{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T23:14:02Z","timestamp":1783638842360,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,29]],"date-time":"2024-12-29T00:00:00Z","timestamp":1735430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004071","name":"Research and Technology Transfer Affair, Khon Kaen University","doi-asserted-by":"publisher","award":["FF2566\/NSRF2566"],"award-info":[{"award-number":["FF2566\/NSRF2566"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004071","name":"Research and Technology Transfer Affair, Khon Kaen University","doi-asserted-by":"publisher","award":["RP64-4\/009"],"award-info":[{"award-number":["RP64-4\/009"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004071","name":"Research and Technology Transfer Affair, Khon Kaen University","doi-asserted-by":"publisher","award":["2(1)\/2562"],"award-info":[{"award-number":["2(1)\/2562"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004071","name":"Research Program of Khon Kaen University","doi-asserted-by":"publisher","award":["FF2566\/NSRF2566"],"award-info":[{"award-number":["FF2566\/NSRF2566"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004071","name":"Research Program of Khon Kaen University","doi-asserted-by":"publisher","award":["RP64-4\/009"],"award-info":[{"award-number":["RP64-4\/009"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004071","name":"Research Program of Khon Kaen University","doi-asserted-by":"publisher","award":["2(1)\/2562"],"award-info":[{"award-number":["2(1)\/2562"]}],"id":[{"id":"10.13039\/501100004071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faculty of Pharmaceutical Sciences, Khon Kaen University","award":["FF2566\/NSRF2566"],"award-info":[{"award-number":["FF2566\/NSRF2566"]}]},{"name":"Faculty of Pharmaceutical Sciences, Khon Kaen University","award":["RP64-4\/009"],"award-info":[{"award-number":["RP64-4\/009"]}]},{"name":"Faculty of Pharmaceutical Sciences, Khon Kaen University","award":["2(1)\/2562"],"award-info":[{"award-number":["2(1)\/2562"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background Chronic stress exposure has been widely recognized as a significant contributor to numerous central nervous system (CNS) disorders, leading to debilitating behavioral changes such as anxiety, depression, and cognitive impairments. The prolonged activation of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis during chronic stress disrupts the neuroendocrine balance and has detrimental effects on neuronal function and survival. Nelumbo nucifera (N. nucifera) Gaertn., commonly known as the lotus flower, is a traditional medicinal plant consumed for its purported benefits on mental and physical well-being. Despite its traditional use, limited scientific evidence supports these claims. Methods The present study explores the effects of N. nucifera, commonly known as the lotus flower, on cognitive performance and stress resilience in a mouse model subjected to unpredictable chronic mild stress (UCMS). Results Daily treatment significantly improved cognitive performance, alleviated depressive-like behaviors, and normalized hypothalamic\u2013pituitary\u2013adrenal (HPA) axis activity, as indicated by a 60.97% reduction in serum corticosterone. At the molecular level, N. nucifera petals also downregulated serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression while upregulating brain-derived neurotrophic factor (BDNF) mRNA expression and cyclic-adenosine monophosphate (cAMP) responsive element-binding protein (CREB) mRNA expression in the hippocampus and frontal cortex. These normalizations are critical, as chronic stress dysregulates HPA axis function, exacerbating behavioral changes. Furthermore, a phytochemical analysis resulted in the isolation of five major compounds, kaempferol (1), trifolin (2), kaempferol-3-neohesperidoside (3), icariside D2 (4), and \u03b2-sitosterol (5), each demonstrating significant monoamine oxidase (MAO) inhibitory activity. Conclusions These compelling findings suggest that N. nucifera petals not only alleviate stress-induced mood and cognitive deficits but also offer a promising avenue for modulating the HPA axis and promoting neuroprotection via essential neurotrophic factors and enzymatic pathways. We advocate for its potential as a complementary and alternative medicine for effective stress management. Future investigations should further explore its mechanisms of action and evaluate its clinical applicability in stress-related disorders.<\/jats:p>","DOI":"10.3390\/nu17010094","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T12:51:24Z","timestamp":1735822284000},"page":"94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nelumbo nucifera Petals Ameliorate Depressive-like Symptom and Cognitive Deficit in Unpredictable Chronic Mild Stress Mouse Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9926-7092","authenticated-orcid":false,"given":"Juthamart","family":"Maneenet","sequence":"first","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-4984","authenticated-orcid":false,"given":"Yutthana","family":"Chotritthirong","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf M.","family":"Omar","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rattanathorn","family":"Choonong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2051-9953","authenticated-orcid":false,"given":"Supawadee","family":"Daodee","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7331-8373","authenticated-orcid":false,"given":"Orawan","family":"Monthakantirat","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9927-0670","authenticated-orcid":false,"given":"Charinya","family":"Khamphukdee","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supaporn","family":"Pitiporn","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Chao