{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:34:31Z","timestamp":1791466471065,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare, Republic of Korea","award":["HF23C0082"],"award-info":[{"award-number":["HF23C0082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Sarcopenia, a condition caused by an imbalance between muscle growth and loss, can severely affect the quality of life of elderly patients with metabolic, inflammatory, and cancer diseases. Vigeo, a nuruk-fermented extract of three plants (Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK)) has been reported to have anti-osteoporotic effects. However, evidence of the effects of Vigeo on muscle atrophy is not available. Here, in the in vivo model of dexamethasone (Dex)-induced muscle atrophy, Vigeo treatment significantly reversed Dex-induced decreases in calf muscle volume, gastrocnemius (GA) muscle weight, and histological cross-section area. In addition, in mRNA and protein analyses isolated from GA muscle, we observed that Vigeo significantly protected against Dex-induced mouse muscle atrophy by inhibiting protein degradation regulated by atrogin and MuRF-1. Moreover, we demonstrated that Vigeo significantly promoted C2C12 cell line differentiation, as evidenced by the increased width and length of myotubes, and the increased number of fused myotubes with three or more nuclei. Vigeo alleviated the formation of myotubes compared to the control group. Vigeo also significantly increased the mRNA and protein expression of myosin heavy chain (MyHC), MyoD, and myogenin compared to that in the control. Vigeo treatment significantly reduced the mRNA and protein expression of muscle degradation markers atrogin-1 and muscle RING Finger 1 (MuRF-1) in the C2C12 cell line in vitro. Vigeo also activated the AMP-activated protein kinase (AMPK)\/silent information regulator 1 (Sirt-1)\/peroxisome proliferator-activated receptor-\u03b3 co-activator-1\u03b1 (PGC1\u03b1) mitochondrial biogenesis pathway and the Akt\/mTOR protein synthesis signaling pathway in Dex-induced myotube atrophy. These findings suggest that Vigeo may have protective effects against Dex-induced muscle atrophy. Therefore, we propose Vigeo as a supplement or potential therapeutic agent to prevent or treat sarcopenia accompanied by muscle atrophy and degeneration.<\/jats:p>","DOI":"10.3390\/nu16162687","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T13:35:49Z","timestamp":1723556149000},"page":"2687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Vigeo Promotes Myotube Differentiation and Protects Dexamethasone-Induced Skeletal Muscle Atrophy via Regulating the Protein Degradation, AKT\/mTOR, and AMPK\/Sirt-1\/PGC1\u03b1 Signaling Pathway In Vitro and In Vivo"],"prefix":"10.3390","volume":"16","author":[{"given":"Yoon-Hee","family":"Cheon","sequence":"first","affiliation":[{"name":"Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 54538, Republic of Korea"},{"name":"Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, 460 Iksandae-ro, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-0733","authenticated-orcid":false,"given":"Chong-Hyuk","family":"Chung","sequence":"additional","affiliation":[{"name":"Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 54538, Republic of Korea"},{"name":"Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, 460 Iksandae-ro, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-0264","authenticated-orcid":false,"given":"Ju-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeung-Su","family":"Lee","sequence":"additional","affiliation":[{"name":"Musculoskeletal and Immune Disease Research Institute, School of Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 54538, Republic of Korea"},{"name":"Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, 460 Iksandae-ro, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1002\/cphy.c120033","article-title":"Muscle as a secretory organ","volume":"3","author":"Pedersen","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S0140-6736(12)61897-2","article-title":"Muscular dystrophies","volume":"381","author":"Mercuri","year":"2013","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1152\/physrev.00061.2017","article-title":"Sarcopenia: Aging-related loss of muscle mass and function","volume":"99","author":"Larsson","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1123S","DOI":"10.3945\/ajcn.2010.28608A","article-title":"Skeletal muscle loss: Cachexia, sarcopenia, and inactivity","volume":"91","author":"Evans","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/BOR.0b013e328358d59b","article-title":"Sarcopenia in older adults","volume":"24","author":"Walston","year":"2012","journal-title":"Curr. Opin. Rhematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.devcel.2013.12.020","article-title":"Gene regulatory networks and transcriptional mechanisms that control myogenesis","volume":"28","author":"Buckingham","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/0092-8674(78)90211-8","article-title":"Coordinate regulation of contractile protein synthesis during myoblast differentiation","volume":"13","author":"Devlin","year":"1978","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1126\/science.1065874","article-title":"Identification of ubiquitin ligases required for skeletal muscle atrophy","volume":"294","author":"Bodine","year":"2001","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jot.2022.11.005","article-title":"Is dexamethasone-induced muscle atrophy an alternative model for naturally aged sarcopenia model?","volume":"39","author":"Wang","year":"2022","journal-title":"J. Orthop. Translat."