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Published in: BMC Complementary Medicine and Therapies 1/2018

Open Access 01-12-2018 | Research article

Total Saikosaponins of Bupleurum yinchowense reduces depressive, anxiety-like behavior and increases synaptic proteins expression in chronic corticosterine-treated mice

Authors: Xiuping Sun, Xianglei Li, Ruile Pan, Yanfeng Xu, Qiong Wang, Mingjing Song

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

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Abstract

Background

Bupleurum yinchowense Shan et Y. Li is widely used to treat depressive and anxiety disorders for hundreds of years in China. Total saikosaponins (TSS) is the major ingredient of Bupleurum yinchowense. A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and subsequent mammalian target of rapamycin (mTOR) signaling is responsible for synaptic maturation and may contribution to the synaptic alteration underlying depression. The aim of the study was to investigate the antidepressant-like and anxiolytic effect of TSS in chronic corticosterone-treated mice. The effect of TSS on synaptic proteins expression and AMPA receptor-mTOR signaling pathway alteration was also evaluated.

Methods

Dose-response effect of TSS (12.5, 25, 50 mg/kg) was investigated in forced swim test (FST) in ICR male mice. In the chronic corticosterine-treated model, TSS was given intragastrically once a day for 2 weeks and continued through the behavior testing period. Behavior tests and AMPA receptor related signaling pathway were investigated.

Results

TSS (25 and 50 mg/kg) decreased the immobility time in the FST when compared with the control group. TSS (25 mg/kg) showed antidepressant-like and anxiolytic effects in the chronic corticosterone treatment model in mice. TSS increased hippocampal synaptic proteins (synapsin-1 and postsynaptic density protein 95) expression. Immunohistochemistry analysis showed that TSS significantly increased the synapsin-1 expression in CA3 of hippocampus. TSS also increased hippocampal phosphorylation expression of GluR1 Ser 845 (AMPA receptor subunit) and its downstream regulators extracellular signaling-regulated kinase (ERK), protein kinase B (Akt) and mTOR.

