{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:55:00Z","timestamp":1781808900612,"version":"3.54.5"},"reference-count":80,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003693","name":"Korea Institute of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003693","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Sarcopenia, an age\u2010related decline in skeletal muscle mass and function, contributes to frailty and increased morbidity in the elderly. This necessitates the development of effective interventions to combat muscle atrophy. This study investigated the therapeutic potential of <jats:styled-content style=\"fixed-case\">\n<jats:italic>Poncirus trifoliata<\/jats:italic>\n<\/jats:styled-content> ethanol extract (PT) and its coumarin derivatives against dexamethasone (DEX)\u2010induced muscle atrophy. We employed in\u00a0vitro and in\u00a0vivo models of DEX\u2010induced muscle atrophy. C2C12 myotubes were used for mechanistic studies. C57BL\/6J mice received DEX injections and oral PT supplementation (50\u2009mg\/kg\/day) to evaluate effects on muscle mass, function, gene expression, and gut microbiota composition. In\u00a0vitro, PT enhanced protein synthesis, mitochondrial biogenesis, and myogenic differentiation in DEX\u2010exposed myotubes, with auraptene, ponciol, and triphasiol identified as key bioactive coumarins. In\u00a0vivo, PT significantly attenuated DEX\u2010induced muscle atrophy, increasing tibialis anterior muscle mass by 36% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), grip strength by 31% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and maximal running speed by 18% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Mechanistically, PT upregulated genes associated with muscle function and mitochondrial health. Furthermore, PT modulated gut microbiota composition, notably increasing <jats:italic>Phocaeicola vulgatus<\/jats:italic> abundance 2.2\u2010fold, which correlated with improved muscle performance (<jats:italic>R<\/jats:italic>\u2009=\u20090.58, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). These findings suggest that PT and its coumarin derivatives, particularly auraptene, ponciol, and triphasiol, hold promise as therapeutic agents for combating muscle atrophy. The observed benefits may be mediated through enhanced protein synthesis, improved mitochondrial function, and modulation of the gut\u2010muscle axis.<\/jats:p>","DOI":"10.1002\/ptr.8478","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T05:38:51Z","timestamp":1742017131000},"page":"2409-2427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp><i>Poncirus trifoliata<\/i><\/scp> Extract and Its Active Coumarins Alleviate Dexamethasone\u2010Induced Skeletal Muscle Atrophy by Regulating Protein Synthesis, Mitochondrial Biogenesis, and Gut Microbiota"],"prefix":"10.1002","volume":"39","author":[{"given":"Hyejin","family":"Ko","sequence":"first","affiliation":[{"name":"Natural Product Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam Thi","family":"Le","sequence":"additional","affiliation":[{"name":"Natural Product Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Bao","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Natural Product Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"},{"name":"College of Dentistry, Department of Biochemistry and Molecular Biology Gangneung Wonju National University  Gangneung Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Woo","family":"Kang","sequence":"additional","affiliation":[{"name":"Natural Product Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Hyun","family":"Cha","sequence":"additional","affiliation":[{"name":"Natural Product Informatics Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"},{"name":"Division of Bio\u2010Medical Science and Technology, KIST School University of Science and Technology (UST)  Daejeon Republic of Korea"},{"name":"Department of Convergence Medicine, Wonju College of Medicine Yonsei University  Wonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nain","family":"Yang","sequence":"additional","affiliation":[{"name":"Natural Product Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hoon","family":"Jung","sequence":"additional","affiliation":[{"name":"Natural Product Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"},{"name":"Division of Bio\u2010Medical Science and Technology, KIST School University of Science and Technology (UST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5618-3040","authenticated-orcid":false,"given":"Myungsuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Natural Product Research Center Korea Institute of Science and Technology (KIST)  Gangneung Republic of Korea"},{"name":"Division of Bio\u2010Medical Science and Technology, KIST School University of Science and Technology (UST)  Daejeon Republic of Korea"},{"name":"Department of Convergence Medicine, Wonju College of Medicine Yonsei University  Wonju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2063179"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-010-0011-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020497"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112199"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12518"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065874"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0209-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-198706000-00004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-016-9592-1"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3869"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27113641"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200048"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00032719.2013.871548"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afy169"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.064071"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2010.02.002"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12082"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12081624"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15112526"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2010.28608E"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2022.105387"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.11.010"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109971"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2018.11.005"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i29.8787"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2309683"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84031-0"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02114"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6223"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.22.422"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2024.106384"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0515-8"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00325"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28010255"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00061.2017"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42005-y"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12784"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1036196"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1757-4749-5-23"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.71.12.8228-8235.2005"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.10.003"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12102936"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25483"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1890\/0012-9658(2001)082[0290:FMMTCD]2.0.CO;2"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061217"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S186600"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.694217"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16081130"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46116-y"},{"key":"e_1_2_11_52_1","unstructured":"Oksanen J. F. G.Blanchet M.Friendly et\u00a0al.2018.\u201cvegan: Community Ecology Package. R Package Version 2.5\u20132.\u201dhttps:\/\/CRAN.R\u2010project.org\/package=vegan."},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/194821"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13132"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/PHM.0b013e31822dea3c"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-9574LSF"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-017-1934-z"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-020-00840-y"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607795103"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.4162\/nrp.2022.16.2.147"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0606"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg0088"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12393"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2318-13-104"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14194120"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2022.11.005"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.06.012"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00648-0"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14091859"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107210"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2263207"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.09.003"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1287271"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02517-22"},{"key":"e_1_2_11_75_1","article-title":"The Causal Effect Between Gut Microbiota and Sarcopenia Related Traits: A Large\u2010Scale Bidirectional Mendelian Randomization","volume":"1","author":"Xu T.","year":"2023","journal-title":"Research Square"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.01.027"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.09.040"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01041-8"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113876"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101739"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9932218"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.8478","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T12:37:45Z","timestamp":1754483865000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.8478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,15]]},"references-count":80,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/ptr.8478"],"URL":"https:\/\/doi.org\/10.1002\/ptr.8478","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,15]]},"assertion":[{"value":"2024-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}