Author(s):
Lakshmanan Ganesh, Deepa B, Shyamjith Manikkoth, Anuroopa G Nadh
Email(s):
bdeepa05@gmail.com , deepashyam@nitte.edu.in
DOI:
10.52711/0974-360X.2023.00585 
Address:
Lakshmanan Ganesh1, Deepa B2*, Shyamjith Manikkoth3, Anuroopa G Nadh4
1MBBS Student, KS Hegde Medical Academy, Mangalore, India
2Department of Pharmacology, KS Hegde Medical Academy, Mangalore, India
3Department of Pharmacology, Kanachur Institute of Medical Sciences, Mangalore, India
4Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram
*Corresponding Author
Published In:
Volume - 16,
Issue - 8,
Year - 2023
ABSTRACT:
Objective: To determine the anxiolytic activity of coconut water by pre-clinical studies. Materials and Methods: The anxiolytic activity of coconut water was screened by neuropharmacology and molecular docking studies. Twenty-four adult female rats of the Wistar strain were divided equally into four groups: Group I: Distilled water [3ml/Kg]; Group II: Coconut water [3ml/Kg]; Group III: Diazepam [5mg/Kg]; Group IV: Coconut water [3ml/Kg] + Diazepam [2.5mg/Kg]. All agents were administered orally for 15 days. Elevated plus maze and light/dark arena apparatus tests were used to assess anxiety in rats. Once the pharmacological screening was done, rats were sacrificed, and brains were removed out to estimate GABA levels. An insilico docking of bio-active components in coconut water was done to probe the possible mechanism of action. Results: This study showed coconut water produced significant anxiolytic activity in rats. Brain biochemical analysis revealed coconut water significantly increased GABA levels. Computational studies revealed that the phytocompound ‘Zeatin’ in coconut water could block gamma-aminobutyric acid transaminase, the enzyme responsible for GABA degradation, thereby increasing GABA levels. Conclusion: Coconut water has anxiolytic-like activity by modulating GABAergic neurotransmission.
Cite this article:
Lakshmanan Ganesh, Deepa B, Shyamjith Manikkoth, Anuroopa G Nadh. Anxiolytic activity of Coconut water by GABA Modulation as Evidenced by Pharmacological Experiments and Molecular Docking Studies. Research Journal of Pharmacy and Technology 2023; 16(8):3544-8. doi: 10.52711/0974-360X.2023.00585
Cite(Electronic):
Lakshmanan Ganesh, Deepa B, Shyamjith Manikkoth, Anuroopa G Nadh. Anxiolytic activity of Coconut water by GABA Modulation as Evidenced by Pharmacological Experiments and Molecular Docking Studies. Research Journal of Pharmacy and Technology 2023; 16(8):3544-8. doi: 10.52711/0974-360X.2023.00585 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-8-5
REFERENCES:
1. Craske MG, Rauch SL, Ursano R, Prenoveau J, Pine DS, Zinbarg RE. What Is an Anxiety Disorder? Depression and Anxiety, 2009; 26: 1066–85.doi: 10.1002/da.20633.
2. Aswini A, Tarun K, Ajay M, Anil H. Anxiety disorders: A review. International Research Journal of Pharmacy, 2011; 2(5):18-23.
3. Kjernisted KD, Bleau P. Long-term goals in the management of acute and chronic anxiety disorders. Can J Psychiatry, 2004; 49(3): 51-63.PMID: 15147036
4. Pollack MH. Unmet needs in the treatment of anxiety disorders. Psychopharmacol Bull, 2004; 38(1): 31-37. PMID: 15278016
5. Agbafor KN, Elom SO, Ogbanshi ME, Oko AO, Uraku AJ, Nwankwo VUO, Aleand KBA, Obiudu I. Antioxidant property and cardiovascular effects of coconut (Cocos nucifera) water. International Journal of Biochemistry Research and Review, 2015;5(4): 259-63.
6. Offor CE, Adetarami O, Wali BUN, Igwenyi IO, Afiukwa CA. Effect of Cocos nucifera water on liver enzymes. Middle-East Journal of Scientific Research, 2014; 21 (5): 844-47. DOI: 10.5829/idosi.mejsr.2014.21.05.8496
7. Santos JLA, Bispo VS, Filho ABC, Pinto IFD, Dantas LS, Vasconcelos DF, et al. Evaluation of chemical constituents and antioxidant activity of coconut water (Cocus nucifera L.) and caffeic acid in cell culture. An Acad Bras Cienc, 2013; 85 (4): 1235-47.doi: 10.1590/0001-37652013105312
8. Yong JWH, Ge L, Ng YF, Tan SN. The chemical composition and biological properties of coconut (Cocos nucifera L.) Water. Molecules, 2009; 14 (12):5144-64.
9. Johnkennedy N, Ndubueze EH, Augustine I, Chioma D, Okey EC. Coconut water consumption and its effect on sex hormone concentrations. JKIMSU, 2014;3(2): 107-10.
10. Griebel G, Perrault G, Sanger DJ. Characterization of the behavioral profile of the non-peptide CRF receptor antagonist CP-154,526 in anxiety models in rodents. Comparison with Diazepam and buspirone. Psychopharmacology, 1998;138(1):55-66.doi: 10.1007/s002130050645
11. Manikkoth S, Chandrasekhar R, Rao SN. Antianxiety effect of ethanolic extract of leaves of Tylophora indica in Wistar albino rats. IJRAP. 2013; 4(1):127-29.
