Melissa officinalis L. hydro-alcoholic extract inhibits anxiety and depression through prevention of central oxidative stress and apoptosis

Javid Ghazizadeh, Sanaz Hamedeyazdan, Mohammadali Torbati, Fereshteh Farajdokht, Ali Fakhari, Javad Mahmoudi, Mostafa Araj-Khodaei, Saeed Sadigh-Eteghad, Javid Ghazizadeh, Sanaz Hamedeyazdan, Mohammadali Torbati, Fereshteh Farajdokht, Ali Fakhari, Javad Mahmoudi, Mostafa Araj-Khodaei, Saeed Sadigh-Eteghad

Abstract

New findings: What is the central question of this study? How does an extract of Melissa officinalis L. ameliorate anxiety- and depressive-like behaviour of mice? What is the main finding and its importance? An extract of Melissa officinalis L. possessed anxiolytic and anti-depressant effects, which could mainly be mediated through its antioxidant and anti-apoptotic properties.

Abstract: This study evaluated the effects of a hydro-alcoholic extract of Melissa officinalis (HAEMO) on anxiety- and depressive-like behaviours, oxidative stress and apoptosis markers in restraint stress-exposed mice. In order to induce a depression-like model, mice were subjected to restraint stress (3 h day-1 for 14 days) and received normal saline or HAEMO (50, 75 and 150 mg kg-1 day-1 ) for 14 days. The administered doses of HAEMO were designated based on the concentration of one of the main phenolic compounds present in the extract, rosmarinic acid (2.55 mg kg-1 at lowest dose); other phytochemical analyses including assays for antioxidant activity, total phenols and flavonoids were also carried out. The behavioural changes in an open field task, elevated plus maze, tail suspension and forced swimming tests were evaluated. Also, malondialdehyde (MDA) levels and enzyme activities of superoxide dismutase and glutathione peroxidase, and total antioxidant capacity were assessed in the prefrontal cortex and hippocampus. Moreover, levels of Bcl-2, Bax and caspase 3 in the brain as well as serum concentration of corticosterone were evaluated. HAEMO (75 and 150 mg kg-1 ) significantly reversed anxiety- and depressive-like behaviours. Also, HAEMO reduced MDA levels, enhanced enzymatic antioxidant activities and restored serum levels of corticosterone. An immunoblotting analysis also demonstrated that HAEMO decreased levels of pro-apoptotic markers and increased anti-apoptotic protein levels in the prefrontal cortex and hippocampus of restraint stress-exposed mice. Our findings suggested that HAEMO reduced inflammation and had anxiolytic and antidepressant effects in mice.

Keywords: Melissa officinalis; anxiety; apoptosis; depression; oxidative stress; restraint stress.

© 2020 Tabriz University of Medical Sciences. Experimental Physiology © 2020 The Physiological Society.

