{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:58Z","timestamp":1760060758202,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea","award":["NRF-2020R1A6A1A03042854","RS-2023-00245441"],"award-info":[{"award-number":["NRF-2020R1A6A1A03042854","RS-2023-00245441"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Muscle atrophy is defined as reductions in muscle size and function and represents a critical concern affecting elderly populations, immobilized patients, and individuals following specific dietary regimens, such as fasting and low-protein diets. This study investigated the protective effects of Stellaria dichotoma root extract and its isolated bioactive compounds during muscle atrophy using both in vitro and in vivo experimental models. First, S. dichotoma root extract prevented dexamethasone (DEX)-induced atrophy in C2C12 myotubes. Through systematic solvent partitioning and resin chromatography, five compounds (1\u20135) were successfully isolated from the n-butanol fraction. Dichotomine B (2) was identified as the most abundant and bioactive constituent. Treatment with dichotomine B significantly preserved the myotube diameter, enhanced the fusion index, and maintained the myosin heavy chain protein level while suppressing key atrophic biomarkers, including FoxO3a, MuRF-1, and Atrogin-1, in DEX-treated myotubes. Furthermore, dichotomine B (2) reduced proteolysis in serum-free cultured C2C12 myotubes and in mice subjected to 48 h of fasting, preserving muscle mass and strength. These findings suggest that S. dichotoma root extract and its principal compound, dichotomine B (2), have promising therapeutic potential and provide an opportunity to develop novel pharmacological interventions against muscle wasting through suppression of proteolysis pathways.<\/jats:p>","DOI":"10.3390\/molecules30183839","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T17:08:17Z","timestamp":1758560897000},"page":"3839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Atrophic Effects of Dichotomine B from Stellaria dichotoma During Starvation-Induced Skeletal Muscle Atrophy"],"prefix":"10.3390","volume":"30","author":[{"given":"Jae-Yong","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan 15588, Gyeonggi-do, Republic of Korea"},{"name":"Lifecare Center, Huons N Co., Ltd., Gwacheon-si 13840, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6139-3773","authenticated-orcid":false,"given":"Uttapol","family":"Permpoon","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-hee","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-7502","authenticated-orcid":false,"given":"Ji Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Je-Seung","family":"Jeon","sequence":"additional","affiliation":[{"name":"Rural Development Administration (RDA), Eumseong-gun 27709, Chungcheongbuk-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-gyu","family":"Nam","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6988-1059","authenticated-orcid":false,"given":"Chul Young","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s12272-024-01493-2","article-title":"Advances in sarcopenia: Mechanisms, therapeutic targets, and intervention strategies","volume":"47","author":"Zheng","year":"2024","journal-title":"Arch. Pharm. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sergeeva, X.V., Lvova, I.D., and Sharlo, K.A. (2024). Disuse-induced muscle fatigue: Facts and assumptions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094984"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101270","DOI":"10.1016\/j.mam.2024.101270","article-title":"Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies","volume":"97","author":"Liu","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101319","DOI":"10.1016\/j.mam.2024.101319","article-title":"Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets","volume":"100","author":"Campanario","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1002\/jcsm.13243","article-title":"Sarcopenia and health-related quality of life: A systematic review and meta-analysis","volume":"14","author":"Beaudart","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1161\/CIRCULATIONAHA.123.064071","article-title":"Sarcopenia and cardiovascular diseases","volume":"147","author":"Damluji","year":"2023","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.2337\/dc09-S302","article-title":"Skeletal muscle insulin resistance is the primary defect in type 2 diabetes","volume":"32","author":"DeFronzo","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pradhan, R., Dieterich, W., Natarajan, A., Schwappacher, R., Reljic, D., Herrmann, H.J., Neurath, M.F., and Zopf, Y. (2024). Influence of amino acids and exercise on muscle protein turnover, particularly in cancer cachexia. Cancers, 16.","DOI":"10.3390\/cancers16101921"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2300347","DOI":"10.1002\/mnfr.202300347","article-title":"Nutritional strategies for muscle atrophy: Current evidence and underlying mechanisms","volume":"68","author":"Shen","year":"2024","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e659","DOI":"10.1002\/mco2.649","article-title":"Skeletal muscle: Molecular structure, myogenesis, biological functions, and diseases","volume":"5","author":"Feng","year":"2024","journal-title":"MedComm"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yoshida, 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_12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5187\/jast.2022.e114","article-title":"The roles of growth factors and hormones in the regulation of muscle satellite cells for cultured meat production","volume":"65","author":"Ahmad","year":"2023","journal-title":"J. Anim. Sci. