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Isoliquiritigenin (ISL) is a promising extract known for its medical effects; however, its impact on muscle atrophy remains unclear. We investigated the effects of ISL on muscle atrophy both in vitro and in vivo. The results showed that 5\u2010\u00b5M ISL exhibited no significant cytotoxicity on C2C12 cells, as reflected by cell count kit\u20108 and 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine (EdU) tests. ISL increased the diameter of myotubes and downregulated forkhead box O proteins, muscle\u2010specific RING finger protein 1 (MuRF\u20101), and Atrogin\u20101 induced by Dexamethasone (Dex). ISL could also enhance the phosphorylation of Akt, the mammalian target of rapamycin (mTOR), eIF4E\u2010binding protein 1, and p70 S6 kinase in C2C12 myotubes. In animal experiments, ISL increased the muscle mass, improved the cross\u2010sectional area of muscles, and inhibited the expression of MuRF\u20101 and Atrogin\u20101 in muscle tissues. For physical performance, ISL enhanced grip strength and running endurance. ISL ameliorated Dex\u2010induced muscle atrophy both in vitro and in vivo, associated with increased diameter of myotubes and decreased Atrogin\u20101 and MuRF\u20101 expression via the Akt\/mTOR signaling pathway. This suggested that ISL could be used as a natural drug for muscle atrophy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.70000","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:20:13Z","timestamp":1740140413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Isoliquiritigenin, an Extract from Licorice, Attenuates Dexamethasone\u2010Induced Muscle Atrophy via Akt\/mTOR Pathway"],"prefix":"10.1002","volume":"69","author":[{"given":"Xin","family":"Jiao","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedic Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"School of Biomedical Engineering and Med\u2010X Research Institute Shanghai Jiao Tong University Shanghai China"},{"name":"Engineering Research Center of Digital Medicine and Clinical Translation 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