References

REFERENCES

    1. Alizadeh Behbahani, B., & Shahidi, F. (2019). Melissa officinalis essential oil: Chemical compositions, antioxidant potential, total phenolic content and antimicrobial activity. Nutrition and Food Sciences Research, 6(1), 17-25.
    1. Asghari, B., Mafakheri, S., Zarrabi, M. M., Erdem, S. A., Orhan, I. E., & Bahadori, M. B. (2019). Therapeutic target enzymes inhibitory potential, antioxidant activity, and rosmarinic acid content of Echium amoenum. South African Journal of Botany, 120, 191-197.
    1. Atif, F., Yousuf, S., & Agrawal, S. K. (2008). Restraint stress-induced oxidative damage and its amelioration with selenium. European Journal of Pharmacology, 600(1-3), 59-63.
    1. Awad, R., Muhammad, A., Durst, T., Trudeau, V. L., & Arnason, J. T. (2009). Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytotherapy Research, 23(8), 1075-1081.
    1. Bayat, M., Tameh, A. A., Ghahremani, M. H., Akbari, M., Mehr, S. E., Khanavi, M., & Hassanzadeh, G. (2012). Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo. DARU Journal of Pharmaceutical Sciences, 20(1), 42.
    1. Chakraborti, A., Gulati, K., Banerjee, B. D., & Ray, A. (2007). Possible involvement of free radicals in the differential neurobehavioral responses to stress in male and female rats. Behavioural Brain Research, 179(2), 321-325.
    1. Chemsa, A. E., Zellagui, A., Öztürk, M., Erol, E., Ceylan, O., Duru, M. E., & Lahouel, M. (2018). Chemical composition, antioxidant, anticholinesterase, antimicrobial and antibiofilm activities of essential oil and methanolic extract of Anthemis stiparum subsp. sabulicola (Pomel) Oberpr. Microbial Pathogenesis, 119, 233-240.
    1. Chiba, S., Numakawa, T., Ninomiya, M., Richards, M. C., Wakabayashi, C., & Kunugi, H. (2012). Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 39(1), 112-119.
    1. Christoffel, D. J., Golden, S. A., & Russo, S. J. (2011). Structural and synaptic plasticity in stress-related disorders. Reviews in the Neurosciences, 22(5), 535-549.
    1. Chu, X., Zhou, Y., Hu, Z., Lou, J., Song, W., Li, J., … Li, W. (2016). 24-hour-restraint stress induces long-term depressive-like phenotypes in mice. Scientific Reports, 6, 32935.
    1. Cui, H.-Y., Zhang, X.-J., Yang, Y., Zhang, C., Zhu, C.-H., Miao, J.-Y., & Chen, R. (2018). Rosmarinic acid elicits neuroprotection in ischemic stroke via Nrf2 and heme oxygenase 1 signaling. Neural Regeneration Research, 13(12), 2119-2128.
    1. Dastmalchi, K., Dorman, H. D., Oinonen, P. P., Darwis, Y., Laakso, I., & Hiltunen, R. (2008). Chemical composition and in vitro antioxidative activity of a lemon balm (Melissa officinalis L.) extract. LWT-Food Science and Technology, 41(3), 391-400.
    1. De Sousa, A. C., Gattass, C. R., Alviano, D. S., Alviano, C. S., Blank, A. F., & Alves, P. B. (2004). Melissa officinalis L. essential oil: Antitumoral and antioxidant activities. Journal of Pharmacy and Pharmacology, 56(5), 677-681.
    1. Emamghoreishi, M., & Talebianpour, M. (2009). Antidepressant effect of Melissa officinalis in the forced swimming test. DARU Journal of Pharmaceutical Sciences, 17(1), 42-47.
    1. Falé, P. L., Madeira, P. J. A., Florêncio, M. H., Ascensão, L., & Serralheiro, M. L. M. (2011). Function of Plectranthus barbatus herbal tea as neuronal acetylcholinesterase inhibitor. Food & Function, 2(2), 130-136.
    1. Feliú-Hemmelmann, K., Monsalve, F., & Rivera, C. (2013). Melissa officinalis and Passiflora caerulea infusion as physiological stress decreaser. International Journal of Clinical and Experimental Medicine, 6(6), 444-451.
    1. Fontella, F. U., Siqueira, I. R., Vasconcellos, A. P. S., Tabajara, A. S., Netto, C. A., & Dalmaz, C. (2005). Repeated restraint stress induces oxidative damage in rat hippocampus. Neurochemical Research, 30(1), 105-111.
