{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:52:14Z","timestamp":1790812334257,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873814"],"award-info":[{"award-number":["81873814"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91649120"],"award-info":[{"award-number":["91649120"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009102","name":"Education Department of Jiangxi Province","doi-asserted-by":"publisher","award":["20181BCD40001"],"award-info":[{"award-number":["20181BCD40001"]}],"id":[{"id":"10.13039\/501100009102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009102","name":"Education Department of Jiangxi Province","doi-asserted-by":"publisher","award":["2018ACB21036"],"award-info":[{"award-number":["2018ACB21036"]}],"id":[{"id":"10.13039\/501100009102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009102","name":"Education Department of Jiangxi Province","doi-asserted-by":"publisher","award":["20192BCB23004"],"award-info":[{"award-number":["20192BCB23004"]}],"id":[{"id":"10.13039\/501100009102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009102","name":"Education Department of Jiangxi Province","doi-asserted-by":"publisher","award":["jxsq2018106036"],"award-info":[{"award-number":["jxsq2018106036"]}],"id":[{"id":"10.13039\/501100009102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Handelin is a bioactive compound from\n \n Chrysanthemum indicum<\/jats:styled-content>\n L\n <\/jats:italic>\n . that improves motor function and muscle integrity during aging in\n \n Caenorhabditis elegans<\/jats:styled-content>\n <\/jats:italic>\n . This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A tumour necrosis factor (TNF)\u2010\u03b1\u2010induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes\n in vitro<\/jats:italic>\n . Lipopolysaccharide (LPS)\u2010treated 8\u2010week\u2010old model mice and 23\u2010month\u2010old (aged) mice were used to examine the therapeutic effects of handelin on cachexia\u2010 and aging\u2010induced muscle atrophy, respectively,\n in vivo<\/jats:italic>\n . Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (\n P<\/jats:italic>\n \u00a0<\u00a00.05), and enhanced mitochondrial respiratory (\n P<\/jats:italic>\n \u00a0<\u00a00.05). In TNF\u2010\u03b1\u2010induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin\u2010like growth factor\n (Igf1<\/jats:italic>\n ) mRNA expression and phosphorylated protein kinase B protein levels (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Handelin also reduced atrogin\u20101 expression, inhibited nuclear factor\u2010\u03baB activation and reduced mRNA levels of interleukin (\n Il<\/jats:italic>\n )\n 6<\/jats:italic>\n ,\n Il1b<\/jats:italic>\n and chemokine ligand 1 (\n Cxcl1<\/jats:italic>\n ) (\n P<\/jats:italic>\n \u00a0<\u00a00.05). In LPS\u2010treated mice, handelin increased body weight (\n P<\/jats:italic>\n \u00a0<\u00a00.05), the weight (\n P<\/jats:italic>\n \u00a0<\u00a00.01) and cross\u2010sectional area (CSA) of the soleus muscle (\n P<\/jats:italic>\n \u00a0<\u00a00.0001) and improved motor function (\n P<\/jats:italic>\n \u00a0<\u00a00.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (\n P<\/jats:italic>\n \u00a0=\u00a00.06) and CSA of the tibialis anterior and gastrocnemius muscles (\n P<\/jats:italic>\n \u00a0<\u00a00.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of\n Igf1<\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0<\u00a00.01), anti\u2010inflammatory cytokine\n Il10<\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0<\u00a00.01), mitochondrial biogenesis genes (\n P<\/jats:italic>\n \u00a0<\u00a00.05) and antioxidant\u2010related enzymes (\n P<\/jats:italic>\n \u00a0<\u00a00.05) and strengthened Sod and Cat enzyme activity (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of\n Fbxo32<\/jats:italic>\n ,\n Mstn<\/jats:italic>\n ,\n Cxcl1<\/jats:italic>\n ,\n Il1b<\/jats:italic>\n and\n Tnf<\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0<\u00a00.05), and decreased IL\u20101\u03b2 levels in serum (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Handelin ameliorated cachexia\u2010 and aging\u2010induced skeletal muscle atrophy\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n , by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13381","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T19:11:42Z","timestamp":1701112302000},"page":"173-188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Handelin alleviates cachexia\u2010 and aging\u2010induced skeletal muscle atrophy by improving protein homeostasis and inhibiting inflammation"],"prefix":"10.1002","volume":"15","author":[{"given":"Hui\u2010Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Metabolic Control and Aging, Human Aging Research Institute and School of Life Science Nanchang University and Jiangxi Key Laboratory of Human Aging Nanchang 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