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Thailand traditionally uses Tri-Kaysorn-Mas (TKM), a blend of three medicinal herbs, as a tonic to stimulate appetite and relieve dyspepsia. Due to its antioxidant and anti-acetylcholinesterase activities, we investigated the effects of TKM (50 and 100 mg\/kg\/day, p.o., for 8 weeks) on cognitive deficits and their underlying causes in an ovariectomized (OVX) mouse model of menopause. OVX mice showed cognitive impairment in the Y-maze, novel object recognition task (NORT), and Morris water maze (MWM) behavioral tests, along with atrophic changes to the uterus, altered levels of serum 17\u03b2-estradiol, and down-regulated expression of estrogen receptors (ER\u03b1 and ER\u03b2). These behavioral effects were reversed by TKM. TKM decreased malondialdehyde (MDA) levels and mitigated oxidative stress in the brain by enhancing the activity of superoxide dismutase (SOD) and catalase (CAT) and by up-regulating the antioxidant-related gene Nrf2 while down-regulating Keap1. TKM also counteracted OVX-induced neurodegeneration by enhancing the expression of the neurogenesis-related genes BDNF and CREB. The results indicate that TKM extract alleviates oxidative brain damage and neurodegeneration while enhancing cognitive behavior in OVX mice, significantly improving cognitive deficiencies related to menopause\/ovariectomy through multiple targets.<\/jats:p>","DOI":"10.3390\/ph17091182","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T03:04:18Z","timestamp":1725851058000},"page":"1182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effectiveness of Tri-Kaysorn-Mas Extract in Ameliorating Cognitive-like Behavior Deficits in Ovariectomized Mice via Activation of Multiple Mechanisms"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-5441","authenticated-orcid":false,"given":"Abdulwaris","family":"Mading","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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"},{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4065-6090","authenticated-orcid":false,"given":"Chantana","family":"Boonyarat","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanida","family":"Sukketsiri","sequence":"additional","affiliation":[{"name":"Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-4349","authenticated-orcid":false,"given":"Pakakrong","family":"Kwankhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Chao Phya Abhaibhubejhr Hospital, Ministry of Public Health, Prachinburi 25000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supaporn","family":"Pitiporn","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Chao Phya Abhaibhubejhr Hospital, Ministry of Public Health, Prachinburi 25000, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.5498\/wjp.v11.i8.412","article-title":"Menopause and Cognitive Impairment: A Narrative Review of Current Knowledge","volume":"11","author":"Conde","year":"2021","journal-title":"WJP"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101205","DOI":"10.1016\/j.smrv.2019.07.008","article-title":"Insomnia and Cognitive Performance: A Systematic Review and Meta-Analysis","volume":"48","author":"Slavish","year":"2019","journal-title":"Sleep Med. 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