    1. Ghadrdoost, B., Vafaei, A. A., Rashidy-Pour, A., Hajisoltani, R., Bandegi, A. R., Motamedi, F., … Pahlvan, S. (2011). Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. European Journal of Pharmacology, 667(1-3), 222-229.
    1. Gong, S., Zhang, J., Guo, Z., & Fu, W. (2018). Senkyunolide a protects neural cells against corticosterone-induced apoptosis by modulating protein phosphatase 2a and α-synuclein signaling. Drug Design, Development and Therapy, 12, 1865.
    1. Guo, C., Sun, L., Chen, X., & Zhang, D. (2013). Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Research, 8(21), 2003-2014.
    1. Hamza, A. A., Ahmed, M. M., Elwey, H. M., & Amin, A. (2016). Melissa officinalis protects against doxorubicin-induced cardiotoxicity in rats and potentiates its anticancer activity on MCF-7 cells. PLoS One, 11(11), e0167049.
    1. Hassanzadeh, G., Pasbakhsh, P., Akbari, M., Shokri, S., Ghahremani, M., Amin, G., … Azami Tameh, A. (2011). Neuroprotective properties of Melissa officinalis L. Extract against ecstasy-induced neurotoxicity. Cell Journal, 13(1), 25-30.
    1. Haybar, H., Javid, A. Z., Haghighizadeh, M. H., Valizadeh, E., Mohaghegh, S. M., & Mohammadzadeh, A. (2018). The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina. Clinical Nutrition ESPEN, 26, 47-52.
    1. Heydari, N., Dehghani, M., Emamghoreishi, M., & Akbarzadeh, M. (2018). Effect of Melissa officinalis capsule on the mental health of female adolescents with premenstrual syndrome: A clinical trial study. International Journal of Adolescent Medicine and Health 31(3), .
    1. Hovatta, I., Juhila, J., & Donner, J. (2010). Oxidative stress in anxiety and comorbid disorders. Neuroscience Research, 68(4), 261-275.
    1. Huang, P., Li, C., Fu, T., Zhao, D., Yi, Z., Lu, Q., … Xu, X. (2015). Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice. Behavioural Brain Research, 288, 1-10.
    1. Ibarra, A., Feuillere, N., Roller, M., Lesburgere, E., & Beracochea, D. (2010). Effects of chronic administration of Melissa officinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in mice. Phytomedicine, 17(6), 397-403.
    1. Jin, X., Liu, P., Yang, F., Zhang, Y.-h., & Miao, D. (2013). Rosmarinic acid ameliorates depressive-like behaviors in a rat model of CUS and up-regulates BDNF levels in the hippocampus and hippocampal-derived astrocytes. Neurochemical Research, 38(9), 1828-1837.
    1. Juszczak, G. R., Lisowski, P., Śliwa, A. T., & Swiergiel, A. H. (2008). Computer assisted video analysis of swimming performance in a forced swim test: Simultaneous assessment of duration of immobility and swimming style in mice selected for high and low swim-stress induced analgesia. Physiology & Behavior, 95(3), 400-407.
    1. Keller, J., Gomez, R., Williams, G., Lembke, A., Lazzeroni, L., Murphy, G. M., Jr., & Schatzberg, A. F. (2017). HPA axis in major depression: Cortisol, clinical symptomatology and genetic variation predict cognition. Molecular Psychiatry, 22(4), 527-536.
    1. Khamse, S., Sadr, S. S., Roghani, M., Rashvand, M., Mohammadian, M., & Marefati, N. (2018) Rosmarinic acid mitigates apoptosis and nNOS immunoreactivity but not MAPK and COX-2, following intrahippocampal kainic acid in the rat. Basic and Clinical Neuroscience,
    1. Khan, S., & Khan, R. A. (2017). Chronic stress leads to anxiety and depression. Annals of Psychiatry & Mental Health, 5(1), 1091.
    1. Khodaei, M. A., Noorbala, A. A., Parsian, Z., Targhi, S. T., Emadi, F., Alijaniha, F., … Zargaran, A. (2017). Avicenna (980-1032CE): The pioneer in treatment of depression. Transylvanian Review, 25(17), .
    1. Kim, E. J., Pellman, B., & Kim, J. J. (2015). Stress effects on the hippocampus: A critical review. Learning & Memory, 22(9), 411-416.
