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Gelsemium Low Doses Increases Bioenergetics and Neurite Outgrowth

Received: 18 February 2022    Accepted: 15 March 2022    Published: 23 March 2022
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Abstract

Gelsemium sempervirens (GS) is a traditional medicinal plant, previously identified as a remedy for a variety of psychological and behavioral symptoms of anxiety and depression at ultra-low doses. Changes in neural plasticity have been shown to play a significant role in the onset and development of those mental illnesses. Mitochondria play an extremely important role in the central nervous system by being the main energy producer through oxidative phosphorylation and being involved in the regulation of cell survival and death, as well as synaptic plasticity. Neurite outgrowth is the differentiation process by which neurons establish synapses through the protrusion of neurons and their extension. Because the effects of GS dilutions on mitochondrial function and neuroplasticity remain elusive, we aimed to investigate whether a treatment with GS at low doses (centesimal dilutions, C) improved bioenergetic parameters such as ATP production, mitochondrial respiration, cellular glycolysis, and neurite outgrowth. Nerve growth factor (NGF), which is known as a promotor of cell growth and survival, was used as a positive control. Our results demonstrate that GS dilutions (3C and 5C) efficiently ameliorated the bioenergetics of SH-SY5Y neuroblastoma cells by increasing cellular ATP level and mitochondrial respiration as well as promoting cell survival. In addition, GS dilutions significantly improved neurite extension in 2D as well as 3D culture models after 3 days of treatment. 3C and 5C dilutions showed similar functional effects to those obtained with the positive control nerve growth factor (NGF). These findings indicate that GS dilutions modulate mitochondrial bioenergetic phenotype and improve neurite formation. The mitochondrial function-improving properties of GS dilutions may represent one possible pathway contributing to its neuroprotective effects.

Published in American Journal of BioScience (Volume 10, Issue 2)
DOI 10.11648/j.ajbio.20221002.13
Page(s) 51-60
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Gelsemium Dilutions, Mitochondria, Bioenergetics, Neurite Outgrowth

