Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways

doi:10.1007/s13659-023-00399-8

Natural Products and Bioprospecting ›› 2023, Vol. 13 ›› Issue (5): 33-33.DOI: 10.1007/s13659-023-00399-8

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Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways

Donatus Wewura Adongo¹, Charles Kwaku Benneh¹, Augustine Tandoh¹, Robert Peter Biney², Kennedy Kwami Edem Kukuia³, Priscilla Kolibea Mante⁴, Benjamin Kingsley Harley⁵, David Oteng¹, Emmanuel Aduboffour Appiah¹, Ernest Cudjoe Anorbor¹, Eric Woode¹

1. Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana;
2. Department of Pharmacotherapeutics and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of Cape Coast, Cape Coast, Ghana;
3. Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana;
4. Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;
5. Department of Pharmacognosy and Herbal Medicine, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana

Received:2023-07-11 Online:2023-11-03 Published:2023-10-24
Contact: Donatus Wewura Adongo,E-mail:dadongo@uhas.edu.gh
Supported by:
We appreciate the technical support provided by Messrs. R. Agbolosoo and B. Cato of the Department of Pharmacology and Toxicology at the University of Health and Allied Sciences (UHAS).

Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways

1. Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana;
2. Department of Pharmacotherapeutics and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of Cape Coast, Cape Coast, Ghana;
3. Department of Medical Pharmacology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana;
4. Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;
5. Department of Pharmacognosy and Herbal Medicine, School of Pharmacy, University of Health and Allied Sciences, Ho, Ghana

通讯作者: Donatus Wewura Adongo,E-mail:dadongo@uhas.edu.gh
基金资助:
We appreciate the technical support provided by Messrs. R. Agbolosoo and B. Cato of the Department of Pharmacology and Toxicology at the University of Health and Allied Sciences (UHAS).

Abstract

Abstract: Pseudospondias microcarpa is used in ethnomedicine to manage central nervous system diseases. The hydroethanolic extract (PME) from the leaves of the plant has shown anxiolytic-like properties in mice anxiety models. However, its effects in chronic anxiety models and possible mechanism(s) of action were not studied. Therefore, the current study evaluated the anxiolytic-like mechanisms of PME in zebrafish models of anxiety. The zebrafish light dark test (LDT) and novel tank test (NTT) were employed to assess the anxiolytic-like effects of PME (0.1, 0.3, 1.0 mg mL^-1), fluoxetine (3×10^-5 mg mL^-1) and diazepam (1.5×10^-7 mg mL^-1). The chronic unpredictable stress (CUS) test was used to further evaluate the extract’s anxiolytic-like properties. The potential mechanisms of anxiolytic action of the extract was evaluated after pre-treated with flumazenil, granisetron, methysergide, or pizotifen, all at 1×10^-3 mg mL^-1. The extract significantly decreased anxiety behaviours in the NT and LD tests. These observed effects of the extract were however counteracted by flumazenil, granisetron, methysergide and pizotifen pre-treatment. In addition, PME treatment significantly reversed CUS-induced anxiety behaviours in zebrafish. Results show that PME possesses anxiolytic-like effects possibly through interaction with serotonergic and gamma-aminobutyric acid mediated pathways.

Key words: Anxiety disorders, Pseudospondias microcarpa, Zebrafish, Novel tank, Benzodiazepines

摘要： Pseudospondias microcarpa is used in ethnomedicine to manage central nervous system diseases. The hydroethanolic extract (PME) from the leaves of the plant has shown anxiolytic-like properties in mice anxiety models. However, its effects in chronic anxiety models and possible mechanism(s) of action were not studied. Therefore, the current study evaluated the anxiolytic-like mechanisms of PME in zebrafish models of anxiety. The zebrafish light dark test (LDT) and novel tank test (NTT) were employed to assess the anxiolytic-like effects of PME (0.1, 0.3, 1.0 mg mL^-1), fluoxetine (3×10^-5 mg mL^-1) and diazepam (1.5×10^-7 mg mL^-1). The chronic unpredictable stress (CUS) test was used to further evaluate the extract’s anxiolytic-like properties. The potential mechanisms of anxiolytic action of the extract was evaluated after pre-treated with flumazenil, granisetron, methysergide, or pizotifen, all at 1×10^-3 mg mL^-1. The extract significantly decreased anxiety behaviours in the NT and LD tests. These observed effects of the extract were however counteracted by flumazenil, granisetron, methysergide and pizotifen pre-treatment. In addition, PME treatment significantly reversed CUS-induced anxiety behaviours in zebrafish. Results show that PME possesses anxiolytic-like effects possibly through interaction with serotonergic and gamma-aminobutyric acid mediated pathways.

