{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:03:36Z","timestamp":1771049016575,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011705","name":"Korea Institute of Marine Science & Technology Promotion","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011705","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003566","name":"Ministry of Oceans and Fisheries, Korea","doi-asserted-by":"publisher","award":["20210466"],"award-info":[{"award-number":["20210466"]}],"id":[{"id":"10.13039\/501100003566","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Cancer cachexia is a wasting syndrome with significant loss of body weight and muscle mass caused by inflammation and abnormal metabolism in advanced cancers. Despite its detrimental effects on patients, no standard treatment has been established for this syndrome. Thus, finding new treatments will broaden the remedy for cancer cachexia, resulting in increased survival in patients with terminal cancer. Methods: In this study, we assessed the therapeutic effects of the natural compound polydatin on cancer cachexia in vitro and in vivo using C2C12 myoblasts and CT26-bearing mice to elucidate the mechanisms of how it ameliorates muscle atrophy. At the same time, molecular docking analysis of polydatin with the IL6\/STAT3 signaling pathway was conducted to demonstrate their interaction. Results: Our data showed that polydatin treatment at 100 mg\/kg could attenuate symptoms of cancer cachexia including body weight loss, muscle strength and severe inflammation. Muscle mass reduction\u2014with the shrinking of muscle fibers, an increase in the expression levels of two E3 ubiquitin ligases (MuRF1 and Atrogin-1) and interleukin-6, and a downregulation of MyHC\u2014observed in CT26-bearing mice was reversed by polydatin at 100 mg\/kg. On C2C12 myotubes, polydatin also ameliorated muscle atrophy induced by the CT26 conditioned medium and suppressed STAT3 phosphorylation at the concentration of 200 \u00b5M. Structural features of polydatin in the proteins in the STAT3 pathway were identified through molecular docking simulations. Conclusions: Taken together, polydatin significantly attenuated muscle atrophy in a cancer cachexia model by inhibiting the STAT3 signaling pathway; thus, it might be a promising compound in the development of drug candidates for cancer cachexia therapy.<\/jats:p>","DOI":"10.3390\/nu18040603","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:06:16Z","timestamp":1770905176000},"page":"603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of Polydatin Against Cancer Cachexia by Regulating the STAT3 Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Phuong T.","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-7193","authenticated-orcid":false,"given":"Nalae","family":"Kang","sequence":"additional","affiliation":[{"name":"Jeju Bio Research Center, Korea Institute of Ocean Science & Technology, Jeju 63349, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quynh Xuan Thi","family":"Luong","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meutia Diva","family":"Hakim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5962-3053","authenticated-orcid":false,"given":"Kantawong","family":"Kawalin","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo-Jin","family":"Heo","sequence":"additional","affiliation":[{"name":"Jeju Bio Research Center, Korea Institute of Ocean Science & Technology, Jeju 63349, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-9317","authenticated-orcid":false,"given":"Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Humanitas College, Kyung Hee University, 1732 Deogyeongdae-ro, Yongin 17104, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6090-507X","authenticated-orcid":false,"given":"Taek Kyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Ecological Risk Research Department, Korea Institute of Ocean Science & Technology, Geoje 53201, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9964-0176","authenticated-orcid":false,"given":"Sukchan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e389942","DOI":"10.1200\/EDBK_389942","article-title":"Current Therapeutic Targets in Cancer Cachexia: A Pathophysiologic Approach","volume":"43","author":"Kadakia","year":"2023","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nrc927","article-title":"Cachexia in cancer patients","volume":"2","author":"Tisdale","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.trecan.2018.10.001","article-title":"Cancer Cachexia: More Than Skeletal Muscle Wasting","volume":"4","author":"Schmidt","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_5","first-page":"188359","article-title":"Advances in cancer cachexia: Intersection between affected organs, mediators, and pharmacological interventions","volume":"1873","author":"Siddiqui","year":"2020","journal-title":"BBA Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_7","first-page":"171","article-title":"Signal transducer and activator of transcription 3 signaling as a potential target to treat muscle wasting diseases","volume":"19","author":"Sala","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104871","DOI":"10.1016\/j.phrs.2020.104871","article-title":"Imperatorin alleviates cancer cachexia and prevents muscle wasting via directly inhibiting STAT3","volume":"158","author":"Chen","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/s10753-011-9310-z","article-title":"Anti-inflammpplatory