Assessment of Anxiolytic Activity of Brahmi (Bacopa monnieri) in Zebrafish Model System

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Authors

  • Padmshree Mudgal
     Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007 ,IN
  • Radhika Gupta
     Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007 ,IN
  • Adita Joshi
     Sansriti Foundation, Delhi - 110016 ,IN
  • Chandhana Prakash
     Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007 ,IN
  • Kajal Gupta
     Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007 ,IN
  • Ritika Sachdeva
     Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007 ,IN
  • Niharika Joshi
     Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007 ,IN

DOI:

https://doi.org/10.18311/jnr/2023/31362

Keywords:

Cortisol, HPI Axis, Scototaxis, Stress, Thigmotaxis

Abstract

The increasing prevalence of anxiety and stress-related disorders has made it a leading contributor to the global health burden. The present treatment options have severe side effects and show remission on discontinuation of the medication. Hence, there is an urgent need to explore safer alternative treatments for long-term usage with minimum toxicity. The medicinal plant Brahmi (Bacopa monnieri) has been used in Indian traditional medicine as a neural tonic for centuries. The present study aimed to study the toxicity and anxiolytic activity of Brahmi using the zebrafish model system. The toxicity assays determined the minimum effective concentration of Brahmi to be 0.01%. In addition, behavioral assays such as thigmotaxis and scototaxis and endocrine assays such as the measurement of cortisol levels in stressed zebrafish larvae were performed. Zebrafish embryos exposed to 0.2% Brahmi up to seven days post fertilization (dpf) did not show any developmental toxicity. Behavioral and endocrine assays were performed on 5dpf zebrafish larvae treated with 0.01% Brahmi extract. Our studies show that Brahmi significantly reduced thigmotaxis (wall hugging) and scototaxis behavior in zebrafish larvae exposed to osmotic stress as compared to untreated stressed larvae. Stress activates the hypothalamic-pituitary-interrenal axis and stimulates the release of cortisol in zebrafish larvae. Whole body cortisol assay has shown that Brahmi significantly reduced the stress-induced release of cortisol in zebrafish larvae. Our studies report that Brahmi mitigates the stress response in zebrafish larvae and has minimum toxicity. This suggests that Brahmi may be a safe option for long term management of stress.

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Author Biographies

Padmshree Mudgal, Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007

Professor,

Department of Biochemistry

Daulat Ram College,

University of Delhi

Delhi

Radhika Gupta, Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007

Associate Professor,

Department of Biochemistry

Daulat Ram College,

University of Delhi

Delhi

Adita Joshi, Sansriti Foundation, Delhi - 110016

Director

Sansriti foundation, Delhi

Chandhana Prakash, Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007

Undergraduate Student ,

Department of Biochemistry

Daulat Ram College,

University of Delhi

Delhi

Kajal Gupta, Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007

Undergraduate Student, 

Biochemistry Department, Daulat Ram College, University of Delhi, Delhi

Ritika Sachdeva, Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007

Undergraduate student, 

Department of Biochemistry

Daulat Ram College,

University of Delhi

Delhi

Niharika Joshi, Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi - 110007

Undergraduate Student,

Department of Biochemistry, Daulat Ram College, University of Delhi, Delhi

 

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Published

2023-06-13

How to Cite

Mudgal, P., Gupta, R., Joshi, A., Prakash, C., Gupta, K., Sachdeva, R., & Joshi, N. (2023). Assessment of Anxiolytic Activity of Brahmi (<i>Bacopa monnieri</i>) in Zebrafish Model System. Journal of Natural Remedies, 23(2), 661–670. https://doi.org/10.18311/jnr/2023/31362

Issue

Volume 23, Issue 2, April 2023

Section

Short Communication

License

Copyright (c) 2023 Padmshree Mudgal, Radhika Gupta, Adita Joshi, Chandhana Prakash, Kajal Gupta, Ritika Sachdeva, Niharika Joshi (Author)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Crossref
Scopus
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Europe PMC
Received 2022-10-08
Accepted 2023-05-02
Published 2023-06-13

 

References

Collaborators C-MD. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021; 398(10312):1700-12. https://doi.org/10.1016/S0140-6736(21)02143-7 DOI: https://doi.org/10.1016/S0140-6736(21)02143-7

WHO. COVID-19 pandemic triggers 25% increase in prevalence of anxiety and depression worldwide. 2022 [Available from: https://www.who.int/news/item/02-03-2022-covid-19-pandemic-triggers-25-increase-in-prevalence-of-anxiety-and-depression-worldwide]

