• EMNI PURWONINGSIH Doctoral Program in Biomedical Science Faculty of Medicine University of Indonesia. Jl. Salemba Raya no. 6, Kenari, Kec. Senen, Jakarta Pusat, DKI Jakarta, Indonesia 10430, Faculty of Medicine, Universitas Muhammadiyah Sumatera Utara. Jl. Gedung Arca no.53, North Sumatera 20217
  • WAWAIMULI AROZAL Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Jl. Salemba Raya no. 6, Kenari, Kec. Senen, Jakarta Pusat, DKI Jakarta, Indonesia 10430
  • HEE J. LEE Kangwon National University, South Korea
  • ABDUL MUNIM Faculty of Pharmacy, University of Indonesia, Jl. Prof. Dr. Mahar Mardjono, Pondok Cina, Beji, Depok City, West Java, Indonesia 16424



Moringa oleifera, Anxiety, Oxidative stress, Antioxidant, Chronic stress


Objective: To investigate the neuroprotective and antioxidant effects of leaves aqueous extract Moringa oleifera (MW) in chronic stress mouse models.

Methods: Water immersion and stress restraint for 16 d to obtain a chronic stress model animal. Moringa extract flour dissolved in Aquades, dose 800 mg/kg for 23 d, for chronic Stress+MOW group. Fluoxetine in aquades at a dose of 18 mg/kg BW for 23 d for chronic stress group+Fluoxetine. Aquades were given to normal mice (group N), and mice under chronic stress conditions (chronic stress control group). Furthermore, measure behavioral abnormalities by testing depressive behavior and oxidative stress parameters such as anxiety, Brain-derived neurotrophic factors (BDNF).

Results: Moringa oleifera water extract administration can improve behavioral disorders caused by stress by decreasing immobility time on the Force swim test, increasing time in the middle area, and increasing the number of returns to center areas on the Open field test. When chronically stressed mice were given fluoxetine and MOW, their MDA levels (p=0.008 and 0.041, respectively) and SOD activity (p=0.001 and 0.004) decreased significantly compared to the chronic stress control group. In contrast, Catalase activity increased significantly in chronically stressed mice given fluoxetine and MOW compared to the chronic stress control group (p=0.010 and 0.013). Administration of fluoxetine and MOW may increase the expression of mRNA BDNF compared to the chronic stress control group (p=0.000 and 0.013).

Conclusion: The study found that MOW can improve behavioral abnormalities, namely anxiety and depression behavior caused by chronic stress exposure, through antioxidant pathways and oxidant systems, and also BDNF


Download data is not yet available.


Zhang XY, Chen DC, Tan YL, Tan SP, Wang ZR, Yang FD. The interplay between BDNF and oxidative stress in chronic schizophrenia. Psychoneuroendocrinology. 2015 Jan;51:201-8. doi: 10.1016/j.psyneuen.2014.09.029. PMID 25462893.

Miao Z, Wang Y, Sun Z. The relationships between stress, mental disorders, and epigenetic regulation of BDNF. Int J Mol Sci. 2020 Feb 18;21(4):1375. doi: 10.3390/ijms21041375, PMID 32085670, PMCID PMC7073021.

Notaras M, van den Buuse M. Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders. Mol Psychiatry. 2020 Oct;25(10):2251-74. doi: 10.1038/s41380-019-0639-2. PMID 31900428.

Herbet M, Szumełda I, Piątkowska Chmiel I, Gawronska Grzywacz M, Dudka J. Beneficial effects of combined administration of fluoxetine and mitochondria-targeted antioxidant at in behavioural and molecular studies in mice model of depression. Behav Brain Res. 2021 May 7;405:113185. doi: 10.1016/j.bbr.2021.113185. PMID 33617903.

Salim S. Oxidative stress and psychological disorders. Curr Neuropharmacol. 2014 Mar;12(2):140-7. doi: 10.2174/1570159X11666131120230309, PMID 24669208, PMCID PMC3964745.

Bhattacharya A, Tiwari P, Sahu PK, Kumar S. A review of the phytochemical and pharmacological characteristics of Moringa oleifera. J Pharm Bioallied Sci. 2018 Oct-Dec;10(4):181-91. doi: 10.4103/JPBS.JPBS_126_18, PMID 30568375.

