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Given the critical role of oxidative stress and energy metabolism in exercise\u2010induced fatigue, we hypothesized that 18\u03b2\u2010GA could exert an ergogenic action by inhibiting excess reactive oxygen species (ROS) induction and promoting energy production in muscles. Mice were gavage\u2010fed with 18\u03b2\u2010GA for four consecutive days. Running ability was assessed based on the exhaustive treadmill test with high\u2010 and moderate\u2010intensity. Western blot analysis, enzyme\u2010linked immunosorbent assay, and immunofluorescence staining were used to measure the changes of muscle fatigue\u2010related markers, oxidative stress status, and energy metabolism in response to 18\u03b2\u2010GA exposure. Treatment with 18\u03b2\u2010GA significantly increased the exhaustive running distance (~37%) in the high\u2010intensity exercise, but not in the moderate\u2010intensity exercise. Mechanistically, reduction of oxidative stress and induction of antioxidants (SOD, CAT, and GSH) by 18\u03b2\u2010GA were observed. Moreover, 18\u03b2\u2010GA treatment caused an improved preservation of muscle glycogen (12%), which was associated with upregulation of glucose transporter 4 (GLUT4) (91%) and increased insulin level (17%). The findings of the present study clearly suggest that 18\u03b2\u2010GA holds excellent potential as a novel bioactive agent against high\u2010intensity exercise\u2010induced fatigue.<\/jats:p>","DOI":"10.1002\/ptr.7310","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T09:27:04Z","timestamp":1635413224000},"page":"6932-6943","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["18\u03b2\u2010glycyrrhetinic acid improves high\u2010intensity exercise performance by promoting glucose\u2010dependent energy production and inhibiting oxidative stress in mice"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9387-8776","authenticated-orcid":false,"given":"Xuan","family":"Ma","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixing","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-7370","authenticated-orcid":false,"given":"Shutao","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2780-5568","authenticated-orcid":false,"given":"Hongbo","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00421.2004"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070075"},{"issue":"6","key":"e_1_2_10_4_1","first-page":"709","article-title":"Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds","volume":"22","author":"Asl M. 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