Rogers AH, Wieman ST, Baker AT. Anxiety comorbidities: Mood disorders, substance disorders, and chronic mental illness. Bui E, Charney ME, Baker AW, editors: Humana / Springer Nature; 2020; 77-103. https://doi.org/10.1007/978-3-030-30687-8_5 DOI: https://doi.org/10.1007/978-3-030-30687-8_5

Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues Clin Neurosci. 2017; 19(2):93-107. https://doi.org/10.31887/DCNS.2017.19.2/bbandelow DOI: https://doi.org/10.31887/DCNS.2017.19.2/bbandelow

Garakani A, Murrough JW, Freire RC, Thom RP, Larkin K, Buono FD, et al. Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Front Psychiatry. 2020. https://doi.org/10.3389/fpsyt.2020.595584 DOI: https://doi.org/10.3389/fpsyt.2020.595584

Lader M. Long-term anxiolytic therapy: the issue of drug withdrawal. J Clin Psychiatry. 1987; 48:12-6. PMID: 2891684.

Medicines CoSo. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and reuptake inhibitors (SNRIs): use and safety. Medicines and Healthcare products Regulatory Agency (MHRA). 2014. [Available at: https://www.gov.uk/government/publications/ssris-and-snris-use-and-safety/selective-serotonin-reuptake-inhibitors-ssris-and-serotonin-and-noradrenaline-reuptake inhibitors-snris-use and-safety].

George TT, Tripp J. Alprazolam: StatPearls Publishing. 2022. [Available from: https://www.ncbi.nlm.nih.gov/books/NBK538165/].

Parsaik AK, Mascarenhas SS, Khosh-Chashm D, Hashmi A, John V, Okusaga O, et al. Mortality associated with anxiolytic and hypnotic drugs-A systematic review and meta-analysis. Aust N Z J Psychiatry. 2016; 50(6):520-33. https://doi.org/10.1177/0004867415616695 DOI: https://doi.org/10.1177/0004867415616695

Ezzat SM, Jeevanandam J, Egbuna C, Kumar S, Ifemeje JC. Phytochemistry: An in-silico and in-vitro Update. Kumar S, Egbuna C, editors. 2019. Phytochemistry: An in-silico and in-vitro Update. Springer, Singapore. https://doi.org/10.1007/978-981-13-6920-9_1 DOI: https://doi.org/10.1007/978-981-13-6920-9_1

Basu N, Rastogi R, Dhar ML. Chemical examination of Bacopa mienniera wettst: part III-bacoside B. Ind J Chem. 1967; 5:84-95.

Bhattacharya SK, Ghosal S. Anxiolytic activity of a standardized extract of Bacopa monniera: an experimental study. Phytomedicine. 1998; 5:77-82. https://doi.org/10.1016/S0944-7113(98)80001-9 DOI: https://doi.org/10.1016/S0944-7113(98)80001-9

Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC. Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res. 2002; 16(7):639-45. https://doi.org/10.1002/ptr.1023 DOI: https://doi.org/10.1002/ptr.1023

Mannan M. Anxiolytic Effects of the Methanolic Extract of Bacopa monniera in Mice. Pharmacol. Pharm. 2019; 10:298-308. https://doi.org/10.4236/pp.2019.106024 DOI: https://doi.org/10.4236/pp.2019.106024

Singh HK, Shanker G, Patnaik GK. Neuropharmacological and anti-stress effects of bacosides: A memory enhancer. Ind J Pharmacol. 1996; 28:47

Sheikh N, Ahmad A, Siripurapu KB, Kuchibhotla VK, Singh S, Palit G. Effect of Bacopa monniera on stress-induced changes in plasma corticosterone and brain monoamines in rats. J Ethnopharmacol. 2007; 111(3):671-6. https://doi.org/10.1016/j.jep.2007.01.025 DOI: https://doi.org/10.1016/j.jep.2007.01.025

Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature. 2013; 496(7446):498-503. https://doi.org/10.1038/nature12111 DOI: https://doi.org/10.1038/nature12111

OECD guidelines for the testing of chemicals, Fish Embryo Acute Toxicity (FET) Test. OECD. 2013. https://doi.org/10.1787/9789264203709-en DOI: https://doi.org/10.1787/9789264203709-en

Stewart AM, Braubach O, Spitsbergen J, Gerlai R, Kalueff AV. Zebrafish models for translational neuroscience research: from tank to bedside. Trends Neurosci. 2014; 37(5):264-78. https://doi.org/10.1016/j.tins.2014.02.011 DOI: https://doi.org/10.1016/j.tins.2014.02.011