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yun, C.E., So, H.K., Vuong, T.A., Na, M.W., Anh, S., Lee, H.K., Kim, K.H., Kang, J.S., Bae, G.U., and Lee, S.J. (2021). Aronia upregulates myogenic differentiation and augments muscle mass and function through muscle metabolism. Front. Nutr., 23.","DOI":"10.3389\/fnut.2021.753643"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1055\/a-1891-3366","article-title":"A lignan from alnus japonica activates myogenesis and alleviates dexamethasone-induced myotube atrophy","volume":"89","author":"Lee","year":"2023","journal-title":"Planta Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Eun, S.Y., Cheon, Y.H., Park, G.D., Chung, C.H., Lee, C.H., Kim, J.Y., and Lee, M.S. (2021). Anti-osteoporosis effects of the Eleutherococcus senticosus, Achyranthes japonica, and Atractylodes japonica mixed extract fermented with nuruk. Nutrients, 13.","DOI":"10.3390\/nu13113904"},{"key":"ref_13","first-page":"106315","article-title":"Remedial effects of tilapia skin peptides against dexamethasone-induced muscle atrophy in mice by modulation of AKT\/FOXO3a and Sirt1\/PGC-1 signaling pathways","volume":"119","author":"Lin","year":"2024","journal-title":"J. Funct. Foods"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1097\/00075197-199905000-00002","article-title":"Glucocorticoids and muscle catabolism","volume":"2","author":"Hasselgren","year":"1999","journal-title":"Curr. Opin. Clin. Nutr Metab. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1159\/000057451","article-title":"The balance between glucocorticoids and insulin regulates muscle proteolysis via the ubiquitin-proteasome pathway","volume":"25","author":"Bailey","year":"1999","journal-title":"Miner. Electrolyte. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"810619","DOI":"10.4061\/2011\/810619","article-title":"Mitochondria and PGC-1\u03b1 in aging and age-associated diseases","volume":"2011","author":"Wenz","year":"2011","journal-title":"J. Aging Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12017","DOI":"10.1073\/pnas.0705070104","article-title":"AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha","volume":"104","author":"Handschin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21872","DOI":"10.1074\/jbc.M109.022749","article-title":"SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-gamma Co-activator-1alpha (PGC-1alpha) gene in skeletal muscle through the PGC-1alpha autoregulatory loop and interaction with MyoD","volume":"284","author":"Amat","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yochida, T., and Delafontaine, P. (2020). Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy. Cells, 9.","DOI":"10.3390\/cells9091970"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/ncb1101-1014","article-title":"Akt\/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo","volume":"3","author":"Bodine","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1471-4914(03)00138-2","article-title":"Molecular mechanisms modulating muscle mass","volume":"9","author":"Glass","year":"2003","journal-title":"Trends Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.celrep.2016.09.020","article-title":"S6K1 is required for increasing skeletal muscle force during hypertrophy","volume":"17","author":"Marabita","year":"2016","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.metabol.2013.05.018","article-title":"Suppression of atrogin-1 and MuRF1 prevents dexamethasone-induced atrophy of cultured myotubes","volume":"62","author":"Castillero","year":"2013","journal-title":"Metabolism"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1002\/jcsm.13057","article-title":"The beneficial therapeutic effects of plant-derived natural products for the treatment of sarcopenia","volume":"13","author":"Bagherniya","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Qu, Z., Zhou, S., Li, P., Liu, C., Yuan, B., Zhang, S., and Liu, A. (2021). Natural products and skeletal muscle health. J. Nutr. Biochem., 93.","DOI":"10.1016\/j.jnutbio.2021.108619"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1248\/yakushi.130.1471","article-title":"Drug development from natural fermentation products: Establishing a manufacturing process which maximizes the potential of microorganisms","volume":"130","author":"Nagao","year":"2010","journal-title":"Yakugaku Zasshi"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00253-009-1916-9","article-title":"Mixed fermentation for natural product drug discovery","volume":"83","author":"Pettit","year":"2009","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jep.2012.05.020","article-title":"Anti-inflammatory and anti-osteoarthritis effects of fermented Achyranthes japonica Nakai","volume":"142","author":"Lee","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s00774-009-0093-3","article-title":"The effects of Acanthopanax senticosus extract on bone turnover and bone mineral density in Korean postmenopausal women","volume":"27","author":"Hwang","year":"2009","journal-title":"J. Bone Miner. Metab."},{"key":"ref_31","first-page":"4514","article-title":"Eleutherococcus senticosus inhibits RANKL-induced osteoclast formation by attenuating the NF-\u03baB and MAPKs signaling pathway","volume":"10","author":"Yang","year":"2017","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.jep.2010.11.007","article-title":"Cornus kousa F. Buerger ex Miquel increases glucose uptake through activation of peroxisome proliferator-activated receptor \u03b3 and insulin sensitization","volume":"133","author":"Kim","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104088","DOI":"10.1016\/j.dib.2019.104088","article-title":"Anti-inflammatory effects of the combined extracts of Achyranthes japonica nakai and Aralia continentalis kitagawa in vitro and in vivo","volume":"25","author":"Woo","year":"2019","journal-title":"Data Brief"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhao, X., Kim, D., Suminda, G.G.D., Min, Y., Yang, J., Kim, M., Zhao, Y., Chosh, M., and Son, Y.O. (2021). Inhibitory effects of IL-6-mediated matrix metalloproteinase-3 and -13 by Achyranthes japonica Nakai root in osteoarthritis and rheumatoid arthritis mice models. Pharmaceutical, 14.","DOI":"10.3390\/ph14080776"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.5713\/ajas.2012.12438","article-title":"Antioxidant activities of Achyranthes japonica Nakai extract and its application to the pork sausages","volume":"26","author":"Park","year":"2013","journal-title":"Asian-Australas. J. Anim. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s12272-010-0606-6","article-title":"Atractylodes japonica koidzumi inhibits the production of proinflammatory cytokines through inhibition of the NF-kappaB\/IkappaB signal pathway in HMC-1 human mast cells","volume":"33","author":"Hong","year":"2010","journal-title":"Arch. Pharm. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"204892","DOI":"10.1093\/ecam\/neq006","article-title":"Anti-oxidative abilities of essential oils from Atractylodes ovate rhizome","volume":"2011","author":"Wang","year":"2011","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Han, Y., Jung, H.W., and Park, Y.K. (2012). The roots of Atractylodes japonica Koidzumi promote adipogenic differentiation via activation of the insulin signaling pathway in 3T3-L1 cells. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-154"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3892\/etm.2024.12496","article-title":"Vigeo attenuates cartilage and bone destruction in a collagen-induced arthritis mouse model by reducing production of pro-inflammatory cytokines","volume":"27","author":"Cheon","year":"2024","journal-title":"Exp. Ther. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hu, J., Wu, D., Sun, Y., Zhao, H., Wang, Y., Zhang, W., Su, F., Yang, B., Wang, Q., and Kuang, H. (2022). Comprehensive analysis of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves based on UPLC-MS\/MS: Separation and rapid qualitative and quantitative analysis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.865586"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ghimire, B.K., Seo, J.W., Kim, S.H., Chimire, B., Lee, J.G., Yu, C.Y., and Chung, I.M. (2021). Influence of harvesting time on phenolic and mineral profiles and their association with the antioxidant and cytotoxic effects of Atractylodes japonica Koidz. Agronomy, 11.","DOI":"10.3390\/agronomy11071327"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/1535370217749494","article-title":"Myogenic regulatory factors: The orchestrators of myogenesis after 30 years of discovery","volume":"243","author":"Asfour","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S1097-2765(02)00481-1","article-title":"Promoter-specific regulation of MyoD binding and signal transduction cooperate to pattern gene expression","volume":"9","author":"Bergstrom","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/0092-8674(93)90621-V","article-title":"MyoD or Myf-5 is required for the formation of skeletal muscle","volume":"75","author":"Rudnicki","year":"1993","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/364501a0","article-title":"Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene","volume":"364","author":"Hasty","year":"1993","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.semcdb.2017.11.010","article-title":"The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration","volume":"72","author":"Brun","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12020-012-9751-7","article-title":"Atrogin-1, MuRF-1, and sarcopenia","volume":"43","author":"Gumucio","year":"2013","journal-title":"Endocrine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1152\/physiolgenomics.00022.2013","article-title":"Altered gene expression patterns in muscle ring finger 1 null mice during denervation- and dexamethasone-induced muscle atrophy","volume":"45","author":"Furlow","year":"2023","journal-title":"Physiol. Genomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1186\/s12967-023-04369-z","article-title":"Mitochondrial dysfunction: Roles in skeletal muscle atrophy","volume":"21","author":"Chen","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jphs.2019.02.008","article-title":"Pretreatment with Tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia\/reperfusion injury via AMPK\/SIRT1\/PGC-1 alpha signaling pathway","volume":"139","author":"Tian","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/nature07813","article-title":"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity","volume":"458","author":"Feige","year":"2009","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"re11","DOI":"10.1126\/stke.2442004re11","article-title":"Molecular and cellular determinants of skeletal muscle atrophy and hypertrophy","volume":"2004","author":"Sartorelli","year":"2004","journal-title":"Sci. STKE"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/mus.20442","article-title":"Intracellular signaling during skeletal muscle atrophy","volume":"33","author":"Kandarian","year":"2006","journal-title":"Muscle Nerve"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/16\/2687\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:36:07Z","timestamp":1760110567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/16\/2687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,13]]},"references-count":53,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["nu16162687"],"URL":"https:\/\/doi.org\/10.3390\/nu16162687","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,13]]}}}