Antidepressant potential of Musa species peel extract in a rat model through modulation of oxidative stress, neurotransmitters, and CREB signaling pathway

Randa Samir HANNA; Khaled M.A. RAMADAN; Nareman S. ESHAK; Martha Emil ADLY; Sallah A. AL-HASHEDI; Hossam S. EL-BELTAGI; Jomanah Adil ALHUSSAIN; Mohamed A.A. MAHMOUD; Eslam S.A. BENDARY

doi:10.55779/nsb18112860

Authors

Randa Samir HANNA Assiut University, Faculty of Medicine, Biochemistry and Molecular Biology Department, Assiut (EG)
Khaled M.A. RAMADAN King Faisal University, Central Laboratories, Al-Ahsa 31982 (SA) https://orcid.org/0000-0003-0595-5394
Nareman S. ESHAK Assiut University, Faculty of Specific Education, Home Economics Department, Assiut (EG)
Martha Emil ADLY Assiut University, Faculty of Medicine, Department of Anatomy, Assiut (EG)
Sallah A. AL-HASHEDI King Faisal University, Central Laboratories, Al-Ahsa 31982 (SA) https://orcid.org/0000-0002-3183-9162
Hossam S. EL-BELTAGI King Faisal University, College of Agricultural and Food Sciences, Agricultural Biotechnology Department, Al-Ahsa 31982 (SA) https://orcid.org/0000-0003-4433-2034
Jomanah Adil ALHUSSAIN Abdulmonem Al-Rashed Humanitarian Foundation, Fab Lab, Al-Ahsa (SA)
Mohamed A.A. MAHMOUD Ain Shams University, Faculty of Agriculture, Department of Agricultural Biochemistry, P.O. Box 68, Hadayek Shobra, Cairo 11241 (EG)
Eslam S.A. BENDARY Ain Shams University, Faculty of Agriculture, Department of Agricultural Biochemistry, P.O. Box 68, Hadayek Shobra, Cairo 11241 (EG)

DOI:

https://doi.org/10.55779/nsb18112860

Keywords:

Musa peel, plant side stream, oxidative stress, monoaminergic neurotransmission, CREB signaling

Abstract

Depression is associated with oxidative stress, monoaminergic dysregulation, and impaired neuroplasticity. This study evaluated the effects of banana (Musa species) peel extract (MSPE) in a dexamethasone-induced rat model of depression. Five groups of adult male Wistar rats (n = 7 per group) were used, with four groups receiving dexamethasone (1 mg/kg, i.p., 14 days) to induce depressive-like alterations, while one group served as a normal control. Treated groups received MSPE (300 mg/kg, p.o.), fluoxetine (10 mg/kg), or their combination alongside dexamethasone. Behavioral assessment demonstrated depressive-like alterations in dexamethasone-exposed animals, which were partially ameliorated in MSPE-treated groups. Dexamethasone exposure significantly reduced superoxide dismutase (SOD) activity (75 ± 10 U/mg protein) and reduced glutathione (GSH; 3.5 ± 0.4 nmol/mg protein), while elevating malondialdehyde (MDA; 4.0 ± 0.5 nmol/mg protein), and markedly depleted brain serotonin (125 ± 30 ng/g) and dopamine (100 ± 20 ng/g), alongside a reduction in the p-CREB/CREB ratio to 0.6 ± 0.1 versus 1.2 ± 0.1 in controls (p < 0.01). MSPE treatment restored SOD to 160 ± 12 U/mg protein and GSH to 6.8 ± 0.6 nmol/mg protein, reduced MDA to 1.8 ± 0.3 nmol/mg protein, partially recovered serotonin (350 ± 45 ng/g) and dopamine (180–195 ng/g) levels, and elevated the p-CREB/CREB ratio to 1.0 ± 0.1 (p < 0.01 vs. dexamethasone group). LC–QTOF–MS profiling identified several polyphenolic constituents in MSPE, notably ferulic acid (206 µg/g DW), catechin (177 µg/g DW), rutin (158 µg/g DW), and hesperidin (152 µg/g DW), which may contribute to these effects. Combined MSPE and fluoxetine treatment produced biochemical responses comparable to or slightly greater than either treatment alone. Overall, these findings suggest that Musa peel extract may influence oxidative, monoaminergic, and CREB signaling pathways relevant to stress-related neurobiological alterations.