Conclusion

TSS produces antidepressant-like and anxiolytic effects and increases synaptic proteins expression which may be mediated by induction of AMPA receptor and subsequent mTOR signaling pathway.
Literature
1.
go back to reference Yan H, Min H. Study of prescriptions containing Bupleurum as monarch for treatment of depression. Chin J Exp Tradit Med Formulae. 2010;17:247–9. Yan H, Min H. Study of prescriptions containing Bupleurum as monarch for treatment of depression. Chin J Exp Tradit Med Formulae. 2010;17:247–9.
2.
go back to reference Sun X, SZ, Li T, Pan R, Liu X, Bu L, Kong L. Antidepressant-like effects of total saikosaponins of Bupleurum yinchowense in mice. J Med Plants Res. 2012;6(26):4308–16. Sun X, SZ, Li T, Pan R, Liu X, Bu L, Kong L. Antidepressant-like effects of total saikosaponins of Bupleurum yinchowense in mice. J Med Plants Res. 2012;6(26):4308–16.
4.
go back to reference Zhang H, Etherington LA, Hafner AS, Belelli D, Coussen F, Delagrange P, Chaouloff F, Spedding M, Lambert JJ, Choquet D, et al. Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule. Mol Psychiatry. 2013;18(4):471–84.CrossRefPubMed Zhang H, Etherington LA, Hafner AS, Belelli D, Coussen F, Delagrange P, Chaouloff F, Spedding M, Lambert JJ, Choquet D, et al. Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule. Mol Psychiatry. 2013;18(4):471–84.CrossRefPubMed
5.
go back to reference Walker AK, Budac DP, Bisulco S, Lee AW, Smith RA, Beenders B, Kelley KW, Dantzer R. NMDA receptor blockade by ketamine abrogates lipopolysaccharide-induced depressive-like behavior in C57BL/6J mice. Neuropsychopharmacology. 2013;38(9):1609–16.CrossRefPubMedPubMedCentral Walker AK, Budac DP, Bisulco S, Lee AW, Smith RA, Beenders B, Kelley KW, Dantzer R. NMDA receptor blockade by ketamine abrogates lipopolysaccharide-induced depressive-like behavior in C57BL/6J mice. Neuropsychopharmacology. 2013;38(9):1609–16.CrossRefPubMedPubMedCentral
6.
go back to reference Akinfiresoye L, Tizabi Y. Antidepressant effects of AMPA and ketamine combination: role of hippocampal BDNF, synapsin, and mTOR. Psychopharmacology. 2013;230(2):291–8.CrossRefPubMed Akinfiresoye L, Tizabi Y. Antidepressant effects of AMPA and ketamine combination: role of hippocampal BDNF, synapsin, and mTOR. Psychopharmacology. 2013;230(2):291–8.CrossRefPubMed
7.
go back to reference Ignacio ZM, Reus GZ, Arent CO, Abelaira HM, Pitcher MR, Quevedo J. New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs. Br J Clin Pharmacol. 2015;82(5):1280–90.CrossRef Ignacio ZM, Reus GZ, Arent CO, Abelaira HM, Pitcher MR, Quevedo J. New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs. Br J Clin Pharmacol. 2015;82(5):1280–90.CrossRef
8.
go back to reference Zhou W, Wang N, Yang C, Li XM, Zhou ZQ, Yang JJ. Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex. Eur Psychiatry. 2014;29(7):419–23.CrossRefPubMed Zhou W, Wang N, Yang C, Li XM, Zhou ZQ, Yang JJ. Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex. Eur Psychiatry. 2014;29(7):419–23.CrossRefPubMed
9.
go back to reference Chen KT, Tsai MH, Wu CH, Jou MJ, Wei IH, Huang CC. AMPA receptor-mTOR activation is required for the antidepressant-like effects of sarcosine during the forced swim test in rats: insertion of AMPA receptor may play a role. Front Behav Neurosci. 2015;9:162.PubMedPubMedCentral Chen KT, Tsai MH, Wu CH, Jou MJ, Wei IH, Huang CC. AMPA receptor-mTOR activation is required for the antidepressant-like effects of sarcosine during the forced swim test in rats: insertion of AMPA receptor may play a role. Front Behav Neurosci. 2015;9:162.PubMedPubMedCentral
10.
go back to reference Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005;4(2):141–94.CrossRefPubMed Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005;4(2):141–94.CrossRefPubMed
11.
go back to reference Le Dantec Y, Hache G, Guilloux JP, Guiard BP, David DJ, Adrien J, Escourrou P. NREM sleep hypersomnia and reduced sleep/wake continuity in a neuroendocrine mouse model of anxiety/depression based on chronic corticosterone administration. Neuroscience. 2014;274:357–68.CrossRefPubMed Le Dantec Y, Hache G, Guilloux JP, Guiard BP, David DJ, Adrien J, Escourrou P. NREM sleep hypersomnia and reduced sleep/wake continuity in a neuroendocrine mouse model of anxiety/depression based on chronic corticosterone administration. Neuroscience. 2014;274:357–68.CrossRefPubMed
12.
go back to reference Crupi R, Mazzon E, Marino A, La Spada G, Bramanti P, Cuzzocrea S, Spina E. Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice. J Pineal Res. 2010;49:123–9.PubMed Crupi R, Mazzon E, Marino A, La Spada G, Bramanti P, Cuzzocrea S, Spina E. Melatonin treatment mimics the antidepressant action in chronic corticosterone-treated mice. J Pineal Res. 2010;49:123–9.PubMed
13.
go back to reference Tse YC, Bagot RC, Wong TP. Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone. Front Cell Neurosci. 2012;6:9.CrossRefPubMedPubMedCentral Tse YC, Bagot RC, Wong TP. Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone. Front Cell Neurosci. 2012;6:9.CrossRefPubMedPubMedCentral
