{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:03:08Z","timestamp":1789585388233,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondi di Ateneo, UCSC Rome, Italy","award":["R4124500660"],"award-info":[{"award-number":["R4124500660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Muscle weakness and muscle loss characterize many physio-pathological conditions, including sarcopenia and many forms of muscular dystrophy, which are often also associated with mitochondrial dysfunction. Verbascoside, a phenylethanoid glycoside of plant origin, also named acteoside, has shown strong antioxidant and anti-fatigue activity in different animal models, but the molecular mechanisms underlying these effects are not completely understood. This study aimed to investigate the influence of verbascoside on mitochondrial function and its protective role against H2O2-induced oxidative damage in murine C2C12 myoblasts and myotubes pre-treated with verbascoside for 24 h and exposed to H2O2. We examined the effects of verbascoside on cell viability, intracellular reactive oxygen species (ROS) production and mitochondrial function through high-resolution respirometry. Moreover, we verified whether verbascoside was able to stimulate nuclear factor erythroid 2-related factor (Nrf2) activity through Western blotting and confocal fluorescence microscopy, and to modulate the transcription of its target genes, such as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1\u03b1), by Real Time PCR. We found that verbascoside (1) improved mitochondrial function by increasing mitochondrial spare respiratory capacity; (2) mitigated the decrease in cell viability induced by H2O2 and reduced ROS levels; (3) promoted the phosphorylation of Nrf2 and its nuclear translocation; (4) increased the transcription levels of HO-1 and, in myoblasts but not in myotubes, those of PGC-1\u03b1. These findings contribute to explaining verbascoside\u2019s ability to relieve muscular fatigue and could have positive repercussions for the development of therapies aimed at counteracting muscle weakness and mitochondrial dysfunction.<\/jats:p>","DOI":"10.3390\/ijms242015276","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T10:43:10Z","timestamp":1697539390000},"page":"15276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Verbascoside Elicits Its Beneficial Effects by Enhancing Mitochondrial Spare Respiratory Capacity and the Nrf2\/HO-1 Mediated Antioxidant System in a Murine Skeletal Muscle Cell Line"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2123-1516","authenticated-orcid":false,"given":"Francesca","family":"Sciandra","sequence":"first","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche \u201cGiulio Natta\u201d\u2014SCITEC Sede di Roma, Largo F. Vito, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-8903","authenticated-orcid":false,"given":"Patrizia","family":"Bottoni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Sezione di Biochimica, Universit\u00e0 Cattolica del Sacro Cuore di Roma, Largo F. Vito 1, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5544-8457","authenticated-orcid":false,"given":"Marinella","family":"De Leo","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, Via Bonanno 33, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-0448","authenticated-orcid":false,"given":"Alessandra","family":"Braca","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, Via Bonanno 33, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-8826","authenticated-orcid":false,"given":"Andrea","family":"Brancaccio","sequence":"additional","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche \u201cGiulio Natta\u201d\u2014SCITEC Sede di Roma, Largo F. Vito, 00168 Roma, Italy"},{"name":"School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Bozzi","sequence":"additional","affiliation":[{"name":"Istituto di Scienze e Tecnologie Chimiche \u201cGiulio Natta\u201d\u2014SCITEC Sede di Roma, Largo F. Vito, 00168 Roma, Italy"},{"name":"Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Sezione di Biochimica, Universit\u00e0 Cattolica del Sacro Cuore di Roma, Largo F. Vito 1, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"982794","DOI":"10.1155\/2012\/982794","article-title":"Reactive oxygen species in skeletal muscle signalling","volume":"2012","author":"Barbieri","year":"2012","journal-title":"J. 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