Metrics

Metrics Loading ...

References

Ahmed AR, Alqahtani NK, Ramadan KMA, Mohamed HI, Mahmoud MAA, Elkatry HO (2023). The bioactive substances in spent black tea and Arabic coffee could improve the nutritional value and extend the shelf life of sponge cake after fortification. ACS Omega 8(37):33593-33609. https://doi.org/10.1021/acsomega.3c03747

Ahmed AR, Ramadan KMA, Elkatry HO, Alqahtani NK, Bendary ESA, Ghuniem MM, Mahmoud MAA (2025). Valorization of date palm by-products (Phoenix dactylifera L.) in cake fortification: nutritional enrichment, antioxidant retention, and shelf-life extension. Food Chemistry: X 31:103184. https://doi.org/10.1016/j.fochx.2025.103184

Bradford MM (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72:248-254. https://doi.org/10.1016/0003-2697(76)90527-3

Du B, Tang X, Liu F, Zhang C, Zhao G, Ren F, Leng X (2014). Antidepressant-like effects of the hydroalcoholic extracts of Hemerocallis citrina and its potential active components. BMC Complementary and Alternative Medicine 14:326. https://doi.org/10.1186/1472-6882-14-326

El-Beltagi HS, El-Mogy MM, Parmar A, Mansour AT, Shalaby TA, Ali M (2022b). Phytochemical characterization and utilization of dried red beetroot (Beta vulgaris) peel extract in maintaining the quality of Nile Tilapia fish fillet. Antioxidants 11:906. https://doi.org/10.3390/antiox11050906

El-Beltagi HS, Eshak NS, Mohamed HI, Bendary ESA, Danial AW (2022a). Physical characteristics, mineral content, and antioxidant and antibacterial activities of Punica granatum or Citrus sinensis peel extracts and their applications to improve cake quality. Plants 11:1740. https://doi.org/10.3390/plants11131740.

Elkatry HO, El-Beltagi HS, Ahmed AR, Mohamed HI, Al-Otaibi HH, Ramadan KMA, Mahmoud MAA (2023). The potential use of Indian rice flour or husk in fortification of pan bread: assessing bread’s quality using sensory, physicochemical, and chemometric methods. Frontiers in Nutrition 10:1240527. https://doi.org/10.3389/fnut.2023.1240527

Elkatry HO, Ahmed AR, El-Beltagi HS, Mohamed HI, Eshak NS (2022). Biological activities of grape seed by-products and their potential use as natural sources of food additives in the production of balady bread. Foods 11:1948. https://doi.org/10.3390/foods11131948

Eshak NS (2016). Sensory evaluation and nutritional value of balady flat bread supplemented with banana peels as a natural source of dietary fiber. Annals of Agricultural Sciences 61:229-235. https://doi.org/10.1016/j.aoas.2016.07.002

Festing MF, Altman DG (2002). Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR Journal 43:244-258. https://doi.org/10.1093/ilar.43.4.244

Foudah AI, Alqarni MH, Alam A, Devi S, Salkini MA, Alam P (2022). Rutin improves anxiety and reserpine-induced depression in rats. Molecules 27:7313. https://doi.org/10.3390/molecules27217313

Javed H, Vaibhav K, Ahmed ME, Khan A, Tabassum R, Islam F, Safhi MM, Islam F (2015). Effect of hesperidin on neurobehavioral, neuroinflammation, oxidative stress and lipid alteration in intracerebroventricular streptozotocin induced cognitive impairment in mice. Journal of the Neurological Sciences 348:51-59. https://doi.org/10.1016/j.jns.2014.10.044

Jazvinšćak Jembrek M, Oršolić N, Karlović D, Peitl V (2023). Flavonols in action: targeting oxidative stress and neuroinflammation in major depressive disorder. International Journal of Molecular Sciences 24:6888. https://doi.org/10.3390/ijms24086888

Kandhwal M, Grewal AK, Singh V, Sharma O, Khan H, Singh M, Kumar A, Singh TG, Singh T, Ahmad SF, Al-Mazroua HA, Harisa GI (2025). Hesperidin attenuates chronic stress-induced depression via 5-HT2A-linked modulation of neurochemical, oxidative, and inflammatory pathways: experimental and in silico evidence. Neurochemical Research 50:310. https://doi.org/10.1007/s11064-025-04562-0

Kaur M, Singh B, Kaur A (2022). Influence of different oilseed cake incorporation on batter rheology, proximate composition, texture, antioxidant and sensory properties of wheat flour muffins. International Journal of Food Science and Technology 57:7107-7115.

