{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:50:29Z","timestamp":1788292229933,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"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":["2023YFD2201304"],"award-info":[{"award-number":["2023YFD2201304"]}]},{"name":"National Key Research and Development Program of China","award":["YYLH05"],"award-info":[{"award-number":["YYLH05"]}]},{"name":"National Key Research and Development Program of China","award":["YBXM2417"],"award-info":[{"award-number":["YBXM2417"]}]},{"name":"Nanfan special project of the Chinese Academy of Agricultural Sciences","award":["2023YFD2201304"],"award-info":[{"award-number":["2023YFD2201304"]}]},{"name":"Nanfan special project of the Chinese Academy of Agricultural Sciences","award":["YYLH05"],"award-info":[{"award-number":["YYLH05"]}]},{"name":"Nanfan special project of the Chinese Academy of Agricultural Sciences","award":["YBXM2417"],"award-info":[{"award-number":["YBXM2417"]}]},{"name":"Nanfan special project of CAAS","award":["2023YFD2201304"],"award-info":[{"award-number":["2023YFD2201304"]}]},{"name":"Nanfan special project of CAAS","award":["YYLH05"],"award-info":[{"award-number":["YYLH05"]}]},{"name":"Nanfan special project of CAAS","award":["YBXM2417"],"award-info":[{"award-number":["YBXM2417"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The betel nut is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. Arecoline is an active ingredient from the areca nut. It has many pharmacological effects and can affect the central nervous system. In this study, we found that arecoline can relieve fatigue behavior. Objective: This research aims to estimate the anti-fatigue effects of arecoline and explore its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL\/6 mice were randomly assigned to six groups: a control group, an SD-induced fatigue model group, a group that received Rhodiola Rosea capsules (2.5 mg\/kg), and three arecoline groups, which were administered at low, medium, and high doses (10, 20, and 40 mg\/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on mouse fatigue-related behaviors were assessed by behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. The release levels of the related biochemical markers were measured by enzyme-linked immunosorbent assays (ELISAs). Western blotting was employed to quantify the expression levels of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline obviously decreased both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased the contents of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol in the serum, while it elevated the levels of total testosterone, lactate dehydrogenase, and immunoglobulin G. Furthermore, it significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels showed significant increases, cytokine levels were markedly reduced, and the expressions of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissues were significantly upregulated. Conclusions: This study demonstrates that arecoline has anti-fatigue activity, and the specific mechanisms are associated with elevating glucose and lipid metabolism levels, relieving oxidative stress damage, inhibiting neuroinflammatory response, and regulating neurotransmitter levels and the Keap1\/Nrf2\/HO-1 signaling pathway. The research provides a new direction for arecoline\u2019s potential in preventing and improving fatigue.<\/jats:p>","DOI":"10.3390\/nu16162783","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T04:26:57Z","timestamp":1724300817000},"page":"2783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Research on the Anti-Fatigue Effects and Mechanisms of Arecoline in Sleep-Deprived Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Danyang","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiameng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-7093","authenticated-orcid":false,"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, 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 (CAAS), Beijing 100193, 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 (CAAS), Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"},{"name":"National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, 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 (CAAS), Beijing 100193, China"},{"name":"College of Food Science and Engineering, Shanxi Agricultural University, Jinzhong 030801, China"},{"name":"National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya 572024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1177\/1099800418764326","article-title":"A Systematic Review of Biological Mechanisms of Fatigue in Chronic Illness","volume":"20","author":"Matura","year":"2018","journal-title":"Biol. 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