{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:58:21Z","timestamp":1790513901669,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T00:00:00Z","timestamp":1479340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5RO1\u2010AR063686"],"award-info":[{"award-number":["5RO1\u2010AR063686"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC81470970"],"award-info":[{"award-number":["NSFC81470970"]}],"id":[{"id":"10.13039\/501100001809","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":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Muscle wasting in chronic kidney disease (CKD) and other catabolic disorders contributes to morbidity and mortality, and there are no therapeutic interventions that regularly and safely block losses of muscle mass. We have obtained evidence that impaired IGF\u20101\/insulin signalling and increases in glucocorticoids, myostatin and\/or inflammatory cytokines that contribute to the development of muscle wasting in catabolic disorders by activating protein degradation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models of muscle wasting associated with CKD or dexamethasone administration, we measured protein synthesis and degradation and examined mechanisms by which ursolic acid, derived from plants, could block the loss of muscle mass stimulated by CKD or excessive levels of dexamethasone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using cultured C2C12 myotubes to study muscle wasting, we found that exposure to glucocorticoids cause loss of cell proteins plus an increase in myostatin; both responses are significantly suppressed by ursolic acid. Results from promoter and ChIP assays demonstrated a mechanism involving ursolic acid blockade of myostatin promoter activity that is related to CEBP\/\u03b4 expression. In mouse models of CKD\u2010induced or dexamethasone\u2010induced muscle wasting, we found that ursolic acid blocked the loss of muscle mass by stimulating protein synthesis and decreasing protein degradation. These beneficial responses included decreased expression of myostatin and inflammatory cytokines (e.g. TGF\u2010\u03b2, IL\u20106 and TNF\u03b1), which are initiators of muscle\u2010specific ubiquitin\u2010E3 ligases (e.g. Atrogin\u20101, MuRF\u20101 and MUSA1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ursolic acid improves CKD\u2010induced muscle mass by suppressing the expression of myostatin and inflammatory cytokines via increasing protein synthesis and reducing proteolysis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12162","type":"journal-article","created":{"date-parts":[[2016,11,18]],"date-time":"2016-11-18T01:56:56Z","timestamp":1479434216000},"page":"327-341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Suppression of muscle wasting by the plant\u2010derived compound ursolic acid in a model of chronic kidney disease"],"prefix":"10.1002","volume":"8","author":[{"given":"Rizhen","family":"Yu","sequence":"first","affiliation":[{"name":"Nephrology Division Changhai Hospital  Shanghai China"},{"name":"Nephrology Division Zhejiang Provincial People's Hospital  Hongzhou China"},{"name":"Nephrology Division Department of Medicine, Baylor College of Medicine  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010an","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Health Education, College of Preventive Medicine Third Military Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Nephrology Division Changhai Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Cao","sequence":"additional","affiliation":[{"name":"Nephrology Division Department of Medicine, Baylor College of Medicine  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Nephrology Division Department of Medicine, Baylor College of Medicine  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhya S.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Michael E. Debakey VA Medical Center  Houston TX USA"},{"name":"Nephrology Division Department of Medicine, Baylor College of Medicine  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyong","family":"Hu","sequence":"additional","affiliation":[{"name":"Nephrology Division Department of Medicine, Baylor College of Medicine  Houston TX 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