    1. Komes, D., Belscak-Cvitanovic, A., Horzic, D., Rusak, G., Likic, S., & Berendika, M. (2011). Phenolic composition and antioxidant properties of some traditionally used medicinal plants affected by the extraction time and hydrolysis. Phytochemical Analysis, 22(2), 172-180.
    1. Kondo, S., El Omri, A., Han, J., & Isoda, H. (2015). Antidepressant-like effects of rosmarinic acid through mitogen-activated protein kinase phosphatase-1 and brain-derived neurotrophic factor modulation. Journal of Functional Foods, 14, 758-766.
    1. Kubera, M., Obuchowicz, E., Goehler, L., Brzeszcz, J., & Maes, M. (2011). In animal models, psychosocial stress-induced (neuro) inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(3), 744-759.
    1. Lee, H. J., Cho, H.-S., Park, E., Kim, S., Lee, S.-Y., Kim, C.-S., … Chun, H. S. (2008). Rosmarinic acid protects human dopaminergic neuronal cells against hydrogen peroxide-induced apoptosis. Toxicology, 250(2), 109-115.
    1. Lee, S.-Y., Lee, S.-J., Han, C., Patkar, A. A., Masand, P. S., & Pae, C.-U. (2013). Oxidative/nitrosative stress and antidepressants: Targets for novel antidepressants. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 46, 224-235.
    1. Lépine, J.-P., & Briley, M. (2011). The increasing burden of depression. Neuropsychiatric Disease and Treatment, 7(Suppl 1), 3.
    1. Lin, S.-H., Chou, M.-L., Chen, W.-C., Lai, Y.-S., Lu, K.-H., Hao, C.-W., & Sheen, L.-Y. (2015). A medicinal herb, Melissa officinalis L. ameliorates depressive-like behavior of rats in the forced swimming test via regulating the serotonergic neurotransmitter. Journal of Ethnopharmacology, 175, 266-272.
    1. Liu, B., Zhang, H., Xu, C., Yang, G., Tao, J., Huang, J., … Dong, J. (2011). Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons. Brain research, 1375, 59-67.
    1. Liu, T., Zhong, S., Liao, X., Chen, J., He, T., Lai, S., & Jia, Y. (2015). A meta-analysis of oxidative stress markers in depression. PLoS One, 10(10), e0138904.
    1. López, V., Martín, S., Gómez-Serranillos, M. P., Carretero, M. E., Jäger, A. K., & Calvo, M. I. (2009). Neuroprotective and neurological properties of Melissa officinalis. Neurochemical Research, 34(11), 1955-1961.
    1. Lopresti, A. L. (2019). Mitochondrial dysfunction and oxidative stress: Relevance to the pathophysiology and treatment of depression. In: J. Quevedo, A. F. Carvalho, & C. A. Zarate (Eds), Neurobiology of Depression (pp. 159-168),
    1. Maes, M., Galecki, P., Chang, Y. S., & Berk, M. (2011). A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(3), 676-692.
    1. Maes, M., Landucci Bonifacio, K., Morelli, N. R., Vargas, H. O., Barbosa, D. S., Carvalho, A. F., & Nunes, S. O. V. (2019). Major differences in neurooxidative and neuronitrosative stress pathways between major depressive disorder and types I and II bipolar disorder. Molecular Neurobiology, 56(1), 141-156.
    1. Mahboubi, M. (2019). Melissa officinalis and rosmarinic acid in management of memory functions and Alzheimer disease. Asian Pacific Journal of Tropical Biomedicine, 9(2), 47-52.
    1. Mahmoudi, J., Farhoudi, M., Talebi, M., Sabermarouf, B., & Sadigh-Eteghad, S. (2015). Antidepressant-like effect of modafinil in mice: Evidence for the involvement of the dopaminergic neurotransmission. Pharmacological Reports, 67(3), 478-484.
    1. Majdi, A., Sadigh-Eteghad, S., Talebi, M., Farajdokht, F., Erfani, M., Mahmoudi, J., & Gjedde, A. (2018). Nicotine modulates cognitive function in D-galactose-induced senescence in mice. Frontiers in Aging Neuroscience, 10, 194.
    1. Makhathini, K. B., Mabandla, M. V., & Daniels, W. M. (2018). Rosmarinic acid reverses the deleterious effects of repetitive stress and tat protein. Behavioural Brain Research, 353, 203-209.
