{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:57:09Z","timestamp":1776326229773,"version":"3.50.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Near East University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study investigated the protective effects of verbascoside (VER) against 5-fluorouracil (5-FU)-induced gastrointestinal mucositis in Wistar albino rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The study involved 30 female rats that were equally divided into five groups as follows: Control group, 5-FU group (400\u00a0mg\/kg, IP), VER-only group (0.2\u00a0mg\/kg, IP), 5-FU (400\u00a0mg\/kg, IP)\u2009+\u2009VER (0.2\u00a0mg\/kg, IP) group, and 5-FU (400\u00a0mg\/kg, IP)\u2009+\u2009VER (0.4\u00a0mg\/kg, IP) group. All animals were euthanized four days after 5-FU administration. Gastrointestinal tissues (esophagus, stomach, duodenum, jejunum, ileum, and colon) and blood sera were collected for histopathological and biochemical analyses. Tissue and sera analyses showed that 5-FU caused significant alterations marked by increases in matrix metalloproteinases (MMP-1, -2, -8), alkaline phosphatase (ALP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-\u03b1), and interleukin-1 beta (IL-1\u03b2) levels and decreases in tissue inhibitor of metalloproteinases-1 (TIMP-1), albumin, and total protein levels. VER treatment effectively attenuated these 5-FU-induced changes, with trends toward improved histological outcomes at higher doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings strongly suggest that VER offers significant protection, and these results warrant further investigation into its potential clinical application as an adjunct therapy to mitigate gastrointestinal and other toxicities associated with 5-FU chemotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12032-025-02823-0","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:07:56Z","timestamp":1750082876000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Verbascoside restores gastrointestinal integrity and attenuates inflammation in a rat model of 5-FU-induced mucositis"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-6725","authenticated-orcid":false,"given":"Ugochukwu","family":"Chukwunyere","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3297-5369","authenticated-orcid":false,"given":"Serkan","family":"Say\u0131ner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Mercan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-3679","authenticated-orcid":false,"given":"\u015eule","family":"\u00c7etinel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5489-3420","authenticated-orcid":false,"given":"\u0130hsan","family":"\u00c7ali\u015f","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5175-9290","authenticated-orcid":false,"given":"Ahmet \u00d6zer","family":"Sehirli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"2823_CR1","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1093\/annonc\/mdl332","volume":"18","author":"N Blijlevens","year":"2007","unstructured":"Blijlevens N, Sonis S. Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth factor with multiple biological activities in preventing chemotherapy- and radiotherapy-induced mucositis. Ann Oncol. 2007;18:817\u201326. https:\/\/doi.org\/10.1093\/annonc\/mdl332.","journal-title":"Ann Oncol"},{"key":"2823_CR2","doi-asserted-by":"publisher","unstructured":"Ribeiro SB, de Arau \u0301jo AA, Araujo Junior RF, Brito GA, Leit\u00e3o RC, et al. Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters. PLoS ONE. 2017;12(10):e0186511. https:\/\/doi.org\/10.1371\/journal. pone.0186511.","DOI":"10.1371\/journal"},{"key":"2823_CR3","first-page":"2476","volume":"41","author":"U Chukwunyere","year":"2022","unstructured":"Chukwunyere U, Sehirli AO, Sayiner S, Ceylanli D, Mercan M, et al. Dose-dependent effect of oxytocin on 5-fluorouracil-induced intestinal mucositis in rats. Lat Am J Pharm. 2022;41:2476\u201384.","journal-title":"Lat Am J Pharm"},{"key":"2823_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117612","volume":"252","author":"DC Xiang","year":"2020","unstructured":"Xiang DC, Yang JY, Xu YJ, Zhang S, Li M, Zhu C, Zhang CL, Liu D. Protective effect of Andrographolide on 5-Fu induced intestinal mucositis by regulating p38 MAPK signaling pathway. Life Sci. 2020;252: 117612. https:\/\/doi.org\/10.1016\/j.lfs.2020.117612.","journal-title":"Life Sci"},{"issue":"1","key":"2823_CR5","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1186\/s12885-021-09057-z","volume":"21","author":"J Yoneda","year":"2021","unstructured":"Yoneda J, Nishikawa S, Kurihara S. Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model. BMC Cancer. 2021;21(1):1343. https:\/\/doi.org\/10.1186\/s12885-021-09057-z.","journal-title":"BMC Cancer"},{"issue":"5","key":"2823_CR6","doi-asserted-by":"publisher","first-page":"4055","DOI":"10.1007\/s11033-022-07384-3","volume":"49","author":"U Chukwunyere","year":"2022","unstructured":"Chukwunyere U, Mercan M, Sehirli AO, Abacioglu N. Possible cytoprotective mechanisms of oxytocin against 5-fluorouracil-induced gastrointestinal mucositis. Mol Bio Rep. 2022;49(5):4055\u20139. https:\/\/doi.org\/10.1007\/s11033-022-07384-3.","journal-title":"Mol Bio Rep"},{"issue":"10","key":"2823_CR7","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.3390\/nu11102322","volume":"11","author":"JA Pic\u00f3-Monllor","year":"2019","unstructured":"Pic\u00f3-Monllor JA, Mingot-Ascencao JM. Search and selection of probiotics that improve mucositis symptoms in oncologic patients. A systematic review. Nutrients. 2019;11(10):2322. https:\/\/doi.org\/10.3390\/nu11102322.","journal-title":"Nutrients"},{"issue":"6","key":"2823_CR8","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1007\/s00520-006-0066-1","volume":"14","author":"A Barasch","year":"2006","unstructured":"Barasch A, Elad S, Altman A, Damato K, Epstein J. Antimicrobials, mucosal coating agents, anesthetics, analgesics, and nutritional supplements for alimentary tract mucositis. Support Care Cancer. 2006;14(6):528\u201332. https:\/\/doi.org\/10.1007\/s00520-006-0066-1.","journal-title":"Support Care Cancer"},{"key":"2823_CR9","doi-asserted-by":"publisher","unstructured":"Eryani K, Enciso R. Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: a systematic review and meta-analyses. Support Care Cancer. 2022;30(11):8689\u2013703. https:\/\/doi.org\/10.1007\/s00520-022-07190-4","DOI":"10.1007\/s00520-022-07190-4"},{"key":"2823_CR10","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1007\/s00520-019-04888-w","volume":"27","author":"A Ariyawardana","year":"2019","unstructured":"Ariyawardana A, Cheng KKF, Kandwal A, et al. Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer. 2019;27:3985\u201395. https:\/\/doi.org\/10.1007\/s00520-019-04888-w.","journal-title":"Support Care Cancer"},{"issue":"5","key":"2823_CR11","doi-asserted-by":"publisher","first-page":"637","DOI":"10.4274\/tjps.galenos.2021.36599","volume":"18","author":"H \u015eenol","year":"2021","unstructured":"\u015eenol H, Tulay P, Erg\u00f6ren M\u00c7, Hano\u011flu A, \u00c7al\u0131\u015f \u0130, Mocan G. Cytotoxic Effects of Verbascoside on MCF-7 and MDA-MB-231. Turk J Pharm Sci. 2021;18(5):637\u201344. https:\/\/doi.org\/10.4274\/tjps.galenos.2021.36599.","journal-title":"Turk J Pharm Sci"},{"issue":"1","key":"2823_CR12","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1186\/s12885-020-07447-3","volume":"20","author":"D Ma","year":"2020","unstructured":"Ma D, Wang J, Liu L, Chen M, Wang Z. Acteoside as a potential therapeutic option for primary hepatocellular carcinoma: a preclinical study. BMC Cancer. 2020;20(1):936. https:\/\/doi.org\/10.1186\/s12885-020-07447-3.","journal-title":"BMC Cancer"},{"issue":"6","key":"2823_CR13","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/ptr.990","volume":"16","author":"P Akbay","year":"2002","unstructured":"Akbay P, Calis I, Undeger U, Basaran N, Basaran AA. In vitro immunomodulatory activity of verbascoside from Nepeta ucrainica L. Phytother Res. 2002;16(6):593\u20135. https:\/\/doi.org\/10.1002\/ptr.990.","journal-title":"Phytother Res"},{"key":"2823_CR14","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.14765","volume":"11","author":"Y Mao","year":"2023","unstructured":"Mao Y, Yu J, Da J, Yu F, Zha Y. Acteoside alleviates UUO-induced inflammation and fibrosis by regulating the HMGN1\/TLR4\/TREM1 signaling pathway. PeerJ. 2023;11: e14765. https:\/\/doi.org\/10.7717\/peerj.14765.","journal-title":"PeerJ"},{"key":"2823_CR15","doi-asserted-by":"publisher","unstructured":"Lenoir L, Rossary A, Joubert-Zakeyh J, Vergnaud-Gauduchon J, Farges MC, Fraisse D, Texier O, Lamaison JL, Vasson MP, Felgines C. Lemon verbena infusion consumption attenuates oxidative stress in dextran sulfate sodium-induced colitis in the rat. Dig Dis Sci. 2011;56:3534\u201345. https:\/\/doi.org\/10.1007\/s10620-011-1784-x","DOI":"10.1007\/s10620-011-1784-x"},{"key":"2823_CR16","doi-asserted-by":"publisher","unstructured":"Vertuani S, Beghelli E, Scalambra E, Malisardi G, Copetti S, Dal Toso R, Baldisserotto A, Manfredini S. Activity and stability studies of verbascoside, a novel antioxidant, in dermo-cosmetic and pharmaceutical topical formulations. Molecules. 2011;16:7068\u201380. https:\/\/doi.org\/10.3390\/molecules16087068","DOI":"10.3390\/molecules16087068"},{"issue":"1","key":"2823_CR17","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1080\/13880209.2021.1933085","volume":"59","author":"L Han","year":"2021","unstructured":"Han L, Xiang S, Rong B, Liang Y, Zhao S. Verbascoside attenuates experimental varicocele-induced damage to testes and sperm levels through up-regulation of the hypothalamus-pituitary-gonadal (HPG) axis. Pharm Biol. 2021;59(1):715\u201322. https:\/\/doi.org\/10.1080\/13880209.2021.1933085.","journal-title":"Pharm Biol"},{"issue":"7","key":"2823_CR18","doi-asserted-by":"publisher","first-page":"548","DOI":"10.5152\/tjg.2021.19747","volume":"32","author":"AN De\u011fer","year":"2021","unstructured":"De\u011fer AN, \u00d6zyi\u011fit F, Ko\u00e7ak FE, Bayhan Z, Zeren S, Ar\u0131k \u00d6, De\u011fer H. Corrective effect of verbascoside on histomorphological differences and oxidative stress in colon mucosa of rats in which colon ischemia-reperfusion injury was induced. Turk J Gastroenterol. 