Effect of Resveratrol and Polydatin by In Vitro IL-17 Modulation","volume":"35","author":"Lanzilli","year":"2012","journal-title":"Inflammation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.lfs.2018.11.053","article-title":"Polydatin attenuates spinal cord injury in rats by inhibiting oxidative stress and microglia apoptosis via Nrf2\/HO-1 pathway","volume":"217","author":"Lv","year":"2019","journal-title":"Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ejphar.2014.11.012","article-title":"Polydatin prevents hypertrophy in phenylephrine induced neonatal mouse cardiomyocytes and pressure-overload mouse models","volume":"746","author":"Dong","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.freeradbiomed.2017.03.003","article-title":"Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating CKIP-1 to resist HG-induced up-regulation of FN and ICAM-1 in GMCs and diabetic mice kidneys","volume":"106","author":"Gong","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3390\/nu11030699","article-title":"Twelve-Week Protocatechuic Acid Administration Improves Insulin-Induced and Insulin-Like Growth Factor-1-Induced Vasorelaxation and Antioxidant Activities in Aging Spontaneously Hypertensive Rats","volume":"11","author":"Masodsai","year":"2019","journal-title":"Nutrients"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13846","DOI":"10.1074\/jbc.M115.695528","article-title":"Structural Mimicry of Receptor Interaction by Antagonistic Interleukin-6 (IL-6) Antibodies","volume":"291","author":"Blanchetot","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"132668","DOI":"10.1016\/j.molstruc.2022.132668","article-title":"Genistein: A novel inhibitor of IL-6\/IL-6R interface of the Interleukin-6\u2013mediated STAT3 dependent pathway of carcinogenesis","volume":"1258","author":"Sharma","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1007\/s11030-023-10805-5","article-title":"Taming the cytokine storm: Small molecule inhibitors targeting IL-6\/IL-6\u03b1 receptor","volume":"28","author":"Zia","year":"2024","journal-title":"Mol. Divers."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112428","DOI":"10.1016\/j.ejmech.2020.112428","article-title":"Design, synthesis and biological evaluation of novel potent STAT3 inhibitors based on BBI608 for cancer therapy","volume":"201","author":"Feng","year":"2020","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"128933","DOI":"10.1016\/j.foodchem.2020.128933","article-title":"An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against non structural protein-15 of SARS-CoV-2","volume":"346","author":"Sharma","year":"2021","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kang, N., Kim, E.-A., Heo, S.-Y., and Heo, S.-J. (2023). Structure-Based In Silico Screening of Marine Phlorotannins for Potential Walrus Calicivirus Inhibitor. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115774"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.apsb.2020.02.008","article-title":"Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods","volume":"10","author":"Wu","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hua, Y., Yuan, X., Shen, Y.-H., Wang, J., Azeem, W., Yang, S., Gade, A., Lellahi, S.M., \u00d8yan, A.M., and Ke, X. (2022). Novel STAT3 Inhibitors Targeting STAT3 Dimerization by Binding to the STAT3 SH2 Domain. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.836724"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Webster, J.M., Kempen, L.J.A.P., Hardy, R.S., and Langen, R.C.J. (2020). Inflammation and Skeletal Muscle Wasting During Cachexia. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.597675"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1002\/ptr.7811","article-title":"Cucurbitacin IIb attenuates cancer cachexia induced skeletal muscle atrophy by regulating the IL-6\/STAT3\/FoxO signaling pathway","volume":"37","author":"Wang","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15347354231168369","DOI":"10.1177\/15347354231168369","article-title":"Babao Dan Alleviates Cancer Cachexia in Mice Via Inhibiting IL-6\/STAT3 Signaling Pathway","volume":"22","author":"Qiu","year":"2023","journal-title":"Integr. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1016\/j.clnu.2022.11.009","article-title":"Phytochemicals: A potential therapeutic intervention for the prevention and treatment of cachexia","volume":"41","author":"Zarifi","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E410","DOI":"10.1152\/ajpendo.00039.2012","article-title":"JAK\/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia","volume":"303","author":"Bonetto","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1002\/jcsm.13079","article-title":"Atractylenolide I ameliorates cancer cachexia through inhibiting biogenesis of IL-6 and tumour-derived extracellular vesicles","volume":"13","author":"Fan","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100220","DOI":"10.1074\/jbc.RA120.016645","article-title":"The STAT3 inhibitor Stattic acts independently of STAT3 to decrease histone acetylation and modulate gene expression","volume":"296","author":"Poria","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"He, N., Li, L., Li, R., Zhang, S.-Q., Wu, L.-H., Guan, X., Zhang, Q.-Y., Jiang, T., and Yang, J.-B. (2023). A Novel Ageladine A Derivative Acts as a STAT3 Inhibitor and Exhibits Potential Antitumor Effects. Int. J. Mol. 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