    1. Martins, E. N., Pessano, N. T. C., Leal, L., Roos, D. H., Folmer, V., Puntel, G. O., … Puntel, R. L. (2012). Protective effect of Melissa officinalis aqueous extract against Mn-induced oxidative stress in chronically exposed mice. Brain Research Bulletin, 87(1), 74-79.
    1. McEwen, B. S. (2008). Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. European Journal of Pharmacology, 583(2-3), 174-185.
    1. McEwen, B. S., Nasca, C., & Gray, J. D. (2016). Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology, 41(1), 3-23.
    1. Méndez-Armenta, M., Nava-Ruíz, C., Juárez-Rebollar, D., Rodríguez-Martínez, E., & Yescas Gómez, P. (2014). Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxidative Medicine and Cellular Longevity, 2014, 293689.
    1. Miraj, S., Rafieian, K., & Kiani, S. (2017). Melissa officinalis L: A review study with an antioxidant prospective. Journal of Evidence-based Complementary & Alternative Medicine, 22(3), 385-394.
    1. Moacă, E.-A., Farcaş, C., Ghiţu, A., Coricovac, D., Popovici, R., Cărăba-Meiţă, N.-L., … Avram, Ş. (2018). A comparative study of melissa officinalis leaves and stems ethanolic extracts in terms of antioxidant, cytotoxic, and antiproliferative potential. Evidence-Based Complementary and Alternative Medicine, 2018, 7860456.
    1. Mohammadi, A. B., Torbati, M., Farajdokht, F., Sadigh-Eteghad, S., Fazljou, S. M. B., Vatandoust, S. M., … Mahmoudi, J. (2019). Sericin alleviates restraint stress induced depressive-and anxiety-like behaviors via modulation of oxidative stress, neuroinflammation and apoptosis in the prefrontal cortex and hippocampus. Brain Research, 1715, 47-56.
    1. Moretti, M., Budni, J., Dos Santos, D. B., Antunes, A., Daufenbach, J. F., Manosso, L. M., … Rodrigues, A. L. S. (2013). Protective effects of ascorbic acid on behavior and oxidative status of restraint-stressed mice. Journal of Molecular Neuroscience, 49(1), 68-79.
    1. Murphy, B. E. P. (1991). Steroids and depression. The Journal of Steroid Biochemistry and Molecular Biology, 38(5), 537-559.
    1. Pandian Selvan, M., & Rajan, R. (2016). Effect of 4-allyl-2-methoxyphenol (eugenol) on motor co-ordination in subacute restraint stress induced wistar albino rats. Journal of Applied Pharmaceutical Science Vol, 6(11), 120-125.
    1. Pereira, P., Tysca, D., Oliveira, P., da Silva Brum, L. F., Picada, J. N., & Ardenghi, P. (2005). Neurobehavioral and genotoxic aspects of rosmarinic acid. Pharmacological Research, 52(3), 199-203.
    1. Poh Loh, K., Hong Huang, S., De Silva, R., Tan, H., Benny, K., & Zhun Zhu, Y. (2006). Oxidative stress: Apoptosis in neuronal injury. Current Alzheimer Research, 3(4), 327-337.
    1. Pourmemar, E., Majdi, A., Haramshahi, M., Talebi, M., Karimi, P., & Sadigh-Eteghad, S. (2017). Intranasal cerebrolysin attenuates learning and memory impairments in D-galactose-induced senescence in mice. Experimental Gerontology, 87(A), 16-22.
    1. Saberi, A., Abbasloo, E., Sepehri, G., Yazdanpanah, M., Mirkamandari, E., Sheibani, V., & Safi, Z. (2016). The effects of methanolic extract of melissa officinalis on experimental gastric ulcers in rats. Iranian Red Crescent Medical Journal, 18(7), e24271-e24271.
    1. Salehpour, F., Farajdokht, F., Cassano, P., Sadigh-Eteghad, S., Erfani, M., Hamblin, M. R., … Mahmoudi, J. (2019). Near-infrared photobiomodulation combined with coenzyme Q10 for depression in a mouse model of restraint stress: Reduction in oxidative stress, neuroinflammation, and apoptosis. Brain Research Bulletin, 144, 213-222.
    1. Salim, S. (2017). Oxidative stress and the central nervous system. The Journal of Pharmacology and Experimental Therapeutics, 360(1), 201-205.
    1. Schiavone, S., Jaquet, V., Trabace, L., & Krause, K.-H. (2013). Severe life stress and oxidative stress in the brain: From animal models to human pathology. Antioxidants & Redox Signaling, 18(12), 1475-1490.
