Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-14T20:07:21.009Z Has data issue: false hasContentIssue false

Standardised ginseng extract G115® potentiates the antidepressant-like properties of fluoxetine in the forced swim test

Published online by Cambridge University Press:  22 January 2021

Dylan J. Terstege
Affiliation:
Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada
Debra S. MacDonald
Affiliation:
Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada
R. Andrew Tasker*
Affiliation:
Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada Translational Neuropsychiatry Unit, Clinical Medicine, Aarhus Universitet, Aarhus, Denmark
*
Author for correspondence: R. Andrew Tasker, Email: tasker@upei.ca

Abstract

Objective:

Ginsenosides, biologically active components of the root of Panax ginseng, have been reported to have therapeutic benefits in a number of disease states including psychiatric conditions such as major depressive disorder. Our objective was to determine if a standardised commercial ginseng extract, G115®, could reduce the signs of behavioural despair commonly observed in animal models of depression either alone or in combination with the selective serotonin reuptake inhibitor (SSRI) fluoxetine.

Methods:

Male Sprague-Dawley (SD) rats (N = 51) were divided into four groups: vehicle control, G115® ginseng root extract, fluoxetine and fluoxetine plus G115®. Rats were trained to voluntarily consume treatments twice daily for 14 days and were then tested in an open field (OF), elevated plus maze (EPM) and forced swim test (FST). Post-mortem hippocampal and prefrontal cortex tissue was analysed for expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) by western blot.

Results:

One-way Analysis of Variance revealed no significant group differences in the OF or plus-maze performance on any variable examined. In the FST, fluoxetine significantly reduced immobility time and increased latency to immobility. The effects of fluoxetine were further significantly potentiated by co-administration of G115®. Post-mortem tissue analysis revealed significant group differences in BDNF expression in the left hippocampus and left prefrontal cortex without any accompanying changes in TrkB expression.

Conclusions:

We conclude that oral G115® significantly potentiates the antidepressant-like effect of fluoxetine in the FST in the absence of potentially confounding effects on locomotion and anxiety.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

