{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:26:48Z","timestamp":1780082808298,"version":"3.54.0"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFD1600303"],"award-info":[{"award-number":["2022YFD1600303"]}]},{"name":"Agricultural Science and Technology Innovation Program, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic stress disrupts neuroendocrine regulation, neurotransmitter balance, and neuronal redox homeostasis, thereby contributing to the development of anxiety-related neuropathology. Arecoline, the predominant alkaloid of Areca catechu L., displays diverse neuropharmacological properties, yet its role in stress-induced emotional dysfunction has not been fully elucidated. This study examined the anxiolytic-like and neuroprotective effects of arecoline in mice exposed to chronic unpredictable mild stress (CUMS). Arecoline administration markedly improved behavioral outcomes, reflected by increased central exploration in the open-field test, prolonged time in the light compartment, and enhanced open-arm activity in the elevated plus maze. These behavioral benefits were accompanied by normalization of serum corticosterone levels, restoration of hippocampal neurotransmitters, reinforcement of antioxidant enzyme activities, and attenuation of pro-inflammatory cytokines. At the molecular level, arecoline elevated brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), cAMP response element-binding protein (CREB), N-methyl-D-aspartate receptor (NMDAR), and Ca2+\/calmodulin-dependent protein kinase II (CaMKII), indicating enhanced synaptic plasticity, while concurrently diminishing oxidative and inflammatory stress. Collectively, the findings suggest that arecoline exerts multifaceted neuroprotective actions under chronic stress by coordinating neuroendocrine modulation, neurotransmitter homeostasis, antioxidant defenses, and synaptic plasticity. This study provides new mechanistic evidence supporting the potential relevance of arecoline as a functional neuroactive compound for managing stress-induced anxiety disorders.<\/jats:p>","DOI":"10.3390\/ijms27010371","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuromodulatory Effects of Arecoline on Anxiety-like Behavior in Mice Exposed to Chronic Unpredictable Mild Stress"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiangfei","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"},{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.31887\/DCNS.2015.17.3\/bbandelow","article-title":"Epidemiology of anxiety disorders in the 21st century","volume":"17","author":"Bandelow","year":"2015","journal-title":"Dialogues Clin. 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