The antidepressive activity of tablets containing the dry peony root extract, L-tryptophan, and glycine in the model of reserpine-induced depression in rats

Authors

DOI:

https://doi.org/10.24959/nphj.26.212

Keywords:

reserpine; dry extract of peony roots; L-tryptophan; glycine; antidepressive effect.

Abstract

Aim. To study the antidepressive properties of new combined tablets containing the dry peony root extract, L-tryptophan, and glycine in the model of reserpine-induced depression in rats.

Materials and methods. The study was conducted on 40 white outbred male rats weighing 200–250 g. A depression-like state was induced by the intraperitoneal administration of reserpine (4 mg/kg). The test drug was administered transbuccally in the dose of 35 mg/kg for four days. Imipramine (15 mg/kg) was used as a reference drug. The antidepressive activity was assessed by measuring rectal temperature, blepharoptosis, behavior in the open field test, and performance in the Porsolt forced swimming test. The statistical processing was performed using the Student’s t-test with significance set at p ≤ 0.05.

Results. The reserpine administration caused the development of typical depression-like manifestations, including hypothermia, pronounced blepharoptosis, reduced locomotor and exploratory activity, and increased immobility duration in the forced swimming test. The test drug significantly attenuated hypothermia and reduced the severity of blepharoptosis. In the open field test, a partial restoration of the locomotor and exploratory activity was observed compared to the pathology control group. In the Porsolt test, the latency to immobility significantly increased by 14 %, while the total and mean immobility duration decreased by 34 % and 44 %, respectively (p < 0.05). The results observed may be due to the combined action of the drug components: L-tryptophan as a serotonin precursor, glycine as a modulator of the glutamatergic neurotransmission and a neuroprotective agent, as well as biologically active compounds of the peony extract with the potential sedative and neuromodulatory activity.

Conclusions. The new combined tablets containing the dry peony root extract, L-tryptophan, and glycine demonstrate the antidepressive-like activity in rats in the reserpine-induced depression model. The drug significantly attenuates the major behavioral and somato-vegetative manifestations of the depressive state although its effect is less pronounced than that of imipramine. These findings substantiate the feasibility of further preclinical studies.

References

  1. Malhi, G. S., & Mann, J. J. (2018). Depression. Lancet, 392(10161), 2299–2312. http://doi.org/10.1016/S0140-6736(18)31948-2
  2. Walker, E. R., McGee, R. E., & Druss, B. G. (2015). Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis. JAMA Psychiatry, 72(4), 334–341. http://doi.org/10.1001/jamapsychiatry.2014.2502
  3. Blackmore, R., Gray, K. M., Boyle, J. A., Fazel, M., Ranasinha, S., Fitzgerald, G., Misso, M., & Gibson-Helm, M. (2020). Systematic Review and Meta-analysis: The Prevalence of Mental Illness in Child and Adolescent Refugees and Asylum Seekers. Journal of the American Academy of Child Adolescent Psychiatry, 59(6), 705–714. http://doi.org/10.1016/j.jaac.2019.11.011
  4. Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., Egger, M., Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J. P. A., & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet, 391(10128), 1357–1366. http://doi.org/10.1016/S0140-6736(17)32802-7
  5. Almulla, A. F., Thipakorn, Y., Vasupanrajit, A., Tunvirachaisakul, C., Oxenkrug, G., Al-Hakeim, H. K, & Maes, M. (2022). The Tryptophan Catabolite or Kynurenine Pathway in a Major Depressive Episode with Melancholia, Psychotic Features and Suicidal Behaviors: A Systematic Review and Meta-Analysis. Cells, 11(19), 3112. http://doi.org/10.3390/cells11193112
  6. Jenkins, T. A., Nguyen, J. C. D., Polglaze, K. E., & Bertrand, P. P. (2016). Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8(1), 56. http://doi.org/10.3390/nu8010056
  7. Wang, X.-L., Wang, Y.-T., Guo, Z.-Y., Zhang, N.-N., Wang, Y.-Y., Hu, D., Wang, Z.-Z., & Zhang, Y. (2022). Efficacy of paeoniflorin on models of depression: A systematic review and meta-analysis of rodent studies. Journal of Ethnopharmacology, 290, 115067. http://doi.org/10.1016/j.jep.2022.115067
  8. Du, W., Liang, X., Wang, S., Lee, P., & Zhang, Y. (2020). The Underlying Mechanism of Paeonia lactiflora Pall. in Parkinson’s Disease Based on a Network Pharmacology Approach. Front. Pharmacol., 11, 581984. http://doi.org/10.3389/fphar.2020.581984
  9. Planchez, B., Surget, A., & Belzung, C. (2019). Animal models of major depression: drawbacks and challenges. J. Neural. Transm., 126(11), 1383–1408. http://doi.org/10.1007/s00702-019-02084-y
  10. Cryan, J. F., & Mombereau, C. (2004). In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol. Psychiatry, 9(4), 326–357. http://doi.org/10.1038/sj.mp.4001457
  11. Onishi, H., & Sakata, O. (2018). Absorption behavior of etilefrine after buccal administration in rats. International Journal of Pharmaceutics, 550(1-2), 14–23. http://doi.org/10.1016/j.ijpharm.2018.08.009
  12. Bahraminejad, S., & Almoazen, H. (2025). Sublingual and Buccal Delivery: A Historical and Scientific Prescriptive. Pharmaceutics, 17(8), 1073. http://doi.org/10.3390/pharmaceutics17081073
  13. Cryan, J. F., & Mombereau, C. (2004). In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Molecular Psychiatry, 9(4), 326–357. http://doi.org/10.1038/sj.mp.4001457
  14. Krishnan, V., & Nestler, E. J. (2008). The molecular neurobiology of depression. Nature, 455(7215), 894–902. http://doi.org/10.1038/nature07455
  15. Willner, P. (2005). Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology, 52(2), 90–110. http://doi.org/10.1159/000087097
  16. Porsolt, R. D., Le Pichon, M., & Jalfre, M. (1977). Depression: a new animal model sensitive to antidepressive treatments. Nature, 266(5604), 730–732. http://doi.org/10.1038/266730a0
  17. Strasser, B., Gostner, J. M., & Fuchs, D. (2016). Mood, food, and cognition: role of tryptophan and serotonin. Curr. Opin. Clin. Nutr. Metab. Care, 19(1), 55–61. http://doi.org/10.1097/MCO.0000000000000237
  18. Duman, R. S., Sanacora, G., & Krystal, J. H. (2019). Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron, 102(1), 75–90. http://doi.org/10.1016/j.neuron.2019.03.013
  19. Sanacora, G., Treccani, G., & Popoli, M. (2012). Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology, 62(1), 63–77. http://doi.org/10.1016/j.neuropharm.2011.07.036
  20. Zanos, P., & Gould, T. D. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801–811. http://doi.org/10.1038/mp.2017.255

Published

2026-03-31