{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:41:44Z","timestamp":1791549704374,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T00:00:00Z","timestamp":1608940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004486","name":"Fondazione Cassa di Risparmio di Perugia","doi-asserted-by":"publisher","award":["Project 2019.0321.026"],"award-info":[{"award-number":["Project 2019.0321.026"]}],"id":[{"id":"10.13039\/501100004486","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009889","name":"Regione Umbria","doi-asserted-by":"publisher","award":["PO FSE Umbria 2014-2020 - Asse 3"],"award-info":[{"award-number":["PO FSE Umbria 2014-2020 - Asse 3"]}],"id":[{"id":"10.13039\/501100009889","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Muscle atrophy, i.e., the loss of skeletal muscle mass and function, is an unresolved problem associated with aging (sarcopenia) and several pathological conditions. The imbalance between myofibrillary protein breakdown (especially the adult isoforms of myosin heavy chain, MyHC) and synthesis, and the reduction of muscle regenerative potential are main causes of muscle atrophy. Methods: Starting from one-hundred dried hydroalcoholic extracts of medical plants, we identified those able to contrast the reduction of C2C12 myotube diameter in well-characterized in vitro models mimicking muscle atrophy associated to inflammatory states, glucocorticoid treatment or nutrient deprivation. Based on their ability to rescue type II MyHC (MyHC-II) expression in atrophying conditions, six extracts with different phytochemical profiles were selected, mixed in groups of three, and tested on atrophic myotubes. The molecular mechanism underpinning the effects of the most efficacious formulation, and its efficacy on myotubes obtained from muscle biopsies of young and sarcopenic subjects were also investigated. Results: We identified WST (Withania somnifera, Silybum marianum, Trigonella foenum-graecum) formulation as extremely efficacious in protecting C2C12 myotubes against MyHC-II degradation by stimulating Akt (protein kinase B)-dependent protein synthesis and p38 MAPK (p38 mitogen-activated protein kinase)\/myogenin-dependent myoblast differentiation. WST sustains trophism in C2C12 and young myotubes, and rescues the size, developmental MyHC expression and myoblast fusion in sarcopenic myotubes. Conclusion: WST strongly counteracts muscle atrophy associated to different conditions in vitro. The future validation in vivo of our results might lead to the use of WST as a food supplement to sustain muscle mass in diffuse atrophying conditions, and to reverse the age-related functional decline of human muscles, thus improving people quality of life and reducing social and health-care costs.<\/jats:p>","DOI":"10.3390\/nu13010049","type":"journal-article","created":{"date-parts":[[2020,12,27]],"date-time":"2020-12-27T20:04:58Z","timestamp":1609099498000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification of Withania somnifera-Silybum marianum-Trigonella foenum-graecum Formulation as a Nutritional Supplement to Contrast Muscle Atrophy and Sarcopenia"],"prefix":"10.3390","volume":"13","author":[{"given":"Laura","family":"Salvadori","sequence":"first","affiliation":[{"name":"Department Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0541-390X","authenticated-orcid":false,"given":"Manuela","family":"Mandrone","sequence":"additional","affiliation":[{"name":"Department Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Manenti","sequence":"additional","affiliation":[{"name":"Biokyma srl Laboratories, 52031 Anghiari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia","family":"Ercolani","sequence":"additional","affiliation":[{"name":"Biokyma srl Laboratories, 52031 Anghiari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cornioli","sequence":"additional","affiliation":[{"name":"Biokyma srl Laboratories, 52031 Anghiari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-4558","authenticated-orcid":false,"given":"Mariacaterina","family":"Lianza","sequence":"additional","affiliation":[{"name":"Department Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Tomasi","sequence":"additional","affiliation":[{"name":"Department Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Chiappalupi","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9531-7788","authenticated-orcid":false,"given":"Ester Sara","family":"Di Filippo","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department Neuroscience, Imaging and Clinical Sciences, University G. D\u2019Annunzio Chieti e Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4557-9127","authenticated-orcid":false,"given":"Stefania","family":"Fulle","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department Neuroscience, Imaging and Clinical Sciences, University G. D\u2019Annunzio Chieti e Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Poli","sequence":"additional","affiliation":[{"name":"Department Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-9679","authenticated-orcid":false,"given":"Guglielmo","family":"Sorci","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-3379","authenticated-orcid":false,"given":"Francesca","family":"Riuzzi","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1242\/dmm.010389","article-title":"Cellular and molecular mechanisms of muscle atrophy","volume":"6","author":"Bonaldo","year":"2013","journal-title":"Dis. 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Care"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/1\/49\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:46:22Z","timestamp":1760179582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/1\/49"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,26]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["nu13010049"],"URL":"https:\/\/doi.org\/10.3390\/nu13010049","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,26]]}}}