Valdez Solana MA, Mejia Garcia VY, Tellez Valencia A, Garcia Arenas G, Salas Pacheco J, Alba Romero JJ. Nutritional content and elemental and phytochemical analyses of Moringa oleifera grown in Mexico. J Chem. 2015 Apr;2015:1-9. doi: 10.1155/2015/860381.

Ingale S, Gandhi F. Effect of aqueous extract of Moringa oleifera leaves on pharmacological models of epilepsy and anxiety in mice. Int J Epilepsy. 2016;03(1):12-9. doi: 10.1016/j.ijep.2016.02.001.

Joy A, Bhat S. Antianxiety effect of ethanolic extract of leaves of Moringa oleifera in swiss albino mice. Arch Med Health Sci. 2014;2(1):5-7. doi: 10.4103/2321-4848.133771.

Yasugaki S, Liu CY, Kashiwagi M, Kanuka M, Honda T, Miyata S. Effects of 3 weeks of water immersion and restraint stress on sleep in mice. Front Neurosci. 2019 Oct 14;13:1072. doi: 10.3389/fnins.2019.01072, PMID 31680813, PMCID PMC6813282.

Arozal W, Purwoningsih E, Lee HJ, Barinda AJ, Munim A. Effects of Moringa oleifera in two independents formulation and as a neuroprotective agent against scopolamine-induced memory impairment in mice. Front Nutr. 2022 Mar 1;9:799127. doi: 10.3389/fnut.2022.799127, PMID 35299766, PMCID PMC8922057.

Park C, Rosenblat JD, Brietzke E, Pan Z, Lee Y, Cao B. Stress, epigenetics and depression: A systematic review. Neurosci Biobehav Rev. 2019 Jul;102:139-52. doi: 10.1016/j.neubiorev.2019.04.010. PMID 31005627.

Kraeuter AK, Guest PC, Sarnyai Z. The open field test for measuring locomotor activity and anxiety-like behavior. Methods Mol Biol. 2019;1916:99-103. doi: 10.1007/978-1-4939-8994-2_9, PMID 30535687.

Seibenhener ML, Wooten MC. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp. 2015 Feb 6;96(96):e52434. doi: 10.3791/52434, PMID 25742564, PMCID PMC4354627.

Kraeuter AK, Guest PC, Sarnyai Z. The forced swim test for depression-like behavior in rodents. Methods Mol Biol. 2019;1916:75-80. doi: 10.1007/978-1-4939-8994-2_5, PMID 30535683.

Valvassori S, Varela RB, Quevedo J. Animal models of mood disorders: focus on bipolar disorder and depression. In: Animal models for the study of human disease. 2nd ed. Academic Press; 2017. p. 991-100. doi: 10.1016/B978-0-12-809468-6.00038-3.

Can A, Dao DT, Arad M, Terrillion CE, Piantadosi SC, Gould TD. The mouse forced swim test. J Vis Exp. 2012;59(59):e3638. doi: 10.3791/3638, PMID 22314943.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248-54. doi: 10.1006/abio.1976.9999, PMID 942051.

Mir S, Cai W, Andres DA. RIT1 GTPase regulates Sox2 transcriptional activity and hippocampal neurogenesis. J Biol Chem. 2017 Feb 10;292(6):2054-64. doi: 10.1074/jbc.M116.749770. PMID 28007959, PMCID PMC5313081.

Yankelevitch Yahav R, Franko M, Huly A, Doron R. The forced swim test as a model of depressive-like behavior. J Vis Exp. 2015 Mar 2;97(97):52587. doi: 10.3791/52587, PMID 25867960, PMCID PMC4401172.

Moreno Martinez S, Tendilla Beltran H, Sandoval V, Flores G, Terron JA. Chronic restraint stress induces anxiety-like behavior and remodeling of dendritic spines in the central nucleus of the amygdala. Behav Brain Res. 2022 Jan 7;416:113523. doi: 10.1016/j.bbr.2021.113523. PMID 34390801.