关键词: Anxiety disorders, Pseudospondias microcarpa, Zebrafish, Novel tank, Benzodiazepines

Donatus Wewura Adongo, Charles Kwaku Benneh, Augustine Tandoh, Robert Peter Biney, Kennedy Kwami Edem Kukuia, Priscilla Kolibea Mante, Benjamin Kingsley Harley, David Oteng, Emmanuel Aduboffour Appiah, Ernest Cudjoe Anorbor, Eric Woode. Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways[J]. Natural Products and Bioprospecting, 2023, 13(5): 33-33.

References

[1] Steimer T. Animal models of anxiety disorders in rats and mice: some conceptual issues. Dialogues Clin Neurosci. 2011;13(4):495-506.
[2] Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues Clin Neurosci. 2017;19(2):93-107.
[3] Ravindran LN, Stein MB. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry. 2010;71(7):839-54.
[4] Graf H, Walter M, Metzger CD, Abler B. Antidepressant-related sexual dysfunction—perspectives from neuroimaging. Pharmacol Biochem Behav. 2014;121:138-45.
[5] Biney RP, Benneh CK, Kyekyeku JO, Ameyaw EO, Boakye-Gyasi E, Woode E. Attenuation of anxiety behaviours by xylopic acid in mice and zebrafish models of anxiety disorder. Pharm Biosci J. 2018. https://doi.org/10.20510/ukjpb/6/i3/173546.
[6] Santarsieri D, Schwartz TL. Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs Context. 2015;4:1-12.
[7] Griebel G, Holmes A. 50 years of hurdles and hope in anxiolytic drug discovery. Nat Rev Drug Discov. 2013;12(9):667-87.
[8] Khan A, Akram M, Thiruvengadam M, Daniyal M, Zakki SA, Munir N, et al. Anti-anxiety properties of selected medicinal plants. Curr Pharm Biotechnol. 2022;23(8):1041-60.
[9] Burkill HM. The useful plants of West Tropical Africa. Vol 1: families A-D. 2nd ed. Royal Botanic Gardens, Kew; 1985.
[10] Adongo DW, Mante PK, Edem Kukuia KK, Ameyaw EO, Woode E, Azi IH. Anxiolytic-like effect of the leaves of Pseudospondias microcarpa (A. Rich.) Engl. in mice. J Basic Clin Physiol Pharmacol. 2016;27(5):533-46.
[11] Adongo DW, Kukuia KKE, Mante PK, Ameyaw EO, Woode E. Antidepressant-like effect of the leaves of Pseudospondias microcarpa in mice: evidence for the involvement of the serotoninergic system, NMDA receptor complex, and nitric oxide pathway. BioMed Res Int. 2015. https://doi.org/10.1155/2015/397943.
[12] Adongo DW, Mante PK, Kukuia KKE, Woode E. Preclinical evidence of a rapid-onset antidepressant-like effect of Pseudospondias microcarpa hydroethanolic leaf extract in a chronic depression model. In: Proceedings of the Woode E Preclinical evidence of a rapid-onset antidepressant-like effect of Pseudospondias microcarpa hydroethanolic leaf extract in a chronic depression model International Journal of Basic Clinical Pharmacology, vol. 5. 2016. p. 1254-62.
[13] Adongo DW, Mante PK, Kukuia KKE, Benneh CK, Biney RP, Boakye-Gyasi E, et al. Fast-onset effects of Pseudospondias microcarpa (A. Rich) Engl. (Anacardiaceae) hydroethanolic leaf extract on behavioral alterations induced by chronic mild stress in mice. PLoS ONE. 2023;18(2):e0278231.
[14] Cryan JF, Holmes A. The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov. 2005;4(9):775-90.
[15] Kalueff AV, Echevarria DJ, Stewart AM. Gaining translational momentum: more zebrafish models for neuroscience research. Amsterdam: Elsevier; 2014. p. 1-6.
[16] Kalueff AV, Stewart AM, Gerlai R. Zebrafish as an emerging model for studying complex brain disorders. Trends Pharmacol Sci. 2014;35(2):63-75.
[17] Stewart AM, Ullmann JF, Norton WH, Parker M, Brennan C, Gerlai R, et al. Molecular psychiatry of zebrafish. Mol Psychiatry. 2015;20(1):2-17.
[18] Khan KM, Collier AD, Meshalkina DA, Kysil EV, Khatsko SL, Kolesnikova T, et al. Zebrafish models in neuropsychopharmacology and CNS drug discovery. Br J Pharmacol. 2017;174(13):1925-44.
[19] 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.
[20] Cueto-Escobedo J, German-Ponciano LJ, Guillén-Ruiz G, Soria-Fregozo C, Herrera-Huerta EV. Zebrafish as a useful tool in the research of natural products with potential anxiolytic effects. Front Behav Neurosci. 2022;15:356.
[21] Cianca V, Bartolini T, Porfiri M, Macrì S. A robotics-based behavioral paradigm to measure anxiety-related responses in zebrafish. PLoS ONE. 2013;8(7):e69661.
[22] Egan RJ, Bergner CL, Hart PC, Cachat JM, Canavello PR, Elegante MF, et al. Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish. Behav Brain Res. 2009;205(1):38-44.