    1. Smaga, I., Niedzielska, E., Gawlik, M., Moniczewski, A., Krzek, J., Przegaliński, E., … Filip, M. (2015). Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism. Pharmacological Reports, 67(3), 569-580.
    1. Smith, S. M., & Vale, W. W. (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in Clinical Neuroscience, 8(4), 383-395.
    1. Soodi, M., Dashti, A., Hajimehdipoor, H., Akbari, S., & Ataei, N. (2017). Melissa officinalis acidic fraction protects cultured cerebellar granule neurons against beta amyloid-induced apoptosis and oxidative stress. Cell Journal (Yakhteh), 18(4), 556.
    1. Spiers, J. G., Chen, H.-J. C., Sernia, C., & Lavidis, N. A. (2015). Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress. Frontiers in Neuroscience, 8(456), 456.
    1. Taiwo, A. E., Leite, F. B., Lucena, G. M., Barros, M., Silveira, D., Silva, M. V., & Ferreira, V. M. (2012). Anxiolytic and antidepressant-like effects of Melissa officinalis (lemon balm) extract in rats: Influence of administration and gender. Indian Journal of Pharmacology, 44(2), 189-192.
    1. Takeda, H., Tsuji, M., Inazu, M., Egashira, T., & Matsumiya, T. (2002). Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice. European Journal of Pharmacology, 449(3), 261-267.
    1. Taram, F., Ignowski, E., Duval, N., & Linseman, D. A. (2018). Neuroprotection comparison of rosmarinic acid and carnosic acid in primary cultures of cerebellar granule neurons. Molecules, 23(11), 2956.
    1. Teague, C. R., Dhabhar, F. S., Barton, R. H., Beckwith-Hall, B., Powell, J., Cobain, M., … Nicholson, J. K. (2007). Metabonomic studies on the physiological effects of acute and chronic psychological stress in Sprague−Dawley rats. Journal of Proteome Research, 6(6), 2080-2093.
    1. Torres, I. L. d. S., Gamaro, G. D., Silveira-Cucco, S., Michalowski, M. B., Corrêa, J., Perry, M. L. S., & Dalmaz, C. (2001). Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices. Brazilian Journal of Medical and Biological Research, 34(1), 111-116.
    1. Ulbricht, C., Brendler, T., Gruenwald, J., Kligler, B., Keifer, D., Abrams, T., … Hackman, D. (2005). Lemon balm (Melissa officinalis L.): An evidence-based systematic review by the Natural Standard Research Collaboration. Journal of Herbal Pharmacotherapy, 5(4), 71-114.
    1. Wong, M.-L., & Licinio, J. (2004). From monoamines to genomic targets: A paradigm shift for drug discovery in depression. Nature Reviews Drug Discovery, 3(2), 136.
    1. Woo, H., Hong, C. J., Jung, S., Choe, S., & Yu, S.-W. (2018). Chronic restraint stress induces hippocampal memory deficits by impairing insulin signaling. Molecular Brain, 11(1), 37.
    1. World Health Organization (2007). Task shifting: Rational redistribution of tasks among health workforce teams: Global recommendations and guidelines. Geneva: World Health Organization.
    1. World Health Organization (2017). Depression and other common mental disorders: Global health estimates. Geneva: World Health Organization.
    1. Yang, L., Zhao, Y., Wang, Y., Liu, L., Zhang, X., Li, B., & Cui, R. (2015). The effects of psychological stress on depression. Current Neuropharmacology, 13(4), 494-504.
    1. Yoo, D. Y., Choi, J. H., Kim, W., Yoo, K.-Y., Lee, C. H., Yoon, Y. S., … Hwang, I. K. (2011). Effects of Melissa officinalis L. (lemon balm) extract on neurogenesis associated with serum corticosterone and GABA in the mouse dentate gyrus. Neurochemical Research, 36(2), 250-257.
    1. Zaidi, S. K. R., Al-Qirim, T. M., & Banu, N. (2005). Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation induced by restraint stress in the rat liver. Drugs in R & D, 6(3), 157-165.

Source: PubMed

Подписаться