Phya Abhaibhubejhr Hospital, Ministry of Public Health, Prachinburi 25000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-193X","authenticated-orcid":false,"given":"Suresh","family":"Awale","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinzo","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Daiichi University of Pharmacy, Fukuoka 815-8511, Japan"},{"name":"Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7317-8721","authenticated-orcid":false,"given":"Yaowared","family":"Chulikhit","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nochaiwong, S., Ruengorn, C., Thavorn, K., Hutton, B., Awiphan, R., Phosuya, C., Ruanta, Y., Wongpakaran, N., and Wongpakaran, T. (2021). Global prevalence of mental health issues among the general population during the coronavirus disease-2019 pandemic: A systematic review and meta-analysis. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-89700-8"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yubonpunt, P., Kunno, J., Supawattanabodee, B., Sumanasrethakul, C., and Wiriyasirivaj, B. (2022). Prevalence of perceived stress and coping strategies among healthcare workers during the COVID-19 outbreak at Bangkok metropolitan, Thailand. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0270924"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ganesan, B., Al-Jumaily, A., Fong, K.N.K., Prasad, P., Meena, S.K., and Tong, R.K. (2021). Impact of coronavirus disease 2019 (COVID-19) outbreak quarantine, isolation, and lockdown policies on mental health and suicide. Front. Psychiatry, 16.","DOI":"10.3389\/fpsyt.2021.565190"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.neubiorev.2013.11.009","article-title":"Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects","volume":"38","author":"Mahar","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.nlm.2013.09.017","article-title":"Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: From adaptive responses to psychopathologies","volume":"112","author":"Finsterwald","year":"2014","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"929","DOI":"10.2174\/1570159X20666220103140834","article-title":"The role of natural products in treatment of depressive disorder","volume":"20","author":"Noori","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dattilo, V., Amato, R., Perrotti, N., and Gennarelli, M. (2020). The emerging role of SGK1 (serum- and glucocorticoid-regulated kinase 1) in major depressive disorder: Hypothesis and mechanisms. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00826"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3892\/ijmm.2016.2591","article-title":"Icariin alters the expression of glucocorticoid receptor, FKBP5 and SGK1 in rat brains following exposure to chronic mild stress","volume":"38","author":"Wei","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Maneenet, J., Monthakantirat, O., Daodee, S., Boonyarat, C., Chotritthirong, Y., Kwankhao, P., Pitiporn, S., Awale, S., and Chulikhit, Y. (2021). Merging the multi-target effects of Kleeb Bua Daeng, a Thai traditional herbal formula in unpredictable chronic mild stress-induced depression. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070659"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.biopsych.2006.02.013","article-title":"A neurotrophic model for stress-related mood disorders","volume":"59","author":"Duman","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113625","DOI":"10.1016\/j.jep.2020.113625","article-title":"The antidepressant-like effects of the water extract of Panax ginseng and Polygala tenuifolia are mediated via the BDNF-TrkB signaling pathway and neurogenesis in the hippocampus","volume":"267","author":"Jiang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.euroneuro.2017.07.008","article-title":"Neuroplasticity-related mechanisms underlying the antidepressant-like effects of traditional herbal medicines","volume":"27","author":"Hirshler","year":"2017","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"789124","DOI":"10.1155\/2015\/789124","article-title":"Phytochemical profile and biological activity of Nelumbo nucifera","volume":"2015","author":"Paudel","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tungmunnithum, D., Pinthong, D., and Hano, C. (2018). Flavonoids from Nelumbo nucifera Gaertn., a medicinal plant: Uses in traditional medicine, phytochemistry and pharmacological activities. Medicines, 5.","DOI":"10.3390\/medicines5040127"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11011-018-0324-1","article-title":"Effect of Nelumbo nucifera fruit on scopolamine induced memory deficits and motor coordination","volume":"34","author":"Khan","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.nutres.2014.01.003","article-title":"Ethanol extract of lotus (Nelumbo nucifera) root exhibits an anti-adipogenic effect in human pre-adipocytes and anti-obesity and anti-oxidant effects in rats fed a high-fat diet","volume":"34","author":"You","year":"2014","journal-title":"Nutr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"He, Y., Tao, Y., Qiu, L., Xu, W., Huang, X., Wei, H., and Tao, X. (2022). Lotus (Nelumbo nucifera Gaertn.) Leaf-Fermentation Supernatant Inhibits Adipogenesis in 3T3-L1 Preadipocytes and Suppresses Obesity in High-Fat Diet-Induced Obese Rats. Nutrients, 14.","DOI":"10.3390\/nu14204348"},{"key":"ref_18","unstructured":"Ministry of Public Health (2019). Thai Hercal Pharmacopoeia, Ministry of Public Health."