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, S., Zeng, X., Ren, M., Mao, X., and Qiao, S. (2017). Novel metabolic and physiological functions of branched chain amino acids: A review. J. Anim. Sci. Biotechnol., 8.","DOI":"10.1186\/s40104-016-0139-z"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nakao, R., Abe, T., Yamamoto, S., and Oishi, K. (2019). Ketogenic diet induces skeletal muscle atrophy via reducing muscle protein synthesis and possibly activating proteolysis in mice. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-56166-8"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Permpoon, U., Moon, J., Kim, C.Y., and Nam, T.-g. (2025). Glucocorticoid-mediated skeletal muscle atrophy: Molecular mechanisms and potential therapeutic targets. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157616"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"42","DOI":"10.15252\/emmm.201404601","article-title":"REDD 1 functions at the crossroads between the therapeutic and adverse effects of topical glucocorticoids","volume":"7","author":"Baida","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pang, X.S., Zhang, P., Chen, X.P., and Liu, W.M. (2023). Ubiquitin-proteasome pathway in skeletal muscle atrophy. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1289537"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00424-010-0919-9","article-title":"The role and regulation of MAFbx\/atrogin-1 and MuRF1 in skeletal muscle atrophy","volume":"461","author":"Foletta","year":"2011","journal-title":"Pflug. Arch."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"38456","DOI":"10.1074\/jbc.M111.271270","article-title":"Translational suppression of atrophic regulators by microRNA-23a integrates resistance to skeletal muscle atrophy","volume":"286","author":"Wada","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"A92","DOI":"10.1016\/j.krcp.2012.04.625","article-title":"Calcineurin-NFAT signaling regulates atrogin-1 and MuRF1 via microRNA-23a (miR-23a) during muscle atrophy","volume":"31","author":"Hudson","year":"2012","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1096\/fj.09-151480","article-title":"FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1\/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy","volume":"24","author":"Zheng","year":"2010","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e785-97","DOI":"10.1152\/ajpendo.00646.2007","article-title":"The glucocorticoid receptor and FOXO1 synergistically activate the skeletal muscle atrophy-associated MuRF1 gene","volume":"295","author":"Waddell","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e10510","DOI":"10.7554\/eLife.10510","article-title":"Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system","volume":"4","author":"Xu","year":"2015","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gellhaus, B., B\u00f6ker, K.O., Schilling, A.F., and Saul, D. (2023). Therapeutic consequences of targeting the IGF-1\/PI3K\/AKT\/FOXO3 axis in sarcopenia: A narrative review. Cells, 12.","DOI":"10.3390\/cells12242787"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1021\/acs.jnatprod.4c00581","article-title":"Natural Products Have Increased Rates of Clinical Trial Success throughout the Drug Development Process","volume":"87","author":"Gadiya","year":"2024","journal-title":"J. Nat. Prod."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bae, S.-J., Choi, J.-W., Park, B.-J., Lee, J., Jo, E.-K., Lee, Y.-H., Kim, S.-B., and Yuk, J.-M. (2018). Protective effects of a traditional herbal extract from Stellaria dichotoma var. lanceolata against Mycobacterium abscessus infections. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207696"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s10600-021-03306-0","article-title":"Chemical constituents of Stellaria dichotoma var. lanceolata and their anti-inflammatory effect on lipopolysaccharide-stimulated RAW 264.7 cells","volume":"57","author":"Dong","year":"2021","journal-title":"Chem. Nat. Compd."