[23] Stewart A, Gaikwad S, Kyzar E, Green J, Roth A, Kalueff AV. Modeling anxiety using adult zebrafish: a conceptual review. Neuropharmacology. 2012;62(1):135-43.
[24] Stewart A, Wu N, Cachat J, Hart P, Gaikwad S, Wong K, et al. Pharmacological modulation of anxiety-like phenotypes in adult zebrafish behavioral models. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(6):1421-31.
[25] Bencan Z, Sledge D, Levin ED. Buspirone, chlordiazepoxide and diazepam effects in a zebrafish model of anxiety. Pharmacol Biochem Behav. 2009;94(1):75-80.
[26] Benneh CK, Biney RP, Mante PK, Tandoh A, Adongo DW, Woode E. Maerua angolensis stem bark extract reverses anxiety and related behaviours in zebrafish—involvement of GABAergic and 5-HT systems. J Ethnopharmacol. 2017;207:129-45.
[27] Maximino C, da Silva AWB, Gouveia A Jr, Herculano AM. Pharmacological analysis of zebrafish (Danio rerio) scototaxis. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(2):624-31.
[28] 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(1):70-86.
[29] Magno LDP, Fontes A, Gonçalves BMN, Gouveia A. Pharmacological study of the light/dark preference test in zebrafish (Danio rerio): waterborne administration. Pharmacol Biochem Behav. 2015;135:169-76.
[30] Chakravarty S, Reddy BR, Sudhakar SR, Saxena S, Das T, Meghah V, et al. Chronic unpredictable stress (CUS)-induced anxiety and related mood disorders in a zebrafish model: altered brain proteome profile implicates mitochondrial dysfunction. PLoS ONE. 2013;8(5):e63302.
[31] Piato ÂL, Capiotti KM, Tamborski AR, Oses JP, Barcellos LJ, Bogo MR, et al. Unpredictable chronic stress model in zebrafish (Danio rerio): behavioral and physiological responses. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(2):561-7.
[32] Abdul Rahim N, Nordin N, Ahmad Rasedi NIS, Mohd Kauli FS, Wan Ibrahim WN, Zakaria F. Behavioral and cortisol analysis of the anti-stress effect of Polygonum minus (Huds) extracts in chronic unpredictable stress (CUS) zebrafish model. Comp Biochem Physiol C. 2022;256:109303.
[33] Wu J, Yan B, Bao M, Shen J, Zheng P, Wu D, et al. Early life exposure to chronic unpredictable stress induces anxiety-like behaviors and increases the excitability of cerebellar neurons in zebrafish. Behav Brain Res. 2023;437:114160.
[34] Biney RP, Benneh CK, Adongo DW, Ameyaw EO, Woode E. Evidence of an antidepressant-like effect of xylopic acid mediated by serotonergic mechanisms. Psychopharmacology. 2021;238(8):2105-20.
[35] Zwanzger P, Eser D, Nothdurfter C, Baghai T, Möller H-J, Padberg F, et al. Effects of the GABA-reuptake inhibitor tiagabine on panic and anxiety in patients with panic disorder. Pharmacopsychiatry. 2009;42(06):266-9.
[36] Gilhotra N, Dhingra D. GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice. Brain Res. 2010;1352:167-75.
[37] Kim Y-J, Nam R-H, Yoo YM, Lee C-J. Identification and functional evidence of GABAergic neurons in parts of the brain of adult zebrafish (Danio rerio). Neurosci Lett. 2004;355(1-2):29-32.
[38] Mussulini BHM, Leite CE, Zenki KC, Moro L, Baggio S, Rico EP, et al. Seizures induced by pentylenetetrazole in the adult zebrafish: a detailed behavioral characterization. PLoS ONE. 2013;8(1):e54515.
[39] Çiçek SS. Structure-dependent activity of natural GABA (A) receptor modulators. Molecules. 2018;23(7):1512.
[40] Mendes Hacke AC, Miyoshi E, Marques JA, Pereira RP. Anxiolytic properties of Cymbopogon citratus (DC.) stapf extract, essential oil and its constituents in zebrafish (Danio rerio). J Ethnopharmacol. 2020;260:113036.
[41] Adongo DW, Mante PK, Kukuia KKE, Biney RP, Boakye-Gyasi E, Benneh CK, et al. Anticonvulsant activity of Pseudospondias microcarpa (A. Rich) Engl. hydroethanolic leaf extract in mice: the role of excitatory/inhibitory neurotransmission and nitric oxide pathway. J Ethnopharmacol. 2017;206:78-91.
[42] Maximino C. Nodal structures in anxiety-like and panic-like responses. In: Serotonin and Anxiety. Springer Briefs in Neuroscience. New York, NY: Springer; 2012. pp. 37-78.

Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways

Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways

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