References
[1] Barbancey, J., Pratique homéopathique en psycho-pathologie, in Pratique homéopathique en psycho-pathologie. 1977. p. 348-348.
[2] Jin, G. L., Y. P. Su, M. Liu, Y. Xu, J. Yang, K. J. Liao, and C. X. Yu, Medicinal plants of the genus Gelsemium (Gelsemiaceae, Gentianales)--a review of their phytochemistry, pharmacology, toxicology and traditional use. J Ethnopharmacol, 2014. 152 (1): p. 33-52.
[3] Gruenwald, J., T. Brendler, and C. Jaenicke, PDR for herbal medicines. 2007: Thomson, Reuters.
[4] Bellavite, P., C. Bonafini, and M. Marzotto, Experimental neuropharmacology of Gelsemium sempervirens: Recent advances and debated issues. J Ayurveda Integr Med, 2018. 9 (1): p. 69-74.
[5] Magnani, P., A. Conforti, E. Zanolin, M. Marzotto, and P. Bellavite, Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice. Psychopharmacology (Berl), 2010. 210 (4): p. 533-45.
[6] Rammal, H. and R. Soulimani, Effects of high doses of Gelsemium sempervirens L. on GABA receptor and on the cellular and humoral immunity in mice. Journal of Medicine and Medical Sciences Vol, 2010. 1: p. 40-44.
[7] Venard, C., N. Boujedaini, A. G. Mensah-Nyagan, and C. Patte-Mensah, Comparative Analysis of Gelsemine and Gelsemium sempervirens Activity on Neurosteroid Allopregnanolone Formation in the Spinal Cord and Limbic System. Evid Based Complement Alternat Med, 2011. 2011: p. 407617.
[8] Lejri, I., A. Grimm, M. Miesch, P. Geoffroy, A. Eckert, and A. G. Mensah-Nyagan, Allopregnanolone and its analog BR 297 rescue neuronal cells from oxidative stress-induced death through bioenergetic improvement. Biochim Biophys Acta Mol Basis Dis, 2017. 1863 (3): p. 631-642.
[9] Mattson, M. P., M. Gleichmann, and A. Cheng, Mitochondria in neuroplasticity and neurological disorders. Neuron, 2008. 60 (5): p. 748-66.
[10] Grimm, A. and A. Eckert, Brain aging and neurodegeneration: from a mitochondrial point of view. J Neurochem, 2017. 143 (4): p. 418-431.
[11] Lejri, I., A. Agapouda, A. Grimm, and A. Eckert, Mitochondria- and Oxidative Stress-Targeting Substances in Cognitive Decline-Related Disorders: From Molecular Mechanisms to Clinical Evidence. Oxid Med Cell Longev, 2019. 2019: p. 9695412.
[12] Drubin, D. G., S. C. Feinstein, E. M. Shooter, and M. W. Kirschner, Nerve growth factor-induced neurite outgrowth in PC12 cells involves the coordinate induction of microtubule assembly and assembly-promoting factors. J Cell Biol, 1985. 101 (5 Pt 1): p. 1799-807.
[13] Marzotto, M., D. Olioso, M. Brizzi, P. Tononi, M. Cristofoletti, and P. Bellavite, Extreme sensitivity of gene expression in human SH-SY5Y neurocytes to ultra-low doses of Gelsemium sempervirens. BMC Complement Altern Med, 2014. 14: p. 104.
[14] Jong, Y. I., S. K. Harmon, and K. L. O'Malley, Intracellular GPCRs Play Key Roles in Synaptic Plasticity. ACS Chem Neurosci, 2018. 9 (9): p. 2162-2172.
[15] Salud, O. M. d. l. and W. H. Organization, WHO guidelines on good agricultural and collection practices [GACP] for medicinal plants. 2003: World Health Organization.
[16] Unit, I. G. S. P. R. L., Red list Gelsemium. 2022.
[17] Leeser, O., Lehrbuch der Homöopathie, Pflanzliche Arzneistoffe II, Bd. IV. 1971, Haug Verlag Heidelberg.
[18] Collin, E., Précis de matière médicale. Octave Doin, Paris, 1908.
[19] von Bruchhausen, F., S. Ebel, and E. Hackenthal, Hagers Handbuch der Pharmazeutischen Praxis: Stoffe AK. 1999: Springer.
[20] Bentley, R., T. Stevens, and M. Thompson, The alkaloids of Gelsemium sempervirens. Part III. Sempervirine. Journal of the Chemical Society C: Organic, 1970 (6): p. 791-795.
[21] Schun, Y. and G. A. Cordell, 14β-hydroxygelsedine, a new oxindole alkaloid from Gelsemium sempervirens. Journal of Natural Products, 1985. 48 (5): p. 788-791.
[22] Palit, P., D. Mukherjee, and S. C. Mandal, Reconstituted mother tinctures of Gelsemium sempervirens L. improve memory and cognitive impairment in mice scopolamine-induced dementia model. J Ethnopharmacol, 2015. 159: p. 274-84.