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e3305","DOI":"10.7717\/peerj.3305","article-title":"Radix Stellariae extract prevents high-fat-diet-induced obesity in C57BL\/6 mice by accelerating energy metabolism","volume":"5","author":"Li","year":"2017","journal-title":"Peer J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1021\/np1003627","article-title":"\u03b2-Carboline alkaloids from Stellaria dichotoma var lanceolata and their anti-inflammatory activity","volume":"73","author":"Chen","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yu, F., Li, S., Li, B., Zhan, P., Wang, X., and Yang, J. (2025). Recent research progress of \u03b2-carbolines as privileged scaffold in the discovery of anticancer agent (2019\u20132024). Bioorg. Med. Chem., 129.","DOI":"10.1016\/j.bmc.2025.118325"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Du, H., Ma, F., Cao, Y., Bai, M., Gao, X., Yang, Z., Xu, Y., and Yan, Y. (2025). Bis(7)-harmine derivatives as potential multi-target anti-Alzheimer agents. Front. Chem., 13.","DOI":"10.3389\/fchem.2025.1545908"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1007\/s11064-023-03920-0","article-title":"Dichotomine B attenuates neuroinflammatory responses by regulating TLR4\/MyD88-mTOR signaling pathway in BV2 cells","volume":"48","author":"Zhou","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115261","DOI":"10.1016\/j.biopha.2023.115261","article-title":"Protective effects of Radix Stellariae extract against Alzheimer\u2019s disease via autophagy activation in Caenorhabditis elegans and cellular models","volume":"165","author":"Long","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cho, C.H., Chae, S.H., Thi, N.H.L., Um, S.H., Lee, S., Yu, J.S., Kang, K.S., and Kim, K.H. (2025). Lambertianic Acid from Platycladus orientalis inhibits muscle atrophy in dexamethasone-induced C2C12 muscle atrophy cells. Plants, 14.","DOI":"10.3390\/plants14091357"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100871","DOI":"10.1016\/j.diff.2025.100871","article-title":"Myogenic and adipogenic potential of porcine muscle satellite cells isolated by flow cytometry","volume":"144","author":"Vincent","year":"2025","journal-title":"Differentiation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1152\/ajpcell.00851.2024","article-title":"Multi-therapeutic strategy targeting Akt-mTOR and FoxO1 pathway to counteract skeletal muscle atrophy consecutive to hypoxia","volume":"328","author":"Bensaid","year":"2025","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Paolini, A., Omairi, S., Mitchell, R., Vaughan, D., Matsakas, A., Vaiyapuri, S., Ricketts, T., Rubinsztein, D.C., and Patel, K. (2021). Attenuation of autophagy impacts on muscle fibre development, starvation induced stress and fibre regeneration following acute injury. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-04140-8"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vendelbo, M.H., M\u00f8ller, A.B., Christensen, B., Nellemann, B., Clasen, B.F.F., Nair, K.S., J\u00f8rgensen, J.O.L., Jessen, N., and M\u00f8ller, N. (2014). Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102031"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Layman, D.K. (2024). Impacts of protein quantity and distribution on body composition. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1388986"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1113\/EP091937","article-title":"Mitigating disuse-induced skeletal muscle atrophy in ageing: Resistance exercise as a critical countermeasure","volume":"109","author":"McKendry","year":"2024","journal-title":"Exp. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ren, Y., Gao, Y.B., Yu, D.X., and Huang, H.B. (2025). Beta-hydroxy-beta-methyl butyrate supplementation in critically ill patients: A systematic review and meta-analysis of randomized controlled trials. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1505797"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ebert, S.M., Nicolas, C.S., Schreiber, P., Lopez, J.G., Taylor, A.T., Judge, A.R., Judge, S.M., Rasmussen, B.B., Talley, J.J., and R\u00e8me, C.A. (2024). Ursolic acid induces beneficial changes in skeletal muscle mRNA expression and increases exercise participation and performance in dogs with age-related muscle atrophy. Animals, 14.","DOI":"10.3390\/ani14020186"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1248\/cpb.52.1194","article-title":"Bioactive constituents from Chinese natural medicines. XIV. New glycosides of \u03b2-carboline-type alkaloid, neolignan, and phenylpropanoid from Stellaria dichotoma L. var. lanceolata and their antiallergic activities","volume":"52","author":"Morikawa","year":"2004","journal-title":"Chem. Pharm. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.3390\/molecules18021672","article-title":"The Passiflora tripartita (Banana Passion) fruit: A source of bioactive flavonoid C-glycosides isolated by HSCCC and characterized by HPLC\u2013DAD\u2013ESI\/MS\/MS","volume":"18","author":"Simirgiotis","year":"2013","journal-title":"Molecules"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/18\/3839\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:13Z","timestamp":1760035633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/18\/3839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":44,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["molecules30183839"],"URL":"https:\/\/doi.org\/10.3390\/molecules30183839","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2025,9,22]]}}}