Kulkarni S, Dhir A (2007). Effect of various classes of antidepressants in behavioral paradigms of despair. Progress in Neuro-Psychopharmacology and Biological Psychiatry 31:1248-1254.

Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, Youdim MBH (2005). Multifunctional activities of green tea catechins in neuroprotection: modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neuro-Signals 14:46-60. https://doi.org/10.1159/000085385

Nakajima K, Okubo S, Ohta T, Uto T, Oiso S (2023). Upregulation of brain-derived neurotrophic factor by Shiikuwasha (Citrus depressa Hayata). Journal of Pharmaceutical Health Care and Sciences 9:40. https://doi.org/10.1186/s40780-023-00309-7

Nassar A, Azab AN (2022). Effects of dexamethasone and pentoxifylline on mania-like and depression-like behaviors in rats. Pharmaceuticals 15:1063.

Rai A, Gill M, Kinra M, Shetty R, Krishnadas N, Rao CM, Sumalatha S, Kumar N (2019). Catechin ameliorates depressive symptoms in Sprague Dawley rats subjected to chronic unpredictable mild stress by decreasing oxidative stress. Biomedical Reports 11:79-84. https://doi.org/10.3892/br.2019.1226

Ramadan KM, El-Beltagi HS, Mohamed HI, Shalaby TA, Galal A, Mansour AT, Aboul Fotouh MM, Bendary ES (2022). Antioxidant, anti-cancer activity and phytochemicals profiling of Kigelia pinnata fruits. Separations. 9(11): 379. https://doi.org/10.3390/separations9110379

Ramadan KMA, Mahmoud MAA, El-Beltagi HS, Al-Hashedi SA, Yehyei SM, Oraby MM, Abou-Taleb KAA, Mohamed HA, Bendary ESA, Ismail AM, El-Mogy MM, Amin SA (2025). Sustainable fungal chitosan films for beef preservation: integrating microbial control, moisture retention, and multivariate quality analysis. Acta Alimentaria 54:736-752. https://doi.org/10.1556/066.2025.00243

Samad N, Muneer A, Ullah N, Zaman A, Ayaz MM, Ahmad I (2017). Banana fruit pulp and peel involved in antianxiety and antidepressant effects while invigorate memory performance in male mice: possible role of potential antioxidants. Pakistan Journal of Pharmaceutical Sciences 30:989-995.

Tongkaew P, Tohraman A, Bungaramphai R, Mitrpant C, Aydin E (2022). Kluai Hin (Musa sapientum Linn.) peel as a source of functional polyphenols identified by HPLC-ESI-QTOF-MS and its potential antidiabetic function. Scientific Reports 12:4145. https://doi.org/10.1038/s41598-022-08008-3

Xu Y, Zhang L, Shao T, Ruan L, Wang L, Sun J, Li J, Zhu X, O’Donnell JM, Pan J (2013). Ferulic acid increases pain threshold and ameliorates depression-like behaviors in reserpine-treated mice: behavioral and neurobiological analyses. Metabolic Brain Disease 28:571-583. https://doi.org/10.1007/s11011-013-9404-4

Yin C, Lu R, Zhu J, Huang H, Liu X, Li Q, Mo Y, Zhu H, Chin B, Wu J (2019). The study of neuroprotective effect of ferulic acid based on cell metabolomics. European Journal of Pharmacology 864:172694. https://doi.org/10.1016/j.ejphar.2019.172694

Zafir A, Banu N (2009). Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress 12:167-177. https://doi.org/10.1080/10253890802234168

Zeni ALB, Camargo A, Dalmagro AP (2017). Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice. Steroids 125:131-136. https://doi.org/10.1016/j.steroids.2017.07.006