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5789857","DOI":"10.1155\/2016\/5789857","article-title":"Positive modulation of pink Nelumbo nucifera flowers on memory impairment, brain damage, and biochemical profiles in restraint rats","volume":"2016","author":"Prabsattroo","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1002\/tox.24175","article-title":"Nelumbo nucifera leaves extract ameliorated scopolamine-induced cognition impairment via enhanced adult hippocampus neurogenesis","volume":"39","author":"Lee","year":"2024","journal-title":"Environ. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s11011-017-9963-x","article-title":"Phytochemical screening, acute toxicity, anxiolytic and antidepressant activities of the Nelumbo nucifera fruit","volume":"32","author":"Rajput","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chheng, C., Waiwut, P., Plekratoke, K., Chulikhit, Y., Daodee, S., Monthakantirat, O., Pitiporn, S., Musigavong, N., Kwankhao, P., and Boonyarat, C. (2020). Multitarget Activities of Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Against Alzheimer\u2032s Disease. Pharmaceuticals, 13.","DOI":"10.3390\/ph13050079"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1515\/znc-2020-0304","article-title":"Benzylisoquinoline alkaloids from Nelumbo nucifera Gaertn. petals with antiausterity activities against the HeLa human cervical cancer cell line","volume":"76","author":"Maneenet","year":"2021","journal-title":"Z. Naturforsch. C J. Biosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4103\/0973-1296.80666","article-title":"Isolation and identification of phenolic compounds from Gynura divaricata leaves","volume":"7","author":"Cao","year":"2011","journal-title":"Pharmacogn. Mag."},{"key":"ref_25","first-page":"241","article-title":"Polyphenolic compounds in Scopolia caucasica Kolesn. ex Kreyer (Solanaceae)","volume":"64","author":"Nowak","year":"2007","journal-title":"Acta Pol. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0031-9422(02)00486-7","article-title":"Malonylated flavonol glycosides from the petals of Clitoria ternatea","volume":"62","author":"Kazuma","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_27","first-page":"70","article-title":"Identification of water-soluble components, that are not saponins, from Dioscorea nipponica Mak","volume":"2","author":"Zhang","year":"2007","journal-title":"Asian J. Tradit. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100","DOI":"10.31254\/phyto.2016.5302","article-title":"Isolation and identification of euphol and \u03b2-sitosterol from the dichloromethane extracts of Synadenium glaucescens","volume":"5","author":"Nyigo","year":"2016","journal-title":"J. Phytopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Khamphukdee, C., Monthakantirat, O., Chulikhit, Y., Buttachon, S., Lee, M., Silva, A., Sekeroglu, N., and Kijjoa, A. (2018). Chemical constituents and antidepressant-like effects in ovariectomized mice of the ethanol extract of Alternanthera philoxeroides. Molecules, 23.","DOI":"10.3390\/molecules23092202"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jep.2014.08.014","article-title":"Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action","volume":"156","author":"Mizuki","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Daodee, S., Monthakantirat, O., Tantipongpiradet, A., Maneenet, J., Chotritthirong, Y., Boonyarat, C., Khamphukdee, C., Kwankhao, P., Pitiporn, S., and Awale, S. (2022). Effect of Yakae-Prajamduen-Jamod traditional Thai remedy on cognitive impairment in an ovariectomized mouse model and its mechanism of action. Molecules, 27.","DOI":"10.3390\/molecules27134310"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00428203","article-title":"The Tail suspension test: A new method for screening antidepressants in mice","volume":"85","author":"Steru","year":"1985","journal-title":"Psychopharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0014-2999(78)90414-4","article-title":"\u201cBehavioural despair\u201d in rats and mice: Strain differences and the effects of imipramine","volume":"51","author":"Porsolt","year":"1978","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Daodee, S., Monthakantirat, O., Ruengwinitwong, K., Gatenakorn, K., Maneenet, J., Khamphukdee, C., Sekeroglu, N., Chulikhit, Y., and Kijjoa, A. (2019). Effects of the ethanol extract of Dipterocarpus alatus leaf on the unpredictable chronic mild stress-induced depression in ICR mice and its possible mechanism of action. Molecules, 24.","DOI":"10.3390\/molecules24183396"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ayaz, M., Junaid, M., Ullah, F., Subhan, F., Sadiq, A., Ali, G., Ovais, M., Shahid, M., Ahmad, A., and Wadood, A. (2017). Anti-Alzheimer\u2019s studies on \u03b2-Sitosterol isolated from Polygonum hydropiper L. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00697"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5762172","DOI":"10.1155\/2017\/5762172","article-title":"Antidepressant flavonoids and their relationship with oxidative stress","volume":"2017","author":"Hritcu","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Herraiz, T., and Guill\u00e9n, H. (2018). Monoamine oxidase-A inhibition and associated antioxidant activity in plant extracts with potential antidepressant actions. