{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:12:20Z","timestamp":1789517540160,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T00:00:00Z","timestamp":1655510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Behavioral Sciences"],"abstract":"<jats:p>Depression is the most common behavior disorder that leads to many disabilities. The main aim of this study was to evaluate the effects of a Polygonum minus (P. minus) aqueous extract on chronic ultra-mild stress (CUMS)-induced depressive mice model. Chronic ultra-mild stress can disturb the neurotransmitters levels and plasticity of the hippocampus. Balb\/c male mice were used in this study, which consisted of six groups (n = 14). Treatment was given for eight weeks, and chronic ultra-mild stress was applied for six weeks. Commercially available P. minus extract (BioKesum\u00ae) was used in this study. The behavior and neurochemical parameters were investigated through behavioral Tests and ELISA assays. P. minus administration significantly (p &lt; 0.05) restored CUMS-induced behavior abnormalities, decreased the immobility time, and increased the sucrose preference and increased the spatial memory. P. minus treatment also showed the decreased level of serum corticosterone and increased the level of hippocampal neurotransmitters (Serotonin and Norepinephrine) significantly (p &lt; 0.05). The brain-derived neurotrophic factor (BDNF) level also increased significantly in both the prefrontal cortex and hippocampus (p &lt; 0.05). P. minus treatment exhibited significant (p &lt; 0.05) reduction of Monoamine Oxidase-A (MAO-A) in the hippocampus. These findings indicate that P. minus aqueous extract exhibits antidepressant effects, including decreased immobility time, increased spatial memory, reduced corticosterone, increased BDNF level, and reduced MAO-A enzyme level with increasing the monoamines (serotonin and norepinephrine) in the hippocampus.<\/jats:p>","DOI":"10.3390\/bs12060196","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T09:51:11Z","timestamp":1655545871000},"page":"196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Antidepressant-like Effects of Polygonum minus Aqueous Extract in Chronic Ultra-Mild Stress-Induced Depressive Mice Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Muhammad Irfan","family":"Bashir","sequence":"first","affiliation":[{"name":"Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Hidayah Kaz","family":"Abdul Aziz","sequence":"additional","affiliation":[{"name":"Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dzul Azri Mohamed","family":"Noor","sequence":"additional","affiliation":[{"name":"Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e027530","DOI":"10.1136\/bmjopen-2018-027530","article-title":"Association between Area Deprivation and Major Depressive Disorder in British Men and Women: A Cohort Study","volume":"9","author":"Remes","year":"2019","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1038\/s41380-019-0486-1","article-title":"Association between Major Depressive Disorder and Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomisation Study in the UK Biobank","volume":"25","author":"Mulugeta","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1080\/13651501.2020.1757116","article-title":"Duration of Untreated Illness and Depression Severity Are Associated with Cognitive Impairment in Mood Disorders","volume":"24","author":"Galimberti","year":"2020","journal-title":"Int. J. Psychiatry Clin. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jpsychires.2020.12.069","article-title":"Association among Early Life Stress, Mood Features, Hopelessness and Suicidal Risk in Bipolar Disorder: The Potential Contribution of Insomnia Symptoms","volume":"135","author":"Palagini","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S2215-0366(20)30036-5","article-title":"Treatment Outcomes for Depression: Challenges and Opportunities","volume":"7","author":"Cuijpers","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Govindarajulu, M., Shankar, T., Patel, S., Fabbrini, M., Manohar, A., Ramesh, S., Boralingaiah, P., Sharma, S., Clark, R.C., and Deruiter, J. (2021). Reserpine-Induced Depression and Other Neurotoxicity: A Monoaminergic Hypothesis. Medicinal Herbs and Fungi, Springer.","DOI":"10.1007\/978-981-33-4141-8_12"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1007\/s00213-020-05585-x","article-title":"Mechanisms