14.
go back to reference Li Z-Y, Guo Z, Liu Y-M, Liu X-M, Chang Q, Liao Y-h, Pan R-L. Neuroprotective effects of Total Saikosaponins of Bupleurum yinchowense on corticosterone-induced apoptosis in PC12 cells. J Ethnopharmacol. 2013;148(3):794–803.CrossRefPubMed Li Z-Y, Guo Z, Liu Y-M, Liu X-M, Chang Q, Liao Y-h, Pan R-L. Neuroprotective effects of Total Saikosaponins of Bupleurum yinchowense on corticosterone-induced apoptosis in PC12 cells. J Ethnopharmacol. 2013;148(3):794–803.CrossRefPubMed
15.
go back to reference Porsolt R, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977;229(2):327–36.PubMed Porsolt R, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977;229(2):327–36.PubMed
16.
go back to reference Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463(1–3):3–33.CrossRefPubMed Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463(1–3):3–33.CrossRefPubMed
17.
go back to reference Calabrese EJ. An assessment of anxiolytic drug screening tests: hormetic dose responses predominate. Crit Rev Toxicol. 2008;38(6):489–542.CrossRefPubMed Calabrese EJ. An assessment of anxiolytic drug screening tests: hormetic dose responses predominate. Crit Rev Toxicol. 2008;38(6):489–542.CrossRefPubMed
18.
go back to reference Stedenfeld KA, Clinton SM, Kerman IA, Akil H, Watson SJ, Sved AF. Novelty-seeking behavior predicts vulnerability in a rodent model of depression. Physiol Behav. 2011;103(2):210–6.CrossRefPubMedPubMedCentral Stedenfeld KA, Clinton SM, Kerman IA, Akil H, Watson SJ, Sved AF. Novelty-seeking behavior predicts vulnerability in a rodent model of depression. Physiol Behav. 2011;103(2):210–6.CrossRefPubMedPubMedCentral
19.
go back to reference Yang J-S, Zhang N, Song M-J, Sun X-P. Antidepressant-like effect and learning and memory improvement of Bupleurum yinchowense total saikosaponins and its possible mechanism in mice. Chin J Exp Tradit Med Formulae. 2016;24(22):134–9. Yang J-S, Zhang N, Song M-J, Sun X-P. Antidepressant-like effect and learning and memory improvement of Bupleurum yinchowense total saikosaponins and its possible mechanism in mice. Chin J Exp Tradit Med Formulae. 2016;24(22):134–9.
20.
go back to reference Cai Z-Z, Xu G-Y, Dong H-Y. Protective effect of Saikosaponin on the hippocampal neuron of depression model rats. Med Innov China. 2016;13(03):28–30. Cai Z-Z, Xu G-Y, Dong H-Y. Protective effect of Saikosaponin on the hippocampal neuron of depression model rats. Med Innov China. 2016;13(03):28–30.
21.
go back to reference Darcet F, Mendez-David I, Tritschler L, Gardier AM, Guilloux JP, David DJ. Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression. Front Behav Neurosci. 2014;8:136.CrossRefPubMedPubMedCentral Darcet F, Mendez-David I, Tritschler L, Gardier AM, Guilloux JP, David DJ. Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression. Front Behav Neurosci. 2014;8:136.CrossRefPubMedPubMedCentral
22.
go back to reference Quesseveur G, Portal B, Basile JA, Ezan P, Mathou A, Halley H, Leloup C, Fioramonti X, Deglon N, Giaume C, et al. Attenuated levels of hippocampal Connexin 43 and its phosphorylation correlate with antidepressant- and anxiolytic-like activities in mice. Front Cell Neurosci. 2015;9:490.CrossRefPubMedPubMedCentral Quesseveur G, Portal B, Basile JA, Ezan P, Mathou A, Halley H, Leloup C, Fioramonti X, Deglon N, Giaume C, et al. Attenuated levels of hippocampal Connexin 43 and its phosphorylation correlate with antidepressant- and anxiolytic-like activities in mice. Front Cell Neurosci. 2015;9:490.CrossRefPubMedPubMedCentral
23.
go back to reference Hirschfeld RMA. The comorbidity of major depression and anxiety disorders: recognition and Management in Primary Care. Prim Care Companion J Clin Psychiatry. 2001;3(6):244–54.CrossRefPubMedPubMedCentral Hirschfeld RMA. The comorbidity of major depression and anxiety disorders: recognition and Management in Primary Care. Prim Care Companion J Clin Psychiatry. 2001;3(6):244–54.CrossRefPubMedPubMedCentral
24.
go back to reference Wu Z, Fang Y. Comorbidity of depressive and anxiety disorders: challenges in diagnosis and assessment. Shanghai Arch Psychiatry. 2014;26(4):227–31.PubMedPubMedCentral Wu Z, Fang Y. Comorbidity of depressive and anxiety disorders: challenges in diagnosis and assessment. Shanghai Arch Psychiatry. 2014;26(4):227–31.PubMedPubMedCentral
25.
go back to reference Coplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: psychosocial and pharmacological approaches. World J Psychiatry. 2015;5(4):366–78.CrossRefPubMedPubMedCentral Coplan JD, Aaronson CJ, Panthangi V, Kim Y. Treating comorbid anxiety and depression: psychosocial and pharmacological approaches. World J Psychiatry. 2015;5(4):366–78.CrossRefPubMedPubMedCentral
26.
