{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:59:48Z","timestamp":1788850788429,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Propolis, a natural mixture rich in bioactive compounds, has shown the potential to relieve exercise-induced fatigue. However, the underlying mechanism remains unclear. This study aimed to explore the anti-fatigue effects of ethanol extract of propolis (EEP) and its potential mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male C57BL\/6 mice aged 6\u20138\u202fweeks were subjected to swim training with or without EEP supplementation (400\u202fmg\/kg.bw) for 3\u202fweeks, followed by a exhaustive swimming test to simulate exercise-induced fatigue. The exhaustion time and fatigue-related biochemical indices were measured to assess the anti-fatigue effects. The anti-fatigue mechanism of EEP was further investigated using untargeted serum metabolomics and 16S rRNA gene sequencing of the gut microbiota.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results showed that supplementation with EEP significantly increased the exhaustive swimming time of the mice by 27.64%, with no significant effects on body weight, food intake, or viscera and muscle index among the 3 groups. Biochemical analysis indicated that EEP effectively alleviated fatigue-related biochemical indices caused by excessive exercise, including liver glycogen (LG), muscle glycogen (MG), blood lactate (BLA), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), interleukin-6 (IL-6), interleukin-1\u03b2 (IL-1\u03b2), tumor necrosis factor-alpha (TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      ), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA). Serum metabolomics analysis revealed that EEP reversed the levels of 6 key metabolites (Gamma-Aminobutyric acid, pipecolic acid, L-isoleucine, sucrose, succinic acid, and L-carnitine), which are involved in 7 metabolic pathways related to energy metabolism, amino acid metabolism, and carbohydrate metabolism. 16S rRNA sequencing analysis of the cecal contents showed that EEP altered the composition and structure of the gut microbiota, increasing the abundance of butyrate-producing bacteria and reducing the abundance of harmful bacteria. Correlation analysis revealed that specific bacterial genera were closely related to certain differential metabolites and biochemical indices.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study showed that EEP significantly increased exercise endurance in mice and exerted anti-fatigue effects by modulating key metabolites and the gut microbiota.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2025.1549913","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T10:23:33Z","timestamp":1742984613000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Ethanol extract of propolis relieves exercise-induced fatigue via modulating the metabolites and gut microbiota in mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Shan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"102360","DOI":"10.1016\/j.fbio.2023.102360","article-title":"Natural bioactive flavonoids as promising agents in alleviating exercise-induced fatigue","volume":"51","author":"Liu","year":"2023","journal-title":"Food Biosci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"913367","DOI":"10.3389\/fphar.2022.913367","article-title":"Trilobatin, a naturally occurring food additive, ameliorates exhaustive exercise-induced fatigue in mice: involvement of Nrf2\/ARE\/Ferroptosis signaling pathway","volume":"13","author":"Xiao","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"105846","DOI":"10.1016\/j.jff.2023.105846","article-title":"Anti-fatigue effects and mechanism of Syngnathus schlegeli peptides supplementation on exercise-fatigued mice","volume":"110","author":"Cai","year":"2023","journal-title":"J Funct Foods"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"3456","DOI":"10.1002\/jsfa.11693","article-title":"The anti-fatigue activity of corn peptides and their effect on gut bacteria","volume":"102","author":"Feng","year":"2022","journal-title":"J Sci Food Agric"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"10359","DOI":"10.3390\/ijms251910359","article-title":"The antioxidant and anti-fatigue effects of rare Ginsenosides and \u03b3-aminobutyric acid in fermented ginseng and germinated Brown Rice puree","volume":"25","author":"Feng","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1004174","DOI":"10.3389\/fnut.2022.1004174","article-title":"Deciphering the potential role of Maca compounds prescription influencing gut microbiota in the management of exercise-induced fatigue by integrative genomic analysis","volume":"9","author":"Zhu","year":"2022","journal-title":"Front Nutr"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"11097","DOI":"10.1039\/D2FO02308C","article-title":"An integrated network pharmacology and metabolomics approach to reveal the immunomodulatory mechanism of Brassica rapa L. 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