192415X11009020] [PMID: 21598421]
[41]
Ho Y-J, Tai SY, Pawlak CR, Wang AL, Cheng CW, Hsieh MH. Behavioral and IL-2 responses to diosgenin in ovariectomized rats. Chin J Physiol 2012; 55(2): 91-100.
[PMID: 22559733]
[42]
Solati J, Salari A. Involvement of dorsal hippocampal NMDA-glutamatergic system in anxiety-related behaviors of rats. Neurochem J 2011; 5(3): 194.
[http://dx.doi.org/10.1134/S1819712411030081]
[43]
Bergink V, van Megen HJ, Westenberg HG. Glutamate and anxiety. Eur Neuropsychopharmacol 2004; 14(3): 175-83.
[http://dx.doi.org/10.1016/S0924-977X(03)00100-7] [PMID: 15056476]
[44]
Wiley JL, Cristello AF, Balster RL. Effects of site-selective NMDA receptor antagonists in an elevated plus-maze model of anxiety in mice. Eur J Pharmacol 1995; 294(1): 101-7.
[http://dx.doi.org/10.1016/0014-2999(95)00506-4] [PMID: 8788421]