Cotella EM, Gomez AS, Lemen P, Chen C, Fernandez G, Hansen C. Long-term impact of chronic variable stress in adolescence versus adulthood. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jan 10;88:303-10. doi: 10.1016/j.pnpbp.2018.08.003. PMID 30096330, PMCID PMC6165677.

Mahmoud MS, El-Kott AF, AlGwaiz HIM, Fathy SM. Protective effect of Moringa oleifera Lam. leaf extract against oxidative stress, inflammation, depression, and apoptosis in a mouse model of hepatic encephalopathy. Environ Sci Pollut Res Int. 2022 Nov;29(55):83783-96. doi: 10.1007/s11356-022-21453-x. PMID 35771324.

Bajpai A, Verma AK, Srivastava M, Srivastava R. Oxidative stress and major depression. J Clin Diagn Res. 2014 Dec;8(12):CC04-7. doi: 10.7860/JCDR/2014/10258.5292. PMID 25653939, PMCID PMC4316245.

Vargas HO, Nunes SO, de Castro MR, Vargas MM, Barbosa DS, Bortolasci CC. Oxidative stress and inflammatory markers are associated with depression and nicotine dependence. Neurosci Lett. 2013 Jun 7;544:136-40. doi: 10.1016/j.neulet.2013.03.059. PMID 23583694.

Huo L, Lu X, Wu F, Chang C, Ning Y, Zhang XY. Elevated activity of superoxide dismutase in male late-life schizophrenia and its correlation with clinical symptoms and cognitive deficits. BMC Psychiatry. 2021 Dec 4;21(1):606. doi: 10.1186/s12888-021-03604-5, PMID 34863137, PMCID PMC8642951.

Nandi A, Yan LJ, Jana CK, Das N. Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxid Med Cell Longev. 2019 Nov 11;2019:9613090. doi: 10.1155/2019/9613090, PMID 31827713, PMCID PMC6885225.

Lamou B, Taiwe GS, Hamadou A, Abene, Houlray J, Atour MM. Antioxidant and antifatigue properties of the aqueous extract of Moringa oleifera in rats subjected to forced swimming endurance test. Oxid Med Cell Longev. 2016;2016:3517824. doi: 10.1155/2016/3517824. PMID 26904162, PMCID PMC4745945.

Juszczyk G, Mikulska J, Kasperek K, Pietrzak D, Mrozek W, Herbet M. Chronic stress and oxidative stress as common factors of the pathogenesis of depression and Alzheimer’s disease: the role of antioxidants in prevention and treatment. Antioxidants (Basel). 2021 Sep 9;10(9):1439. doi: 10.3390/antiox10091439, PMID 34573069, PMCID PMC8470444.

Bhattacharya A, Tiwari P, Sahu PK, Kumar S. A review of the phytochemical and pharmacological characteristics of Moringa oleifera. J Pharm Bioallied Sci. 2018 Oct-Dec;10(4):181-91. doi: 10.4103/JPBS.JPBS_126_18, PMID 30568375.

Duranti G, Maldini M, Crognale D, Horner K, Dimauro I, Sabatini S. Moringa oleifera Leaf extract upregulates Nrf2/HO-1 expression and ameliorates redox status in C2C12 skeletal muscle cells. Molecules. 2021 Aug 20;26(16):5041. doi: 10.3390/molecules26165041, PMID 34443628, PMCID PMC8400669.

Bjorkholm C, Monteggia LM. BDNF–a key transducer of antidepressant effects. Neuropharmacology. 2016 Mar;102:72-9. doi: 10.1016/j.neuropharm.2015.10.034. PMID 26519901, PMCID PMC4763983.

Lee BH, Kim YK. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investig. 2010 Dec;7(4):231-5. doi: 10.4306/pi.2010.7.4.231. PMID 21253405, PMCID PMC3022308.

Kaur G, Invally M, Sanzagiri R, Buttar HS. Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine. J Ayurveda Integr Med. 2015 Oct-Dec;6(4):273-9. doi: 10.4103/0975-9476.172384, PMID 26834427, PMCID PMC4719488.



How to Cite




Original Article(s)