go back to reference Kellner M, Porseryd T, Hallgren S, Porsch-Hallstrom I, Hansen SH, Olsen KH. Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus). Aquat Toxicol. 2016;173:19–28.CrossRefPubMed Kellner M, Porseryd T, Hallgren S, Porsch-Hallstrom I, Hansen SH, Olsen KH. Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus). Aquat Toxicol. 2016;173:19–28.CrossRefPubMed
27.
go back to reference Grizzell JA, Iarkov A, Holmes R, Mori T, Echeverria V. Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice. Behav Brain Res. 2014;268(0):55–65.CrossRefPubMed Grizzell JA, Iarkov A, Holmes R, Mori T, Echeverria V. Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice. Behav Brain Res. 2014;268(0):55–65.CrossRefPubMed
28.
go back to reference Renard J, Vitalis T, Rame M, Krebs M-O, Lenkei Z, Le Pen G, Jay TM. Chronic cannabinoid exposure during adolescence leads to long-term structural and functional changes in the prefrontal cortex. Eur Neuropsychopharmacol. 2016;26(1):55–64.CrossRefPubMed Renard J, Vitalis T, Rame M, Krebs M-O, Lenkei Z, Le Pen G, Jay TM. Chronic cannabinoid exposure during adolescence leads to long-term structural and functional changes in the prefrontal cortex. Eur Neuropsychopharmacol. 2016;26(1):55–64.CrossRefPubMed
29.
go back to reference Orlowski D, Elfving B, Muller HK, Wegener G, Bjarkam CR. Wistar rats subjected to chronic restraint stress display increased hippocampal spine density paralleled by increased expression levels of synaptic scaffolding proteins. Stress. 2012;15(5):514–23.CrossRefPubMed Orlowski D, Elfving B, Muller HK, Wegener G, Bjarkam CR. Wistar rats subjected to chronic restraint stress display increased hippocampal spine density paralleled by increased expression levels of synaptic scaffolding proteins. Stress. 2012;15(5):514–23.CrossRefPubMed
30.
go back to reference Du Y-W, Wang Y-L, Yin L, Zhao X-M, Qin S-L, Zhao Y-L. Effects of CHSG powder on ERK and P - ERK in Hippocampus of rats with liver - qi stagnation. Chin Arch Tradit Chin Med. 2012;30(06):1367–9. Du Y-W, Wang Y-L, Yin L, Zhao X-M, Qin S-L, Zhao Y-L. Effects of CHSG powder on ERK and P - ERK in Hippocampus of rats with liver - qi stagnation. Chin Arch Tradit Chin Med. 2012;30(06):1367–9.
31.
go back to reference Zhang X-J, Dong H-Y, Sun Y-R, Lin C-R, Li X-Y. Effect of ChaihuShugan powder on apoptosis in hippocampal CA3 area of Depressive rats. Lishizhen Med Materia Medica Res. 2011;22(01):43–5. Zhang X-J, Dong H-Y, Sun Y-R, Lin C-R, Li X-Y. Effect of ChaihuShugan powder on apoptosis in hippocampal CA3 area of Depressive rats. Lishizhen Med Materia Medica Res. 2011;22(01):43–5.
32.
go back to reference Gong WG, Wang YJ, Zhou H, Li XL, Bai F, Ren QG, Zhang ZJ. Citalopram ameliorates synaptic plasticity deficits in different cognition-associated brain regions induced by social isolation in middle-aged rats. Mol Neurobiol. 2017;54(3):1927–38.CrossRefPubMed Gong WG, Wang YJ, Zhou H, Li XL, Bai F, Ren QG, Zhang ZJ. Citalopram ameliorates synaptic plasticity deficits in different cognition-associated brain regions induced by social isolation in middle-aged rats. Mol Neurobiol. 2017;54(3):1927–38.CrossRefPubMed
33.
go back to reference Voleti B, Navarria A, Liu RJ, Banasr M, Li N, Terwilliger R, Sanacora G, Eid T, Aghajanian G, Duman RS. Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses. Biol Psychiatry. 2013;74(10):742–9.CrossRefPubMed Voleti B, Navarria A, Liu RJ, Banasr M, Li N, Terwilliger R, Sanacora G, Eid T, Aghajanian G, Duman RS. Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses. Biol Psychiatry. 2013;74(10):742–9.CrossRefPubMed
34.
go back to reference Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959–64.CrossRefPubMedPubMedCentral Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959–64.CrossRefPubMedPubMedCentral
35.
go back to reference Dwyer JM, Duman RS. Activation of mammalian target of rapamycin and synaptogenesis: role in the actions of rapid-acting antidepressants. Biol Psychiatry. 2013;73(12):1189–98.CrossRefPubMedPubMedCentral Dwyer JM, Duman RS. Activation of mammalian target of rapamycin and synaptogenesis: role in the actions of rapid-acting antidepressants. Biol Psychiatry. 2013;73(12):1189–98.CrossRefPubMedPubMedCentral
36.
go back to reference Opal MD, Klenotich SC, Morais M, Bessa J, Winkle J, Doukas D, Kay LJ, Sousa N, Dulawa SM. Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. Mol Psychiatry. 2014;19(10):1106–14.CrossRefPubMed Opal MD, Klenotich SC, Morais M, Bessa J, Winkle J, Doukas D, Kay LJ, Sousa N, Dulawa SM. Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. Mol Psychiatry. 2014;19(10):1106–14.CrossRefPubMed
Metadata
Title
Total Saikosaponins of Bupleurum yinchowense reduces depressive, anxiety-like behavior and increases synaptic proteins expression in chronic corticosterine-treated mice
Authors
Xiuping Sun
Xianglei Li
Ruile Pan
Yanfeng Xu
Qiong Wang
Mingjing Song
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2186-9

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