Underlying Remediation of Depression-Associated Anxiety by Chronic N-Acetyl Cysteine Treatment","volume":"237","author":"Chakraborty","year":"2020","journal-title":"Psychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pourhamzeh, M., Moravej, F.G., Arabi, M., Shahriari, E., Mehrabi, S., Ward, R., Ahadi, R., and Joghataei, M.T. (2021). The Roles of Serotonin in Neuropsychiatric Disorders. Cell. Mol. Neurobiol., 1\u201322.","DOI":"10.1007\/s10571-021-01064-9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/164_2020_384","article-title":"Monoamine Oxidase Inhibitors: From Classic to New Clinical Approaches","volume":"Volume 264","author":"Duarte","year":"2020","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.18596\/jotcsa.823874","article-title":"Monoamine Oxidase Inhibitory Effects of Medicinal Plants in Management of Alzheimer\u2019s Disease","volume":"8","author":"Ege","year":"2021","journal-title":"J. Turk. Chem. Soc. Sect. A Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, J., Cheng, C., Xin, C., and Wang, Z. (2019). The Antidepressant-like Effect of Flavonoids from Trigonella Foenum-Graecum Seeds in Chronic Restraint Stress Mice via Modulation of Monoamine Regulatory Pathways. Molecules, 24.","DOI":"10.3390\/molecules24061105"},{"key":"ref_12","first-page":"17","article-title":"Flavonoid Derivatives for Monoamine Oxidase\u2013A Inhibition","volume":"1","author":"Esfahani","year":"2019","journal-title":"Adv. J. Chem.-Sect. B Nat. Prod. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1176\/appi.ajp.2019.19070720","article-title":"Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression","volume":"177","author":"Cole","year":"2020","journal-title":"Am. J. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112439","DOI":"10.1016\/j.bbr.2019.112439","article-title":"Antidepressant-like Effects of \u03b2-Caryophyllene on Restraint plus Stress-Induced Depression","volume":"380","author":"Hwang","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/FBP.0000000000000431","article-title":"Validation of Chronic Mild Stress in the Wistar-Kyoto Rat as an Animal Model of Treatment-Resistant Depression","volume":"30","author":"Willner","year":"2019","journal-title":"Behav. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/cbin.11123","article-title":"Progesterone and Fluoxetine Treatments of Postpartum Depressive-like Behavior in Rat Model","volume":"43","author":"Hu","year":"2019","journal-title":"Cell Biol. Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Khan, A.R., Geiger, L., Wiborg, O., and Cz\u00e9h, B. (2020). Stress-Induced Morphological, Cellular and Molecular Changes in the Brain\u2014Lessons Learned from the Chronic Mild Stress Model of Depression. Cells, 9.","DOI":"10.3390\/cells9041026"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e485","DOI":"10.1038\/tp.2014.125","article-title":"Hippocampal and Behavioral Dysfunctions in a Mouse Model of Environmental Stress: Normalization by Agomelatine","volume":"4","author":"Boulle","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/0974-8490.147125","article-title":"Review on Polygonum Minus. Huds, a Commonly Used Food Additive in Southeast Asia","volume":"7","author":"Christapher","year":"2015","journal-title":"Pharmacogn. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"George, A., Ng, C.P., O\u2019Callaghan, M., Jensen, G.S., and Wong, H.J. (2014). In Vitro and Ex-Vivo Cellular Antioxidant Protection and Cognitive Enhancing Effects of an Extract of Polygonum Minus Huds (LineminusTM) Demonstrated in a Barnes Maze Animal Model for Memory and Learning. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-161"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lau, H., Shahar, S., Mohamad, M., Rajab, N.F., Yahya, H.M., Din, N.C., and Hamid, H.A. (2020). The Effects of Six Months Persicaria Minor Extract Supplement among Older Adults with Mild Cognitive Impairment: A Double-Blinded, Randomized, and Placebo-Controlled Trial. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-03092-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102504","DOI":"10.1016\/j.isci.2021.102504","article-title":"Gene-Environment Interactions Mediate Stress Susceptibility and Resilience through the CaMKII\u03b2\/TARP\u03b3-8\/AMPAR Pathway","volume":"24","author":"Sakai","year":"2021","journal-title":"iScience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jpsychires.2012.10.018","article-title":"Antidepressant-like Effect of Trans-Resveratrol in Chronic Stress Model: Behavioral and Neurochemical Evidences","volume":"47","author":"Yu","year":"2013","journal-title":"J. Psychiatr. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/10253890.2018.1438405","article-title":"Exploratory Rearing: A Context- and Stress-Sensitive Behavior Recorded in the Open-Field Test","volume":"21","author":"Sturman","year":"2018","journal-title":"Stress"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4939-8994-2_9","article-title":"The Open Field Test for Measuring Locomotor Activity and Anxiety-Like Behavior","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.6026\/97320630015172","article-title":"Effect of Salvia Officinalis L. and Rosmarinus Officinalis L. Leaves Extracts on Anxiety and Neural Activity","volume":"15","author":"Choukairi","year":"2019","journal-title":"Bioinformation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2744","DOI":"10.21769\/BioProtoc.2744","article-title":"Barnes Maze Procedure for Spatial Learning and Memory in Mice","volume":"8","author":"Pitts","year":"2018","journal-title":"Bio-Protocol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41398-018-0101-2","article-title":"Targeting Glucocorticoid Receptors Prevents the Effects of Early Life Stress on Amyloid Pathology and Cognitive Performance in APP\/PS1 Mice","volume":"8","author":"Lesuis","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.pnpbp.2012.05.018","article-title":"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","volume":"39","author":"Chiba","year":"2012","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1055\/s-2003-45148","article-title":"In Vitro Studies Indicate That Miquelianin (Quercetin 3-O-\u03b2-D- Glucuronopyranoside) Is Able to Reach the CNS from the Small Intestine","volume":"69","author":"Juergenliemk","year":"2003","journal-title":"Planta Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1039\/C4FO00817K","article-title":"Enhancement of Flavonoid Ability to Cross the Blood\u2013Brain Barrier of Rats by Co-Administration with \u03b1-Tocopherol","volume":"6","author":"Ferri","year":"2015","journal-title":"Food Funct."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1021\/acschemneuro.1c00371","article-title":"Quercitrin Rapidly Alleviated Depression-like Behaviors in Lipopolysaccharide-Treated Mice: The Involvement of PI3K\/AKT\/NF-\u039aB Signaling Suppression and CREB\/BDNF Signaling Restoration in the Hippocampus","volume":"12","author":"Sun","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1055\/s-2000-11119","article-title":"Flavonoids from Hypericum Perforatum Show Antidepressant Activity in the Forced Swimming Test","volume":"66","author":"Butterweck","year":"2000","journal-title":"Planta Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1055\/s-2006-951710","article-title":"Effects of St. John\u2019s Wort Extract and Single Constituents on Stress-Induced Hyperthermia in Mice","volume":"72","author":"Grundmann","year":"2006","journal-title":"Planta Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jep.2013.02.015","article-title":"Antidepressant-like Effect of Flavonoids Extracted from Apocynum Venetum Leaves on Brain Monoamine Levels and Dopaminergic System","volume":"147","author":"Zheng","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6530364","DOI":"10.1155\/2016\/6530364","article-title":"Involvement of 5-HT1A Receptors in the Anxiolytic-like Effects of Quercitrin and Evidence of the Involvement of the Monoaminergic System","volume":"2016","author":"Li","year":"2016","journal-title":"Evid.-Based Complement. Altern. Med."}],"container-title":["Behavioral Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-328X\/12\/6\/196\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:34:36Z","timestamp":1760139276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-328X\/12\/6\/196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,18]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["bs12060196"],"URL":"https:\/\/doi.org\/10.3390\/bs12060196","relation":{},"ISSN":["2076-328X"],"issn-type":[{"value":"2076-328X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,18]]}}}