12. Gururaja MP, Nidhi P Shetty, Himanshu Joshi. Attenuation of Experimentally Induced Anxiety by Panchagavya Ghrita in Mice. Research Journal of Pharmacy and Technology. 2022; 15(11):4897-0. doi: 10.52711/0974-360X.2022.00822
13. Habibur Rahman, Eswaraiah MC. Simple spectroscopic Methods for estimating Brain Neurotransmitters, Antioxidant Enzymes of Laboratory animals like Mice: A review 2017 Available in http://www.pharmatutor.org/articles/simple-spectroscopicmethod-estimating-brain-neurotransmitter-antioxidnat-enzymes-lab-animals
14. Uni Prot Consortium. Uni Prot: a worldwide hub of protein knowledge. Nucleic acids research, 2019; 47(D1): D506-D515.https://doi.org/10.1093/nar/gky1049
15. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res, 2018; 46(W1): W296-303.doi: 10.1093/nar/gky427.
16. Laskowski RA, MacArthur MW, Moss DS, and Thornton JM. PROCHECK: A program to check the stereochemical quality of protein structures. Journal of applied crystallography, 1993; 26(2): 283-91.https://doi.org/10.1107/S0021889892009944
17. Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A and Wang J. PubChem substance and compound databases. Nucleic acids research, 2016; 44(D1): D1202- D1213.https://doi.org/10.1093/nar/gkv951
18. Lipinski CA, Lombardo F, Dominy BW, and Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev,1997; 23: 3-25. DOI: 10.1016/s0169-409x(00)00129-0
19. Hodgson J. ADMET—turning chemicals into drugs. Nature Biotech,2001;19: 722-6. DOI: 10.1038/90761
20. Tan SN, Yong JWH, and Ge L. Analyses of phytohormones in coconut (Cocos Nucifera L.) water using capillary electrophoresis-tandem mass spectrometry. Chromatography, 2014; 1(4): 211-26. https://doi.org/10.3390/chromatography1040211
21. Storici P, Capitani G, De Biase D, Moser M, John R. A., Jansonius, JN, Schirmer T. Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy. Biochemistry, 1999; 38(27): 8628-34. DOI: 10.1021/bi990478j
22. Hou R, Baldwin DS. A neuroimmunological perspective on anxiety disorders. Hum. Psychopharmacol.2012; 27: 6–14. DOI: 10.1002/hup.1259
23. Moons WG, Shields GS. Anxiety, not anger, induces inflammatory activity: an avoidance/approach model of immune system activation. Emotion, 2015; 15(4), 463–76. DOI: 10.1037/emo0000055
24. Munhoz CD, García-Bueno B, Madrigal JLM, Lepsch LB, Scavone C, Leza JC. Stress-induced neuroinflammation mechanisms and new pharmacological targets. Brazilian Journal of Medical and Biological Research, 2008; 41: 1037-46. DOI: 10.1590/s0100-879x2008001200001
25. Dugan LL, Ali SS, Shekhtman G, Roberts AJ, Lucero J, et al. IL-6 mediated degeneration of forebrain GABAergic interneurons and cognitive impairment in aged mice through activation of neuronal NADPH Oxidase. PLoSONE, 2009; 4(5):e5518:1-13 doi:10.1371/journal.pone. 0005518.
26. Khalifeh S, Oryan S, Digaleh H, Shaerzadeh F, Khodagholi F, Maghsoudi N, et al. Involvement of Nrf2 in development of anxiety-like behavior by linking Bcl2 to oxidative phosphorylation: Estimation in Rat hippocampus, amygdala, and prefrontal cortex. J Mol Neurosci, 2015; 55:492–99. DOI: 10.1007/s12031-014-0370-z
27. Silverman MN, Macdougall MG, Hu F, Pace TWW, Raison CL, Miller AH. Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behaviour in virally infected mice. Mol Psychiatry. 2007; 12(4): 408–17.doi: 10.1038/sj.mp.4001921
28. Mendez-David I, Tritschler L, AliZE, Damiens MH, Pallardy M, David DJ, Kerdine-Römer S, Gardier AM. Nrf2-signaling and BDNF: A new target for the antidepressant-like activity of chronic flu. Neuroscience Letters, 2015; 597:121–26. DOI: 10.1016/j.neulet.2015.04.036
29. Cristo´va˜o-Ferreira S, Vaz S, Ribeiro J, Sebastião AM. Adenosine A2A receptors enhance GABA transport into nerve terminals by restraining PKC inhibition of GAT-1. J. Neurochem, 2009; 109: 336–47. DOI: 10.1111/j.1471-4159.2009.05963.x
30. Krishnendu M, Amitava K, Dipesh KD, Swaraj BK, Ujjal Das, Sayan G. Protective effect of coconut water concentrate and its active component shikimic acid against hydroperoxide mediated oxidative stress through suppression of NFκB and activation of Nrf2 pathway. Journal of Ethnopharmacology, 2004; 155:132–46. DOI: 10.1016/j.jep.2014.04.046
31. Lima EBC, Sousa CNS, Meneses LN, Ximenes NC, Santos Júnior MA, Vasconcelos GS, et al. Cocos nucifera (L.) (Arecaceae): A phytochemical and pharmacological review. Brazilian Journal of Medical and Biological Research, 2015; 48(11): 953–64. doi: 10.1590/1414-431X20154773
32. Lappas CM. The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A2A receptor activation. Cellular and Molecular Immunology, 2015; 12: 107–12. https://doi.org/10.1038/cmi.2014.33
33. Mi JK, Soo JC, Seung-Taik L, Hye KK, Young JK, Ho-Geun Y, Dong-Hoon S. Zeatin supplement improves scopolamine induced memory impairment in mice. Bioscience, Biotechnology, and Biochemistry 2008, 72:2, 577-81,DOI: 10.1271/bbb.70480