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This study examined how cancerous ascites from RCN9 rat colon carcinoma cells affected H9c2 cardiomyoblasts. Ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential, triggering apoptosis and autophagy. Neutralizing HMGB1 reduced myocardial damage. HMGB1 activated NF-κB and PI3K-AKT signaling via RAGE and TLR4, while berberine suppressed HMGB1, increased miR-181c-5p and miR-340-5p, and improved protection in a cachectic rat model.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/berberine-improves-cancer-derived-myocardial-impairment-in-experimental-cachexia-models-by-targeting-high-mobility-group-box-1/330598/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/berberine-improves-cancer-derived-myocardial-impairment-in-experimental-cachexia-models-by-targeting-high-mobility-group-box-1/330598.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What effects did cancer-derived ascites have on H9c2 cardiomyoblast cells?","Question",{"text":112,"@type":113},"Ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential, leading to apoptosis and autophagy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was HMGB1 implicated in the myocardial damage mechanism?",{"text":117,"@type":113},"HMGB1 was present in the ascites and, when neutralized by a specific antibody, mitigated the damage to myocardial cells; HMGB1 also activated NF-κB and PI3K-AKT via RAGE and TLR4.",{"name":119,"@type":110,"acceptedAnswer":120},"What did berberine do to reduce HMGB1-related cardiomyocyte injury?",{"text":121,"@type":113},"Berberine increased miR-181c-5p and miR-340-5p expression while suppressing HMGB1 in RCN9 cells, reduced HMGB1 receptor expression in cardiomyocytes, and protected the myocardium in a cachectic rat model.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330598,1790800682,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","Article  \nBerberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1  \nKei Goto 1, Rina Fujiwara-Tani 1,*, Shota Nukaga 1, Yoshihiro Miyagawa 1, Isao Kawahara 1, Ryoichi Nishida 1, Ayaka Ikemoto 1, Rika Sasaki 1, Ruiko Ogata 1, Shingo Kishi 2, Yi Luo 1, Kiyomu Fujii 1, Hitoshi Ohmori 1 and Hiroki Kuniyasu 1, *  \nCitation: Goto, K.; Fujiwara-Tani, R.; Nukaga, S.; Miyagawa, Y.; Kawahara, I.; Nishida, R.; Ikemoto, A.; Sasaki, R.; Ogata, R.; Kishi, S.; et al. Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1 . Int. J. Mol. Sci. 2024, 25, 4735. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25094735  \nAcademic Editor: Paola Sena  \nReceived: 2 April 2024  \nRevised: 23 April 2024  \nAccepted: 24 April 2024  \nPublished: 26 April 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan; [ilgfgtk@gmail.com](ilgfgtk@gmail.com) (K.G.); [shota.nukaga@gmail.com](shota.nukaga@gmail.com) (S.N.); [y.miya1103@gmail.com](y.miya1103@gmail.com) (Y.M.); [isao_kawahara@a011.broada.jp](isao_kawahara@a011.broada.jp) (I.K.); [g.m__r1@outlook.jp](g.m__r1@outlook.jp) (R.N.); [a.ikemoto.0916@gmail.com](a.ikemoto.0916@gmail.com) (A.I.); [rika0st1113v726296v@icloud.com](rika0st1113v726296v@icloud.com) (R.S.); [pkuma.og824@gmail.com](pkuma.og824@gmail.com) (R.O.); [lynantong@hotmail.com](lynantong@hotmail.com) (Y.L.); [toto1999-dreamtheater2006-sms@nifty.com](toto1999-dreamtheater2006-sms@nifty.com) (K.F.); [brahmus73@hotmail.com](brahmus73@hotmail.com) (H.O.)  \n2 Pathology Laboratory, Research Institute, Tokushukai Nozaki Hospital, 2-10-50 Tanigawa, Daito 574-0074, Osaka, Japan; [nmu6429@yahoo.co.jp](nmu6429@yahoo.co.jp)  \n* Correspondence: [rina_fuji@naramed-u.ac.jp](rina_fuji@naramed-u.ac.jp) (R.F.-T.); [cooninh@zb4.so-net.ne.jp](cooninh@zb4.so-net.ne.jp) (H.K.); Tel.: +81-744-22-3051 (R.F.-T. & H.K.); Fax: +81-744-25-7308 (R.F.-T. & H.K.)  \nAbstract: Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in acachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppr","cbCaiq12UbXzqFD0","https://ap.wps.com/l/cbCaiq12UbXzqFD0","pdf",3313754,15,"English","# Introduction\n## Cancer cachexia and cardiac disorder background\n## Connection to HMGB1 and signaling pathways\n## Experimental approach and outcomes","[{\"question\":\"What effects did cancer-derived ascites have on H9c2 cardiomyoblast cells?\",\"answer\":\"Ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential, leading to apoptosis and autophagy.\"},{\"question\":\"How was HMGB1 implicated in the myocardial damage mechanism?\",\"answer\":\"HMGB1 was present in the ascites and, when neutralized by a specific antibody, mitigated the damage to myocardial cells; HMGB1 also activated NF-κB and PI3K-AKT via RAGE and TLR4.\"},{\"question\":\"What did berberine do to reduce HMGB1-related cardiomyocyte injury?\",\"answer\":\"Berberine increased miR-181c-5p and miR-340-5p expression while suppressing HMGB1 in RCN9 cells, reduced HMGB1 receptor expression in cardiomyocytes, and protected the myocardium in a cachectic rat model.\"}]","Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1 | PDF",1789989500,38]