2021;32(7):548\u20139. https:\/\/doi.org\/10.5152\/tjg.2021.19747.","journal-title":"Turk J Gastroenterol"},{"key":"2823_CR19","doi-asserted-by":"publisher","unstructured":"Funari CS, Gullo FP, Napolitano A, Carneiro RL, Mendes-Giannini MJ, Fusco-Almeida AM, Piacente S, Pizza C, Silva DH. Chemical and antifungal investigations of six Lippia species (Verbenaceae) from Brazil. Food Chem. 2012;135:2086\u201394. https:\/\/doi.org\/10.1016\/j.foodchem.2012.06.077","DOI":"10.1016\/j.foodchem.2012.06.077"},{"key":"2823_CR20","doi-asserted-by":"publisher","unstructured":"Maquiaveli CDC, Rochetti AL, Fukumasu H, Vieira PC, da Silva ER. Antileishmanial activity of verbascoside: Selective arginase inhibition of intracellular amastigotes of Leishmania (Leishmania) amazonensis with resistance induced by LPS plus IFN-\u03b3. Biochem Pharmacol. 2017;127:28\u201333. https:\/\/doi.org\/10.1016\/j.bcp.2016.12.018","DOI":"10.1016\/j.bcp.2016.12.018"},{"key":"2823_CR21","doi-asserted-by":"publisher","first-page":"62349","DOI":"10.1155\/2013\/623497","volume":"2013","author":"M Chen","year":"2013","unstructured":"Chen M, Bin Huang YZ, Yang X, Wu Y, Liu B, Yuan Y, Zhang G. Evaluation of the antitumor activity by Ni nanoparticles with verbascoside. J Nanomater. 2013;2013:62349. https:\/\/doi.org\/10.1155\/2013\/623497.","journal-title":"J Nanomater"},{"key":"2823_CR22","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1186\/1471-2407-14-747","volume":"14","author":"L Zhou","year":"2014","unstructured":"Zhou L, Feng Y, Jin Y, Liu X, Sui H, Chai N, Chen X, Liu N, Ji Q, Wang Y, Li Q. Verbascoside promotes apoptosis by regulating HIPK2-p53 signaling in human colorectal cancer. BMC Cancer. 2014;14:747. https:\/\/doi.org\/10.1186\/1471-2407-14-747.","journal-title":"BMC Cancer"},{"key":"2823_CR23","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1002\/ijc.31378","volume":"143","author":"Y Zhang","year":"2018","unstructured":"Zhang Y, Yuan Y, Wu H, Xie Z, Wu Y, Song X, Wang J, Shu W, Xu J, Liu B, Wan L, Yan Y, Ding X, Shi X, Pan Y, Li X, Yang J, Zhao X, Wang L. Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma. Int J Cancer. 2018;143:980\u201391. https:\/\/doi.org\/10.1002\/ijc.31378.","journal-title":"Int J Cancer"},{"key":"2823_CR24","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1159\/000491067","volume":"47","author":"WQ Jia","year":"2018","unstructured":"Jia WQ, Wang ZT, Zou MM, Lin JH, Li YH, Zhang L, Xu RX. Verbascoside inhibits glioblastoma cell proliferation, migration and \u0131nvasion while promoting apoptosis through upregulation of protein tyrosine phosphatase shp-1 and \u0131nhibition of stat3 phosphorylation. Cell Physiol Biochem. 2018;47:1871\u201382. https:\/\/doi.org\/10.1159\/000491067.","journal-title":"Cell Physiol Biochem"},{"issue":"4","key":"2823_CR25","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1210\/endo-123-4-1837","volume":"123","author":"DJ Brillon","year":"1998","unstructured":"Brillon DJ, Henry RR, Klein HH, Olefsky JM, Freidenberg GR. Functional and structural differences in human and rat-derived insulin receptors: characterization of the beta-subunit kinase activity. Endocrinology. 1998;123(4):1837\u201347. https:\/\/doi.org\/10.1210\/endo-123-4-1837.","journal-title":"Endocrinology"},{"key":"2823_CR26","unstructured":"\u00c7al\u0131\u015f \u0130, Saraco\u011flu \u0130, Ers\u00f6z T, K\u0131rm\u0131z\u0131bekmez H, Yal\u00e7\u0131n FN, Harput \u015e. Chemotaxonomy of Turkish Phlomis L. (Lamiaceae) Genus. The Scientific and Technological Research Council of Turkey Project Number: SBAG-2304; 2004."