#

Current Address: Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

References

Abbas, G, Naqvi, S and Dar, A (2012) Comparison of monoamine reuptake inhibitors for the immobility time and serotonin levels in the hippocampus and plasma of sub-chronically forced swim stressed rats. Pakistan Journal of Pharmaceutical Sciences 25, 441445.Google ScholarPubMed
Adachi, M, Barrot, M, Autry, AE, Theobold, D and Monteggia, LM (2008) Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biological Psychiatry 63, 642649.CrossRefGoogle ScholarPubMed
Aso, E, Ozaita, A, Valdizan, EM, Ledent, C, Pazos, A, Maldonaldo, R and Valverde, O (2008) BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. Journal of Neurochemistry 105, 565572.CrossRefGoogle ScholarPubMed
Badowska-Szalewska, E, Spodnik, E, Klejbor, I and Morys, J (2010) Effects of chronic forced swim stress on hippocampal brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) immunoreactive cells in juvenile and aged rats. Acta Neurobiologiae Experimentalis 70, 370381.Google ScholarPubMed
Bourin, M, Fiocco, AJ and Clenet, F (2001) How valuable are animal models in defining antidepressant activity ?. Human Psychopharmacology 16, 921.CrossRefGoogle ScholarPubMed
Boonlert, W, Benya-Aphikul, H, Welbat, JU and Rodsiri, R (2017) Ginseng extract G115 attenuates ethanol-induced depression in mice by increasing brain BDNF levels. Nutrients 9, 931; doi: 10.3390/nu9090931 CrossRefGoogle ScholarPubMed
Castagne, V, Moser, P, Roux, S and Porsolt, RD (2011) Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Current Protocols in Pharmacology 5: Unit 5.8. doi: 10.1002/0471141755.ph0508s49 Google Scholar
Cipriani, A, Zhou, X, Del Giovane, C, Hetrick, SE, Qin, B, Whittington, C, Coghill, D, Zhang, Y, Hazell, P, Leucht, S, Cuijpers, P, Pu, J, Cohen, D, Ravindran, AV, Liu, Y, Michael, KD, Yang, L, Liu, L and Xie, P (2016) Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet 388, 881890.CrossRefGoogle ScholarPubMed
Costello, JE, Erkanli, A and Angold, A. (2006) Is there an epidemic of child or adolescent depression ?. Journal of Child Psychology and Psychiatry 47, 12631271.Google Scholar
Cryan, JF, Valentino, RJ and Lucki, I (2005) Assessing substrates underlying behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews 29, 547569.CrossRefGoogle ScholarPubMed
Cui, J-F (1995) Identification and quantification of ginsenosides in various commercial ginseng preparations. European Journal of Pharmaceutical Sciences 3, 7785.CrossRefGoogle Scholar
Cui, J, Jiang, L and Xiang, H (2011) Ginsenoside Rb3 exerts anti-depressant-like effects in several animal models. Journal of Psychopharmacology 26, 697713.CrossRefGoogle Scholar
Deyama, S and Duman, RS (2020) Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine. Pharmacology Biochemistry and Behavior 188, 172837. doi: 10.1016/j.pbb.2019.172837 CrossRefGoogle ScholarPubMed
Ferrari, AJ, Somerville, AJ, Baxter, AJ, Norman, R, Patten, SB, Vos, T and Whiteford, HA (2013) Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychological Medicine 43, 471481.CrossRefGoogle ScholarPubMed
Jiang, B, Xiong, Z, Yang, J, Wang, W, Wang, Y, Hu, ZL, Wang, F and Chen, JC (2012) Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus. British Journal of Pharmacology 166, 18721887.CrossRefGoogle ScholarPubMed
Jin, Y, Cui, R, Zhao, L, Fan, J and Li, B (2019) Mechanisms of Panax ginseng action as an antidepressant. Cell Proliferation 52: doi: 10.111/cpr.12696 CrossRefGoogle ScholarPubMed
Kohler, S, Cierpinsky, K, Kronenberg, G and Adli, M (2015) The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants. Journal of Psychopharmacology 30, 1322.CrossRefGoogle ScholarPubMed
Lee, KH, Bahk, W-M, Lee, S-J and Pae, C-U (2020) Effectiveness and tolerability of Korean red ginseng augmentation in major depressive disorder patients with difficult-to-treat in routine practice. Clinical Psychopharmacology and Neuroscience 18, 621626.CrossRefGoogle ScholarPubMed
Liang, W, Ge, S, Yang, L, Yang, M, Ye, Z, Yan, M, Du, J and Luo, Z (2010) Ginsenosides Rb1 and Rg1 promote proliferation and expression of neurotrophic factors in primary Schwann cell cultures. Brain Research 1357, 1925.CrossRefGoogle ScholarPubMed
Lu, ZF, Shen, YX, Zhang, P, Xu, YJ, Fan, ZH, Cheng, MH and Dong, QR (2010) Ginsenoside Rg1 promotes proliferation and neurotrophin expression of olfactory ensheathing cells. Journal of Asian Natural Products Research 12, 265272.CrossRefGoogle ScholarPubMed
