Antidepressant-like effect of Entada Africana Guill. & Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress

Background: Entada Africana is used to treat various disease conditions including stomach ache, cataract, liver disease, epilepsy and depression. Previous research reported its antidepressant properties in acute depression models. However, its activity in chronic model and the associated signaling p...

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Main Authors: M.Y. Bebeji, A.H. Yaro, A.R. Abubakar, M.H. Ahmad, A.B. Nazifi, A.A.E. Ahmed
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Phytomedicine Plus
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667031325000818
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author M.Y. Bebeji
A.H. Yaro
A.R. Abubakar
M.H. Ahmad
A.B. Nazifi
A.A.E. Ahmed
author_facet M.Y. Bebeji
A.H. Yaro
A.R. Abubakar
M.H. Ahmad
A.B. Nazifi
A.A.E. Ahmed
author_sort M.Y. Bebeji
collection DOAJ
description Background: Entada Africana is used to treat various disease conditions including stomach ache, cataract, liver disease, epilepsy and depression. Previous research reported its antidepressant properties in acute depression models. However, its activity in chronic model and the associated signaling pathways remain unclear. Purpose: To elucidate the antidepressant-like effect of ethanol leaf extract of Entada Africana (EEEA) in chronic model of depression and the possible mechanism(s). Methods: Limit test was utilized in determining the oral median lethal dose (LD50). To establish the potential roles of monoamine neurotransmitters in the antidepressant action of EEEA, groups of mice were pre-administered prazosin (1 mg/kg), cyproheptadine (3 mg/kg), and haloperidol (0.2 mg/kg), 30 min before administering EEEA (4 mg/kg) or imipramine (10 mg/kg). In a separate experiment, animals were depressed via chronic unpredictable mild stress (CUMS), followed by sucrose preference, open field (OF), and tail suspension (TS) tests. The quantities of cortisol, brain-derived neurotrophic factor (BDNF), superoxide dismutase, and malondialdehyde were estimated. Phytochemical profiling of the extract was also conducted. Results: The oral LD50 was estimated to be >2000 mg/kg in mice. Pre-administration of prazosin, cyproheptadine, and haloperidol significantly (p < 0.05) attenuated the antidepressant action of EEEA. In CUMS experiment, EEEA remarkably (p < 0.05) reversed the weight loss, improved sucrose consumption, increased exploration in OF, and shortened the duration of motionlessness. EEEA significantly (p < 0.05) lowered the serum cortisol, increased BDNF concentration, and ameliorated oxidative stress. Flavonoids, saponins, terpenoids and tannins were identified. Conclusions: Entada Africana exerted antidepressant-like effect in chronic model of depression, which may be mediated via modifications of monoamine NTs, cortisol, BDNF, and oxidative stress pathways.
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spelling doaj-art-a0462ea6a29f4ae0b39113fc4904b20b2025-08-21T04:17:24ZengElsevierPhytomedicine Plus2667-03132025-08-015310080910.1016/j.phyplu.2025.100809Antidepressant-like effect of Entada Africana Guill. &amp; Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stressM.Y. Bebeji0A.H. Yaro1A.R. Abubakar2M.H. Ahmad3A.B. Nazifi4A.A.E. Ahmed5Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University Kano, 700233 Nigeria; Corresponding author.Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University Kano, 700233 NigeriaDepartment of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University Kano, 700233 NigeriaDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USADepartment of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University Kano, 700233 NigeriaDepartment of Pharmacology, Faculty of Medicine, Al Baha University, Al Baha 1988, Saudi ArabiaBackground: Entada Africana is used to treat various disease conditions including stomach ache, cataract, liver disease, epilepsy and depression. Previous research reported its antidepressant properties in acute depression models. However, its activity in chronic model and the associated signaling pathways remain unclear. Purpose: To elucidate the antidepressant-like effect of ethanol leaf extract of Entada Africana (EEEA) in chronic model of depression and the possible mechanism(s). Methods: Limit test was utilized in determining the oral median lethal dose (LD50). To establish the potential roles of monoamine neurotransmitters in the antidepressant action of EEEA, groups of mice were pre-administered prazosin (1 mg/kg), cyproheptadine (3 mg/kg), and haloperidol (0.2 mg/kg), 30 min before administering EEEA (4 mg/kg) or imipramine (10 mg/kg). In a separate experiment, animals were depressed via chronic unpredictable mild stress (CUMS), followed by sucrose preference, open field (OF), and tail suspension (TS) tests. The quantities of cortisol, brain-derived neurotrophic factor (BDNF), superoxide dismutase, and malondialdehyde were estimated. Phytochemical profiling of the extract was also conducted. Results: The oral LD50 was estimated to be >2000 mg/kg in mice. Pre-administration of prazosin, cyproheptadine, and haloperidol significantly (p < 0.05) attenuated the antidepressant action of EEEA. In CUMS experiment, EEEA remarkably (p < 0.05) reversed the weight loss, improved sucrose consumption, increased exploration in OF, and shortened the duration of motionlessness. EEEA significantly (p < 0.05) lowered the serum cortisol, increased BDNF concentration, and ameliorated oxidative stress. Flavonoids, saponins, terpenoids and tannins were identified. Conclusions: Entada Africana exerted antidepressant-like effect in chronic model of depression, which may be mediated via modifications of monoamine NTs, cortisol, BDNF, and oxidative stress pathways.http://www.sciencedirect.com/science/article/pii/S2667031325000818Entada AfricanaAntidepressantCUMSTSTPathways
spellingShingle M.Y. Bebeji
A.H. Yaro
A.R. Abubakar
M.H. Ahmad
A.B. Nazifi
A.A.E. Ahmed
Antidepressant-like effect of Entada Africana Guill. &amp; Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress
Phytomedicine Plus
Entada Africana
Antidepressant
CUMS
TST
Pathways
title Antidepressant-like effect of Entada Africana Guill. &amp; Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress
title_full Antidepressant-like effect of Entada Africana Guill. &amp; Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress
title_fullStr Antidepressant-like effect of Entada Africana Guill. &amp; Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress
title_full_unstemmed Antidepressant-like effect of Entada Africana Guill. &amp; Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress
title_short Antidepressant-like effect of Entada Africana Guill. &amp; Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress
title_sort antidepressant like effect of entada africana guill amp perr fabaceae in mice involvement of monoamine neurotransmitters cortisol bdnf and oxidative stress
topic Entada Africana
Antidepressant
CUMS
TST
Pathways
url http://www.sciencedirect.com/science/article/pii/S2667031325000818
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