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The molecular mechanism of cisplatin\u2010induced muscle atrophy is not clearly understood. However, recent significant advances indicate that it is related to an imbalance in both the protein status and apoptosis. Capsaicin (CAP) is one of the major ingredients in chilli peppers. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation with particular therapeutic potential in muscle atrophy. However, the mechanisms underlying its protective effects against cisplatin\u2010induced muscle loss and atrophy remain largely unknown. This study aims to investigate capsaicin's beneficial effects on cisplatin\u2010induced muscle loss and atrophy in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The anti\u2010muscle\u2010atrophic effect of capsaicin on cisplatin\u2010induced muscle loss was investigated using in vivo and in vitro studies. By using the pretreatment model, pretreated capsaicin for 24\u00a0h and treated with cisplatin for 48\u00a0h, we utilized a C\n                      <jats:sub>2<\/jats:sub>\n                      C\n                      <jats:sub>12<\/jats:sub>\n                      myotube formation model where cell viability analysis, immunofluorescence, and protein expression were measured to investigate the effect of capsaicin in hampering cisplatin\u2010induced muscle atrophy. C57BL\/6 mice were administered capsaicin (10, 40\u00a0mg\/kg BW) as a pretreatment for 5\u00a0weeks and cisplatin (3\u00a0mg\/kg BW) for seven consecutively days to assess muscle atrophy in an animal model for protein and oxidative stress examination, and the grip strength was tested to evaluate the muscle strength.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our study results indicated that cisplatin caused lower cell viability and showed a subset of hallmark signs typically recognized during atrophy, including severe reduction in the myotube diameter, repression of Akt, and mTOR protein expression. However, pretreatment with capsaicin could ameliorate cisplatin\u2010induced muscle atrophy by up\u2010regulating the protein synthesis in skeletal muscle as well as down\u2010regulating the markers of protein degradation. Additionally, capsaicin was able to downregulate the protein expression of apoptosis\u2010related markers, activated TRPV1 and autophagy progress modulation and the recovery of lysosome function. In vivo, capsaicin could relieve oxidative stress and cytokine secretion while modulating autophagy\u2010related lysosome fusion, improving\u00a0grip strength, and alleviating cisplatin\u2010induced body weight loss and gastrocnemius atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that capsaicin\u00a0can restore cisplatin\u2010induced imbalance between protein synthesis and protein degradation pathways and it may have protective effects against cisplatin\u2010induced muscle atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13120","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T23:36:30Z","timestamp":1668814590000},"page":"182-197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Capsaicin alleviates cisplatin\u2010induced muscle loss and atrophy in vitro and in vivo"],"prefix":"10.1002","volume":"14","author":[{"given":"Ko\u2010Chieh","family":"Huang","sequence":"first","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Fen","family":"Chiang","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsui\u2010Chin","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin\u2010Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Han","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition Taipei Medical University  Taipei Taiwan"},{"name":"Cancer Progression Research Center National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-2618","authenticated-orcid":false,"given":"Shih\u2010Min","family":"Hsia","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition Taipei Medical University  Taipei Taiwan"},{"name":"Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition Taipei Medical University  Taipei Taiwan"},{"name":"School of Food and Safety, College of Nutrition Taipei Medical University  Taipei Taiwan"},{"name":"Nutrition Research Center Taipei Medical University Hospital  Taipei Taiwan"},{"name":"TMU Research Center for Digestive Medicine Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4081\/ejtm.2018.7590"},{"key":"e_1_2_8_3_1","first-page":"1663","article-title":"Cisplatin and platinum drugs at the molecular level. 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