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/4810394"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ynstr.2016.08.002","article-title":"The chronic mild stress (CMS) model of depression: History, evaluation and usage","volume":"6","author":"Willner","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1146\/annurev-clinpsy-050212-185606","article-title":"Depression, stress, and anhedonia: Toward a synthesis and integrated model","volume":"10","author":"Pizzagalli","year":"2014","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_41","first-page":"1","article-title":"Rodent models of depression: Forced swim and tail suspension behavioral despair tests in rats and mice","volume":"55","author":"Moser","year":"2011","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.physbeh.2013.05.012","article-title":"Factors influencing behavior in the forced swim test","volume":"118","author":"Bogdanova","year":"2013","journal-title":"Physiol. Behav."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Maneenet, J., Daodee, S., Monthakantirat, O., Boonyarat, C., Khamphukdee, C., Kwankhao, P., Pitiporn, S., Awale, S., Chulikhit, Y., and Kijjoa, A. (2019). Kleeb Bua Daeng, a Thai traditional herbal formula, ameliorated unpredictable chronic mild stress-induced cognitive impairment in ICR mice. Molecules, 24.","DOI":"10.3390\/molecules24244587"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbi.2020.12.033","article-title":"Stress impairs response to antidepressants via HPA axis and immune system activation","volume":"93","author":"Menke","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nature10287","article-title":"Adult hippocampal neurogenesis buffers stress responses and depressive behaviour","volume":"476","author":"Snyder","year":"2011","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Saeedi, M., and Rashidy-Pour, A. (2021). Association between chronic stress and Alzheimer\u2032s disease: Therapeutic effects of Saffron. Biomed. Pharmacother., 133.","DOI":"10.1016\/j.biopha.2020.110995"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7840","DOI":"10.1523\/JNEUROSCI.0730-11.2011","article-title":"Stress acts cumulatively to precipitate Alzheimer\u2032s disease-like tau pathology and cognitive deficits","volume":"31","author":"Sotiropoulos","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Laine, M.A., and Shansky, R.M. (2022). Rodent models of stress and dendritic plasticity-Implications for psychopathology. Neurobiol. Stress, 17.","DOI":"10.1016\/j.ynstr.2022.100438"},{"key":"ref_49","first-page":"237","article-title":"BDNF function and intracellular signaling in neurons","volume":"25","author":"Numakawa","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhang, S.Q., Cao, L.L., Liang, Y.Y., and Wang, P. (2021). The molecular mechanism of chronic high-dose corticosterone-induced aggravation of cognitive impairment in APP\/PS1 transgenic mice. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.613421"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1080\/10520295.2017.1323276","article-title":"The antidepressant-like effect of Ocimum basilicum in an animal model of depression","volume":"92","author":"Ali","year":"2017","journal-title":"Biotech. Histochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7260130","DOI":"10.1155\/2017\/7260130","article-title":"Brain-derived neurotrophic factor, depression, and physical activity: Making the neuroplastic connection","volume":"2017","author":"Phillips","year":"2017","journal-title":"Neural Plast."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0896-6273(00)80395-5","article-title":"CREB: A major mediator of neuronal neurotrophin responses","volume":"19","author":"Finkbeiner","year":"1997","journal-title":"Neuron"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/BF02704114","article-title":"Cyclic AMP response element binding protein and brain-derived neurotrophic factor: Molecules that modulate our mood?","volume":"31","author":"Nair","year":"2006","journal-title":"J. Biosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"385","DOI":"10.31887\/DCNS.2008.10.4\/gracagni","article-title":"Cellular and Molecular mechanisms in the long-term action of antidepressants","volume":"10","author":"Racagni","year":"2008","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.brainres.2006.09.009","article-title":"Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB","volume":"1122","author":"Xu","year":"2006","journal-title":"Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.pneurobio.2005.06.003","article-title":"BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis","volume":"76","author":"Bramham","year":"2005","journal-title":"Prog. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.addr.2008.06.002","article-title":"Monoamine oxidase inactivation: From pathophysiology to therapeutics","volume":"60","author":"Bortolato","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.pnpbp.2016.02.012","article-title":"Drugs related to monoamine oxidase activity","volume":"69","year":"2016","journal-title":"Prog. Neuro Psychopharmacol. Biol. Psychiatry"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/1\/94\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:56:01Z","timestamp":1760115361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/1\/94"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,29]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["nu17010094"],"URL":"https:\/\/doi.org\/10.3390\/nu17010094","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,29]]}}}