{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:55:11Z","timestamp":1767207311728,"version":"build-2238731810"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1C1C2006896"],"award-info":[{"award-number":["2021R1C1C2006896"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["121015033SB010"],"award-info":[{"award-number":["121015033SB010"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014189","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry","doi-asserted-by":"crossref","award":["2021R1C1C2006896"],"award-info":[{"award-number":["2021R1C1C2006896"]}],"id":[{"id":"10.13039\/501100014189","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014189","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry","doi-asserted-by":"crossref","award":["121015033SB010"],"award-info":[{"award-number":["121015033SB010"]}],"id":[{"id":"10.13039\/501100014189","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Nutrients"],"abstract":"<jats:p>Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the myogenic effect of RGX365 on mouse myoblast cells (C2C12) and dexamethasone (10 \u00b5M)-induced atrophy of differentiated C2C12. RGX365-treated myotube diameters and myosin heavy chain (MyHC) expression levels were analyzed using immunofluorescence. We evaluated the myogenic effects of RGX365 in aging sarcopenic mice. RGX365 increased myoblast differentiation and MyHC expression, and attenuated the muscle atrophy-inducing F-box (Atrogin-1) and muscle RING finger 1 (MuRF1) expression. Notably, one month of oral administration of RGX365 to 23-month-old sarcopenic mice improved muscle fiber size and the expression of skeletal muscle regeneration-associated molecules. In conclusion, rare ginsenosides, agonists of steroid receptors, can ameliorate skeletal muscle atrophy during long-term administration.<\/jats:p>","DOI":"10.3390\/nu15194307","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T10:48:33Z","timestamp":1696848513000},"page":"4307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RETRACTED: Myogenesis Effects of RGX365 to Improve Skeletal Muscle Atrophy"],"prefix":"10.3390","volume":"15","author":[{"given":"Hye-Jin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Ji","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Ah","family":"Lee","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 63243, Republic of Korea"},{"name":"Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, 66123 Saarbruecken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1933-8629","authenticated-orcid":false,"given":"Dong","family":"Baek","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-6960","authenticated-orcid":false,"given":"Jong","family":"Heo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyu","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"},{"name":"AREZ Co., Ltd., Daejeon 34036, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4336-5221","authenticated-orcid":false,"given":"Wonhwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.phrs.2015.05.010","article-title":"Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action","volume":"99","author":"Dutt","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"174995","DOI":"10.1016\/j.ejphar.2022.174995","article-title":"Natural products: Potential therapeutic agents to prevent skeletal muscle atrophy","volume":"925","author":"Yadav","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_3","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_4","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_5","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/scrt358","article-title":"MYOD mediates skeletal myogenic differentiation of human amniotic fluid stem cells and regeneration of muscle injury","volume":"4","author":"Kim","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.stemcr.2018.01.027","article-title":"Loss of MyoD and Myf5 in Skeletal Muscle Stem Cells Results in Altered Myogenic Programming and Failed Regeneration","volume":"10","author":"Yamamoto","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1073\/pnas.1401732111","article-title":"Requirement of MEF2A, C, and D for skeletal muscle regeneration","volume":"111","author":"Liu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fphys.2018.00215","article-title":"Mechanistic Role of Reactive Oxygen Species and Therapeutic Potential of Antioxidants in Denervation- or Fasting-Induced Skeletal Muscle Atrophy","volume":"9","author":"Qiu","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.bbrc.2015.02.144","article-title":"TLR2 deficiency attenuates skeletal muscle atrophy in mice","volume":"459","author":"Kim","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1378\/chest.06-1655","article-title":"Six-minute walking-induced systemic inflammation and oxidative stress in muscle-wasted COPD patients","volume":"131","author":"Heijdra","year":"2007","journal-title":"Chest"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1113\/jphysiol.2007.141119","article-title":"Antioxidant administration attenuates mechanical ventilation-induced rat diaphragm muscle atrophy independent of protein kinase B (PKB Akt) signalling","volume":"585","author":"McClung","year":"2007","journal-title":"J. Physiol."},{"key":"ref_12","first-page":"240","article-title":"Oxidative stress and disuse muscle atrophy: Cause or consequence?","volume":"15","author":"Powers","year":"2012","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_13","first-page":"45","article-title":"Pathological state or cause of sarcopenia","volume":"27","author":"Matsui","year":"2017","journal-title":"Clin. Calcium"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7070","DOI":"10.1021\/acsabm.1c00688","article-title":"Thermosensitive Hydrogel Harboring CD146\/IGF-1 Nanoparticles for Skeletal-Muscle Regeneration","volume":"4","author":"Lee","year":"2021","journal-title":"ACS Appl. Bio. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Peris-Moreno, D., Cussonneau, L., Combaret, L., Polge, C., and Taillandier, D. (2021). Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control. Molecules, 26.","DOI":"10.3390\/molecules26020407"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S2213-8587(14)70034-8","article-title":"Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases","volume":"2","author":"Kalyani","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.arr.2018.07.005","article-title":"The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans","volume":"47","author":"Wilkinson","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_18","first-page":"177","article-title":"Clinical definition of sarcopenia","volume":"11","author":"Santilli","year":"2014","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1164\/rccm.201710-2140CI","article-title":"Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease. What We Know and Can Do for Our Patients","volume":"198","author":"Jaitovich","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1152\/japplphysiol.00981.2012","article-title":"Pathophysiology of muscle dysfunction in COPD","volume":"114","author":"Gea","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1465-9921-9-12","article-title":"Diaphragm adaptations in patients with COPD","volume":"9","author":"Ottenheijm","year":"2008","journal-title":"Respir. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/jcsm.12587","article-title":"Sarcopenia and peripheral arterial disease: A systematic review","volume":"11","author":"Pizzimenti","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"743710","DOI":"10.3389\/fcvm.2021.743710","article-title":"Relationship Between Sarcopenia and Cardiovascular Diseases in the Elderly: An Overview","volume":"8","author":"He","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yanagi, N., Koike, T., Kamiya, K., Hamazaki, N., Nozaki, K., Ichikawa, T., Matsunaga, A., Kuroiwa, M., and Arai, M. (2021). Assessment of Sarcopenia in the Intensive Care Unit and 1-Year Mortality in Survivors of Critical Illness. Nutrients, 13.","DOI":"10.3390\/nu13082726"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"G241","DOI":"10.1152\/ajpgi.00373.2020","article-title":"Sarcopenia in chronic liver disease: Mechanisms and countermeasures","volume":"320","author":"Allen","year":"2021","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1142\/S0192415X20500536","article-title":"Rgx365, a Rare Protopanaxatriol-Type Ginsenoside Fraction from Black Ginseng, Suppresses Inflammatory Gene iNOS via the Iinhibition of p-STAT-1 and NF-\u03baB","volume":"48","author":"Jeong","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Park, H.H., Kim, H., Lee, H.S., Seo, E.U., Kim, J.E., Lee, J.H., Mun, Y.H., Yoo, S.Y., An, J., and Yun, M.Y. (2021). PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses. Biomaterials, 273.","DOI":"10.1016\/j.biomaterials.2021.120827"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1080\/15287394.2019.1596183","article-title":"Inhibitory effects of protopanaxatriol type ginsenoside fraction (Rgx365) on particulate matter-induced pulmonary injury","volume":"82","author":"Lee","year":"2019","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, M., Wang, Y., Deng, S., Lian, Z., and Yu, K. (2022). Skeletal muscle oxidative stress and inflammation in aging: Focus on antioxidant and anti-inflammatory therapy. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.964130"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hyatt, H.W., and Powers, S.K. (2021). Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity. Antioxidants, 10.","DOI":"10.3390\/antiox10040588"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1749-6632.2012.06738.x","article-title":"Role of PGC-1alpha signaling in skeletal muscle health and disease","volume":"1271","author":"Kang","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1002\/jcp.25737","article-title":"The Role of Exercise and TFAM in Preventing Skeletal Muscle Atrophy","volume":"232","author":"Theilen","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cger.2016.08.002","article-title":"Pathogenesis and Management of Sarcopenia","volume":"33","author":"Dhillon","year":"2017","journal-title":"Clin. Geriatr. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/ggi.12723","article-title":"Sarcopenia: Prevalence and associated factors based on different suggested definitions in community-dwelling older adults","volume":"16","author":"Kim","year":"2016","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.afos.2022.12.002","article-title":"Nutrition in the prevention and management of sarcopenia\u2014A special focus on Asian Indians","volume":"8","author":"Bhattacharya","year":"2022","journal-title":"Osteoporos Sarcopenia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1017\/S002966511500422X","article-title":"Nutrition and physical activity for the prevention and treatment of age-related sarcopenia","volume":"75","author":"Bosaeus","year":"2016","journal-title":"Proc. Nutr. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jgr.2020.02.004","article-title":"Pharmacological potential of ginseng and its major component ginsenosides","volume":"45","author":"Ratan","year":"2021","journal-title":"J. Ginseng. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Han, M.J., Park, S.J., Lee, S.J., and Choung, S.Y. (2022). The Panax ginseng Berry Extract and Soluble Whey Protein Hydrolysate Mixture Ameliorates Sarcopenia-Related Muscular Deterioration in Aged Mice. Nutrients, 14.","DOI":"10.3390\/nu14040799"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.jgr.2020.12.004","article-title":"Review of ginsenosides targeting mitochondrial function to treat multiple disorders: Current status and perspectives","volume":"45","author":"Huang","year":"2021","journal-title":"J. Ginseng. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Metwaly, A.M., Lianlian, Z., Luqi, H., and Deqiang, D. (2019). Black Ginseng and Its Saponins: Preparation, Phytochemistry and Pharmacological Effects. Molecules, 24.","DOI":"10.3390\/molecules24101856"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jin, S., Jeon, J.H., Lee, S., Kang, W.Y., Seong, S.J., Yoon, Y.R., Choi, M.K., and Song, I.S. (2019). Detection of 13 Ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, Compound K, 20(S)-Protopanaxadiol, and 20(S)-Protopanaxatriol) in Human Plasma and Application of the Analytical Method to Human Pharmacokinetic Studies Following Two Week-Repeated Administration of Red Ginseng Extract. Molecules, 24.","DOI":"10.3390\/molecules24142618"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Valdes-Gonzalez, J.A., Sanchez, M., Moratilla-Rivera, I., Iglesias, I., and Gomez-Serranillos, M.P. (2023). Immunomodulatory, Anti-Inflammatory, and Anti-Cancer Properties of Ginseng: A Pharmacological Update. Molecules, 28.","DOI":"10.3390\/molecules28093863"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1142\/S0192415X19500630","article-title":"Inhibitory Effects of Black Ginseng on Particulate Matter-Induced Pulmonary Injury","volume":"47","author":"Lee","year":"2019","journal-title":"Am. J. Chin. Med."}],"updated-by":[{"DOI":"10.3390\/nu16193412","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"record-id":"57837"},{"DOI":"10.3390\/nu16193412","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000}}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/19\/4307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T14:25:01Z","timestamp":1754231101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/19\/4307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,9]]},"references-count":46,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["nu15194307"],"URL":"https:\/\/doi.org\/10.3390\/nu15194307","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,9]]}}}