Kalueff AV, Gebhardt M, Stewart AM, Cachat JM, Brimmer M, Chawla JS, et al. Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond. Zebrafish. 2013; 10:70-86. https://doi.org/10.1089/zeb.2012.0861 DOI: https://doi.org/10.1089/zeb.2012.0861

McCarty R. Learning about stress: neural, endocrine and behavioral adaptations. Stress. 2016; 19(5):449-75. https://doi.org/10.1080/10253890.2016.1192120 DOI: https://doi.org/10.1080/10253890.2016.1192120

Demin KA, Taranov AS, Ilyin NP, Lakstygal AM, Volgin AD, de Abreu MS, et al. Understanding neurobehavioral effects of acute and chronic stress in zebrafish. Stress. 2021; 24(1):1-18. https://doi.org/10.1080/10253890.2020.17249 48 DOI: https://doi.org/10.1080/10253890.2020.1724948

de Abreu MS, Demin KA, Giacomini A, Amstislavskaya TG, Strekalova T, Maslov GO, et al. Understanding how stress responses and stress-related behaviors have evolved in zebrafish and mammals. Neurobiol Stress. 2021; 15:100405. https://doi.org/10.1016/j.ynstr.2021.100405 DOI: https://doi.org/10.1016/j.ynstr.2021.100405

Gupta R, Ranjan S, Yadav A, Verma B, Malhotra K, Madan M, et al. Toxic Effects of Food Colorants Erythrosine and Tartrazine on Zebrafish Embryo Development. Curr Res Nutr Food Sci. 2019; 7(3). https://doi.org/10.12944/CRNFSJ.7.3.26 DOI: https://doi.org/10.12944/CRNFSJ.7.3.26

Schnorr SJ, Steenbergen PJ, Richardson MK, Champagne DL. Measuring thigmotaxis in larval zebrafish. Behav Brain Res. 2012; 228(2):367-74. https://doi.org/10.1016/j.bbr.2011.12.016 DOI: https://doi.org/10.1016/j.bbr.2011.12.016

Clark KJ, Boczek NJ, Ekker SC. Stressing zebrafish for behavioral genetics. Rev Neurosci. 2011; 22(1):49-62. https://doi.org/10.1515/rns.2011.007 DOI: https://doi.org/10.1515/rns.2011.007

Bai Y, Liu H, Huang B, et al. Identification of environmental stressors and validation of light preference as a measure of anxiety in larval zebrafish. BMC Neurosci. 2016; 17(63). https://doi.org/10.1186/s12868-016-0298-z DOI: https://doi.org/10.1186/s12868-016-0298-z

Yeh CM, Glock M, Ryu S. An optimized whole-body cortisol quantification method for assessing stress levels in larval zebrafish. PLoS One. 2013; 8(11):e79406. https://doi.org/10.1371/journal.pone.0079406 DOI: https://doi.org/10.1371/journal.pone.0079406

Brimson JM, Brimson S, Prasanth MI, Thitilertdecha P, Malar DS, Tencomnao T. The effectiveness of Bacopa monnieri (Linn.) Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data. Sci Rep. 2021; 11(1):596. https://doi.org/10.1038/s41598-020-80045-2 DOI: https://doi.org/10.1038/s41598-020-80045-2

Sireeratawong S, Jaijoy K, Khonsung P, Lertprasertsuk N, Ingkaninan K. Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats. BMC Complement Altern Med. 2016; 16:249. https://doi.org/10.1186/s12906-016-1236-4 DOI: https://doi.org/10.1186/s12906-016-1236-4

Singh HK, Dhawan BN. Neuropsychopharmacological effects of the Ayurvedic Bacopa monniera Linn. (Brahmi) Indian J Pharmacol. 1997; 29:359-65. https://doi.org/10.1089/rej.2013.1431. DOI: https://doi.org/10.1089/rej.2013.1431

Nathan PJ, Clarke J, Lloyd J, Hutchison CW, Downey L, Stough C. The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects. Hum Psychopharmacol. 2001; 16(4):345-51. https://doi.org/10.1002/hup.306 DOI: https://doi.org/10.1002/hup.306

Basnet RM, Zizioli D, Taweedet S, Finazzi D, Memo M. Zebrafish Larvae as a Behavioral Model in Neuropharmacology. Biomedicines. 2019; 7(1). https://doi.org/10.3390/biomedicines7010023 DOI: https://doi.org/10.3390/biomedicines7010023

Wendelaar Bonga SE. The stress response in fish. Physiol Rev. 1997; 77(3):591-625. https://doi.org/10.1152/phys-rev.1997.77.3.59 DOI: https://doi.org/10.1152/physrev.1997.77.3.591