{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:59:05Z","timestamp":1790935145683,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360829"],"award-info":[{"award-number":["82360829"]}],"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":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Around 80% of patients with advanced cancer have cancer cachexia (CC), a serious complication for which there are currently no FDA\u2010approved treatments. Nuciferine (NF) is the main active ingredient of lotus leaf, which has anti\u2010inflammatory, anti\u2010tumour and other effects. The purpose of this work was to explore the target and mechanism of NF in preventing cancer cachexia\u2010induced muscle atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The action of NF against CC\u2010induced muscle atrophy was determined by constructing an animal model with a series of behavioural tests, H&amp;E staining and related markers. Network pharmacology and molecular docking were used to preliminarily determine the mechanism and targets of NF against CC\u2010induced muscle atrophy. The mechanisms of NF in treating CC\u2010induced muscle atrophy were verified by western blotting. Molecular dynamics simulation (MD), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) were used to validate the key target of NF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After 13\u2009days of NF treatment, the reduction of limb grip strength and hanging time in LLC model mice increased by 29.7% and 192.2% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001). Gastrocnemius and quadriceps muscles weight\/initial body weight (0.98\u2009\u00b1\u20090.11 and 1.20\u2009\u00b1\u20090.17) and cross\u2010sectional area of muscle fibres (600\u20131600\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      ) of NF\u2010treated mice were significantly higher than those of the model group (0.84\u2009\u00b1\u20090.10, 0.94\u2009\u00b1\u20090.09, 400\u2013800\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      , respectively) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001). NF treatment also decreased the MyHC (myosin heavy chain) degradation and the protein levels of muscle\u2010specific E3 ubiquitin ligases Atrogin1 and MuRF1 in the model group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05). Network pharmacology revealed that NF majorly targeted AKT1, TNF and HSP90AA1 to regulate PI3K\u2010Akt and inflammatory pathways. Molecular docking predicted that NF bound best to HSP90AA1. Mechanism analysis demonstrated that NF regulated NF\u2010\u03baB and AKT\u2013mTOR pathways for alleviating muscle wasting in tumour bearing mice. The results of MD, DARTS and SPR further confirmed that HSP90AA1 was the direct target of NF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, we first discovered that NF retards CC\u2010induced muscle atrophy by regulating AKT\u2013mTOR and NF\u2010\u03baB signalling pathways through directly binding\u00a0HSP90AA1, suggesting that NF may be an effective treatment for cancer cachexia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13777","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T21:15:47Z","timestamp":1743714947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nuciferine Attenuates Cancer Cachexia\u2010Induced Muscle Wasting in Mice via HSP90AA1"],"prefix":"10.1002","volume":"16","author":[{"given":"Xueyan","family":"An","sequence":"first","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulan","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyue","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awaguli","family":"Dawuti","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoxue","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7880-7572","authenticated-orcid":false,"given":"Abudumijiti","family":"Abulizi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy Shihezi University  Shihezi China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs Peking 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