{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:14:30Z","timestamp":1791231270591,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C1003791"],"award-info":[{"award-number":["2020R1A2C1003791"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The effects of some drugs, aging, cancers, and other diseases can cause muscle wasting. Currently, there are no effective drugs for treating muscle wasting. In this study, the effects of ginsenoside Rd (GRd) on muscle wasting were studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tumour necrosis factor\u2010alpha (TNF\u2010\u03b1)\/interferon\u2010gamma (IFN\u2010\u03b3)\u2010induced myotube atrophy in mouse C2C12 and human skeletal myoblasts (HSkM) was evaluated based on cell thickness. Atrophy\u2010related signalling, reactive oxygen species (ROS) level, mitochondrial membrane potential, and mitochondrial number were assessed. GRd (10\u00a0mg\/kg body weight) was orally administered to aged mice (23\u201324\u00a0months old) and tumour\u2010bearing (Lewis lung carcinoma [LLC1] or CT26) mice for 5\u00a0weeks and 16\u00a0days, respectively. Body weight, grip strength, inverted hanging time, and muscle weight were assessed. Histological analysis was also performed to assess the effects of GRd. The evolutionary chemical binding similarity (ECBS) approach, molecular docking, Biacore assay, and signal transducer and activator of transcription (STAT) 3 reporter assay were used to identify targets of GRd.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GRd significantly induced hypertrophy in the C2C12 and HSkM myotubes (average diameter 50.8\u00a0\u00b1\u00a02.6% and 49.9%\u00a0\u00b1\u00a03.7% higher at 100\u00a0nM, vs. control, <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.001). GRd treatment ameliorated aging\u2010 and cancer\u2010induced (LLC1 or CT26) muscle atrophy in mice, which was evidenced by significant increases in grip strength, hanging time, muscle mass, and muscle tissue cross\u2010sectional area (1.3\u2010fold to 4.6\u2010fold, vs. vehicle, <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.01; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.001). STAT3 was found to be a possible target of GRd by the ECBS approach and molecular docking assay. Validation of direct interaction between GRd and STAT3 was confirmed through Biacore analysis. GRd also inhibited STAT3 phosphorylation and STAT3 reporter activity, which led to the inhibition of STAT3 nuclear translocation and the suppression of downstream targets of STAT3, such as atrogin\u20101, muscle\u2010specific RING finger protein (MuRF\u20101), and myostatin (MSTN) (29.0\u00a0\u00b1\u00a011.2% to 84.3\u00a0\u00b1\u00a030.5%, vs. vehicle, <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.01; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.001). Additionally, GRd scavenged ROS (91.7\u00a0\u00b1\u00a01.4% reduction at 1\u00a0nM, vs. vehicle, <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.001), inhibited TNF\u2010\u03b1\u2010induced dysregulation of ROS level, and improved mitochondrial integrity (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.01; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GRd ameliorates aging\u2010 and cancer\u2010induced muscle wasting. Our findings suggest that GRd may be a novel therapeutic agent or adjuvant for reversing muscle wasting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13084","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T21:00:20Z","timestamp":1663707620000},"page":"3149-3162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Ginsenoside Rd ameliorates muscle wasting by suppressing the signal transducer and activator of transcription 3 pathway"],"prefix":"10.1002","volume":"13","author":[{"given":"Yoseph Toni","family":"Wijaya","sequence":"first","affiliation":[{"name":"Department of Integrated Biomedical Science Soonchunhyang University  Cheonan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Setiawan","sequence":"additional","affiliation":[{"name":"Department of Integrated Biomedical Science Soonchunhyang University  Cheonan Republic of 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