[23] Zhang, J.-Y., N. Gong, J.-L. Huang, L.-C. Guo, and Y.-X. Wang, Gelsemine, a principal alkaloid from Gelsemium sempervirens Ait., exhibits potent and specific antinociception in chronic pain by acting at spinal α3 glycine receptors. PAIN®, 2013. 154 (11): p. 2452-2462.
[24] Venard, C., N. Boujedaini, P. Belon, A. Mensah-Nyagan, and C. Patte-Mensah, Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glycine and the alkaloidal analogs strychnine and gelsemine. Neuroscience, 2008. 153 (1): p. 154-161.
[25] European Pharmacopoeia. Ninth Edition, Supplement 9.4. EDQM, editor. Strasbourg, France: Council of Europe ed. 2017.
[26] Lejri, I., A. Grimm, F. Halle, M. Abarghaz, C. Klein, M. Maitre, M. Schmitt, J. J. Bourguignon, A. G. Mensah-Nyagan, F. Bihel, and A. Eckert, TSPO Ligands Boost Mitochondrial Function and Pregnenolone Synthesis. J Alzheimers Dis, 2019. 72 (4): p. 1045-1058.
[27] Vitet, L., C. Patte-Mensah, N. Boujedaini, A.-G. Mensah-Nyagan, and L. Meyer, Beneficial effects of Gelsemium-based treatment against paclitaxel-induced painful symptoms. Neurological Sciences, 2018. 39 (12): p. 2183-2196.
[28] Wendt, G., V. Kemmel, C. Patte-Mensah, B. Uring-Lambert, A. Eckert, M. J. Schmitt, and A. G. Mensah-Nyagan, Gamma-hydroxybutyrate, acting through an anti-apoptotic mechanism, protects native and amyloid-precursor-protein-transfected neuroblastoma cells against oxidative stress-induced death. Neuroscience, 2014. 263: p. 203-15.
[29] Grimm, A., I. Lejri, F. Halle, M. Schmitt, J. Gotz, F. Bihel, and A. Eckert, Mitochondria modulatory effects of new TSPO ligands in a cellular model of tauopathies. J Neuroendocrinol, 2020. 32 (1): p. e12796.
[30] Lejri, I., A. Grimm, and A. Eckert, Ginkgo biloba extract increases neurite outgrowth and activates the Akt/mTOR pathway. PLoS One, 2019. 14 (12): p. e0225761.
[31] Dutt, V., V. J. Dhar, and A. Sharma, Antianxiety activity of Gelsemium sempervirens. Pharm Biol, 2010. 48 (10): p. 1091-6.
[32] Trigo, D., M. B. Goncalves, and J. P. T. Corcoran, The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor beta signaling. FASEB J, 2019. 33 (6): p. 7225-7235.
[33] Morris, R. L. and P. J. Hollenbeck, The regulation of bidirectional mitochondrial transport is coordinated with axonal outgrowth. J Cell Sci, 1993. 104 (Pt 3): p. 917-27.
[34] Cartoni, R., M. W. Norsworthy, F. Bei, C. Wang, S. Li, Y. Zhang, C. V. Gabel, T. L. Schwarz, and Z. He, The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration. Neuron, 2017. 94 (3): p. 689.
[35] Meyer, L., N. Boujedaini, C. Patte-Mensah, and A. G. Mensah-Nyagan, Pharmacological effect of gelsemine on anxiety-like behavior in rat. Behavioural brain research, 2013. 253: p. 90-94.
[36] Yuan, Z., Z. Liang, J. Yi, X. Chen, R. Li, Y. Wu, J. Wu, and Z. Sun, Protective Effect of Koumine, an Alkaloid from Gelsemium Sempervirens, on Injury Induced by H(2)O(2) in IPEC-J2 Cells. Int J Mol Sci, 2019. 20 (3).
[37] Demangeat, J. L., Towards a rational insight into the paradox of homeopathy. Adv Complement Alt Med, 2018. 2 (2): p. 1-13.
[38] Van Wassenhoven, M., M. Goyens, E. Capieaux, P. Devos, and P. Dorfman, Nanoparticle characterisation of traditional homeopathically manufactured Cuprum metallicum and Gelsemium sempervirens medicines and controls. Homeopathy, 2018. 107 (04): p. 244-263.
[39] Van Wassenhoven, M., M. Goyens, M. Henry, J. Cumps, and P. Devos, Verification of nuclear magnetic resonance characterization of traditional homeopathically manufactured metal (Cuprum metallicum) and plant (Gelsemium sempervirens) medicines and controls. Homeopathy, 2021. 110 (01): p. 042-051.
[40] Van Wassenhoven, M., M. Goyens, M. Henry, E. Capieaux, and P. Devos, Nuclear Magnetic Resonance characterization of traditional homeopathically manufactured copper (Cuprum metallicum) and plant (Gelsemium sempervirens) medicines and controls. Homeopathy, 2017. 106 (04): p. 223-239.
[41] Demangeat, J.-L., Gas nanobubbles and aqueous nanostructures: the crucial role of dynamization. Homeopathy, 2015. 104 (02): p. 101-115.
[42] Demangeat, J.-L., Les hautes dilutions homéopathiques vues par la physique: arguments en faveur d’une nanomédecine. La Revue d'Homéopathie, 2020. 11 (1): p. 2-12.
Cite This Article
  • APA Style