Mondal, AC and Fatima, M (2019) Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment. International Journal of Neuroscience 129, 283296.CrossRefGoogle ScholarPubMed
Mrazek, DA, Hornberger, JC, Altar, CA and Degtiar, I (2014) A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996–2013. Psychiatric Services 65, 977987.CrossRefGoogle ScholarPubMed
Nestler, EJ, Barrot, M, DiLeone, RJ, Eisch, AJ, Gold, SJ and Monteggia, LM (2002) Neurobiology of depression. Neuron 34, 1325.CrossRefGoogle ScholarPubMed
Petit-Demouliere, B, Chenu, F and Bourin, M (2005) Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology 177, 245255.CrossRefGoogle ScholarPubMed
Porsolt, RD, Anton, G, Blavet, N and Jalfre, M (1978) Behavioural despair in rats: a new model sensitive to antidepressant treatments. European Journal of Pharmacology 47, 379391.CrossRefGoogle ScholarPubMed
Qi, X, Ignatova, S, Luo, G, Liang, Q, Jun, FW, Wang, Y and Sutherland, I (2010) Preparative isolation and purification of ginsenosides Rf, Re, Rd, and Rb1 from the roots of Panax ginseng with a salt-containing solvent system and flow step-gradient by high performance counter-current chromatography coupled with an evaporative light scattering detector. Journal of Chromatography A 1217, 19952001.CrossRefGoogle ScholarPubMed
Schuch, JJJ, Roest, AM, Nolen, WA, Penninx, BWJH and de Jonge, P (2013) Gender differences in major depressive disorder: results from the Netherlands study of depression and anxiety. Journal of Affective Disorders. https://doi.org/10.1016/j.jad.2013.12.011 Google ScholarPubMed
Seibenhener, ML and Wooten, MC. (2015) Use of the open field maze to measure locomotor and anxiety-like behavior in mice. Journal of Visualized Experiments 96, e52434. doi: 10.3791/52434 Google Scholar
Seligman, MEP and Maier, SF (1967) Failure to escape traumatic shock. Journal of Experimental Psychology 74, 19.CrossRefGoogle ScholarPubMed
Shi, Y-Q, Huang, T-W, Chen, L-M, Pan, X-D, Zhang, J, Zhu, Y-G and Chen, X-C (2010) Ginsenoside Rg1 attenuates amyloid-beta content, regulates PKA/CREB activity, and improves cognitive performance in SAMP8 mice. Journal of Alzheimers Disease 19, 977989.CrossRefGoogle ScholarPubMed
Shirayama, Y, Chen, AC, Nakagawa, S, Russell, DS and Duman, RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. Journal of Neuroscience 22, 32513261.CrossRefGoogle ScholarPubMed
Slattery, DA and Cryan, JF (2012) Using the forced swim test to assess antidepressant-like activity in rodents. Nature Protocols 7, 10091014.CrossRefGoogle ScholarPubMed
Walf, AA and Frye, CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols 2, 322328.CrossRefGoogle ScholarPubMed
Wegener, G, Matthe, AA and Neumann, ID (2012) Selectively bred rodents as models of depression and anxiety. Current Topics in Behavioral Neurosciences 12, 139187.CrossRefGoogle ScholarPubMed
World Health Organization, Depression and Other Common Mental Disorders – Global Health Estimates (2017). Available at https://www.who.int/mental_health/management/depression/prevalence_global_health_estimates/en/ (accessed 8 October 2019).Google Scholar
Yamada, N, Araki, H and Yoshimura, H (2011) Identification of antidepressant-like ingredients in ginseng root (Panax ginseng C.A. Meyer) using a menopausal depressive-like state in female mice: participation of 5-HT2A receptors. Psychopharmacology (Berlin) 216, 589599.CrossRefGoogle Scholar
You, Z, Yao, Q, Shen, J, Gu, Z, Xu, H, Wu, Z, Chen, C and Li, L (2017) Antidepressant-like effects of Ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade. Journal of Natural Medicines 71, 367379.CrossRefGoogle ScholarPubMed
Zhang, H, Zhou, Z, Chen, Z, Zhong, Z and Zhong, L (2017) Ginsenoside Rg3 exerts anti-depressive effect on an NMDA-treated cell model and a chronic mild stress animal model. Journal of Pharmacological Sciences 134, 4554.CrossRefGoogle Scholar
Supplementary material: PDF

Terstege et al. supplementary material

Terstege et al. supplementary material 1

Download Terstege et al. supplementary material(PDF)
PDF 256.8 KB
Supplementary material: File

Terstege et al. supplementary material

Terstege et al. supplementary material 2

Download Terstege et al. supplementary material(File)
File 161.1 KB