    Imane Lejri, Amandine Grimm, Pascal Trempat, Naoual Boujedaini, Anne Eckert. (2022). Gelsemium Low Doses Increases Bioenergetics and Neurite Outgrowth. American Journal of BioScience, 10(2), 51-60. https://doi.org/10.11648/j.ajbio.20221002.13

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    ACS Style

    Imane Lejri; Amandine Grimm; Pascal Trempat; Naoual Boujedaini; Anne Eckert. Gelsemium Low Doses Increases Bioenergetics and Neurite Outgrowth. Am. J. BioScience 2022, 10(2), 51-60. doi: 10.11648/j.ajbio.20221002.13

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    AMA Style

    Imane Lejri, Amandine Grimm, Pascal Trempat, Naoual Boujedaini, Anne Eckert. Gelsemium Low Doses Increases Bioenergetics and Neurite Outgrowth. Am J BioScience. 2022;10(2):51-60. doi: 10.11648/j.ajbio.20221002.13

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  • @article{10.11648/j.ajbio.20221002.13,
      author = {Imane Lejri and Amandine Grimm and Pascal Trempat and Naoual Boujedaini and Anne Eckert},
      title = {Gelsemium Low Doses Increases Bioenergetics and Neurite Outgrowth},
      journal = {American Journal of BioScience},
      volume = {10},
      number = {2},
      pages = {51-60},
      doi = {10.11648/j.ajbio.20221002.13},
      url = {https://doi.org/10.11648/j.ajbio.20221002.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbio.20221002.13},
      abstract = {Gelsemium sempervirens (GS) is a traditional medicinal plant, previously identified as a remedy for a variety of psychological and behavioral symptoms of anxiety and depression at ultra-low doses. Changes in neural plasticity have been shown to play a significant role in the onset and development of those mental illnesses. Mitochondria play an extremely important role in the central nervous system by being the main energy producer through oxidative phosphorylation and being involved in the regulation of cell survival and death, as well as synaptic plasticity. Neurite outgrowth is the differentiation process by which neurons establish synapses through the protrusion of neurons and their extension. Because the effects of GS dilutions on mitochondrial function and neuroplasticity remain elusive, we aimed to investigate whether a treatment with GS at low doses (centesimal dilutions, C) improved bioenergetic parameters such as ATP production, mitochondrial respiration, cellular glycolysis, and neurite outgrowth. Nerve growth factor (NGF), which is known as a promotor of cell growth and survival, was used as a positive control. Our results demonstrate that GS dilutions (3C and 5C) efficiently ameliorated the bioenergetics of SH-SY5Y neuroblastoma cells by increasing cellular ATP level and mitochondrial respiration as well as promoting cell survival. In addition, GS dilutions significantly improved neurite extension in 2D as well as 3D culture models after 3 days of treatment. 3C and 5C dilutions showed similar functional effects to those obtained with the positive control nerve growth factor (NGF). These findings indicate that GS dilutions modulate mitochondrial bioenergetic phenotype and improve neurite formation. The mitochondrial function-improving properties of GS dilutions may represent one possible pathway contributing to its neuroprotective effects.},
     year = {2022}
    }
    

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  • TY  - JOUR
    T1  - Gelsemium Low Doses Increases Bioenergetics and Neurite Outgrowth
    AU  - Imane Lejri
    AU  - Amandine Grimm
    AU  - Pascal Trempat
    AU  - Naoual Boujedaini
    AU  - Anne Eckert
    Y1  - 2022/03/23
    PY  - 2022
    N1  - https://doi.org/10.11648/j.ajbio.20221002.13
    DO  - 10.11648/j.ajbio.20221002.13
    T2  - American Journal of BioScience
    JF  - American Journal of BioScience
    JO  - American Journal of BioScience
    SP  - 51
    EP  - 60
    PB  - Science Publishing Group
    SN  - 2330-0167
    UR  - https://doi.org/10.11648/j.ajbio.20221002.13
    AB  - Gelsemium sempervirens (GS) is a traditional medicinal plant, previously identified as a remedy for a variety of psychological and behavioral symptoms of anxiety and depression at ultra-low doses. Changes in neural plasticity have been shown to play a significant role in the onset and development of those mental illnesses. Mitochondria play an extremely important role in the central nervous system by being the main energy producer through oxidative phosphorylation and being involved in the regulation of cell survival and death, as well as synaptic plasticity. Neurite outgrowth is the differentiation process by which neurons establish synapses through the protrusion of neurons and their extension. Because the effects of GS dilutions on mitochondrial function and neuroplasticity remain elusive, we aimed to investigate whether a treatment with GS at low doses (centesimal dilutions, C) improved bioenergetic parameters such as ATP production, mitochondrial respiration, cellular glycolysis, and neurite outgrowth. Nerve growth factor (NGF), which is known as a promotor of cell growth and survival, was used as a positive control. Our results demonstrate that GS dilutions (3C and 5C) efficiently ameliorated the bioenergetics of SH-SY5Y neuroblastoma cells by increasing cellular ATP level and mitochondrial respiration as well as promoting cell survival. In addition, GS dilutions significantly improved neurite extension in 2D as well as 3D culture models after 3 days of treatment. 3C and 5C dilutions showed similar functional effects to those obtained with the positive control nerve growth factor (NGF). These findings indicate that GS dilutions modulate mitochondrial bioenergetic phenotype and improve neurite formation. The mitochondrial function-improving properties of GS dilutions may represent one possible pathway contributing to its neuroprotective effects.
    VL  - 10
    IS  - 2
    ER  - 

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Author Information
  • Neurobiology Lab for Brain Aging and Mental Health, Molecular & Cognitive Neuroscience, Transfaculty Research Platform, University of Basel, Basel, Switzerland

  • Neurobiology Lab for Brain Aging and Mental Health, Molecular & Cognitive Neuroscience, Transfaculty Research Platform, University of Basel, Basel, Switzerland

  • Laboratoire Boiron, Messimy, France

  • Laboratoire Boiron, Messimy, France

  • Neurobiology Lab for Brain Aging and Mental Health, Molecular & Cognitive Neuroscience, Transfaculty Research Platform, University of Basel, Basel, Switzerland

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