},{"issue":"2","key":"2823_CR27","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.3892\/ol.2018.8893","volume":"16","author":"SH Kim","year":"2018","unstructured":"Kim SH, Chun HJ, Choi HS, Kim ES, Keum B, Seo YS, Jeen YT, Lee HS, Um SH, Kim CD. Ursodeoxycholic acid attenuates 5-fluorouracil-induced mucositis in a rat model. Oncol Lett. 2018;16(2):2585\u201390. https:\/\/doi.org\/10.3892\/ol.2018.8893.","journal-title":"Oncol Lett"},{"key":"2823_CR28","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/s0076-6879(78)52032-6","volume":"53","author":"JA Beuge","year":"1978","unstructured":"Beuge JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;53:302\u201311. https:\/\/doi.org\/10.1016\/s0076-6879(78)52032-6.","journal-title":"Methods Enzymol"},{"key":"2823_CR29","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.cyto.2012.10.003","volume":"61","author":"PM Soares","year":"2013","unstructured":"Soares PM, Mota JMS, Souza EP, Justino PF, Franco AX, Cunha FQ, Souza MH. Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4. Cytokine. 2013;61:46\u20139. https:\/\/doi.org\/10.1016\/j.cyto.2012.10.003.","journal-title":"Cytokine"},{"key":"2823_CR30","doi-asserted-by":"publisher","unstructured":"MacPherson B, Pfeiffer C. Experimental production of diffuse colitis in rats. Digestion. 1978;17:135\u201350. https:\/\/doi.org\/10.1159\/000198104","DOI":"10.1159\/000198104"},{"issue":"5","key":"2823_CR31","doi-asserted-by":"publisher","DOI":"10.1590\/0100-6991e-20181968","volume":"45","author":"AD Medeiros","year":"2018","unstructured":"Medeiros AD, Azevedo \u00cdM, Lima ML, Ara\u00fajo Filho I, Moreira MD. Effects of simvastatin on 5-fluorouracil-induced gastrointestinal mucositis in rats. Rev Col Bras Cir. 2018;45(5): e1968. https:\/\/doi.org\/10.1590\/0100-6991e-20181968.","journal-title":"Rev Col Bras Cir"},{"key":"2823_CR32","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.apjtb.2017.06.013","volume":"7","author":"V Gelen","year":"2017","unstructured":"Gelen V, \u015eeng\u00fcl E, Gedikli S, Atila G, Uslu H, Makav M. The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats. Asian Pac J Trop Biomed. 2017;7:647\u201353. https:\/\/doi.org\/10.1016\/j.apjtb.2017.06.013.","journal-title":"Asian Pac J Trop Biomed"},{"key":"2823_CR33","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.biopha.2018.07.029","volume":"106","author":"S Zhang","year":"2018","unstructured":"Zhang S, Liu Y, Xiang D, Yang J, Liu D, Ren X, Zhang C. Assessment of dose- response relationship of 5-fluorouracil to murine intestinal injury. Biomed Pharmacother. 2018;106:910\u20136. https:\/\/doi.org\/10.1016\/j.biopha.2018.07.029.","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"2823_CR34","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.curtheres.2011.11.003","volume":"72","author":"D Tung","year":"2011","unstructured":"Tung D, Cheung PH, Tudor G, Booth C, Saha S. In vivo effects of immunomodulators in a murine model of Fluorouracil-induced mucositis. Curr Ther Res. 2011;72(6):262\u201372. https:\/\/doi.org\/10.1016\/j.curtheres.2011.11.003.","journal-title":"Curr Ther Res"},{"key":"2823_CR35","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1007\/BF02969425","volume":"29","author":"JH Lee","year":"2006","unstructured":"Lee JH, Lee JY, Kang HS, Jeong CH, Moon H, Whang WK, et al. The effect of acteoside on histamine release and arachidonic acid release in RBL-2H3 mast cells. Arch Pharm Res. 2006;29:508\u201313. https:\/\/doi.org\/10.1007\/BF02969425.","journal-title":"Arch Pharm Res"},{"key":"2823_CR36","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s00210-009-0400-5","volume":"380","author":"E Mazzon","year":"2009","unstructured":"Mazzon E, Esposito E, Di Paola R, Riccardi L, Caminiti R, Dal Toso R, et al. Effects of verbascoside biotechnologically produced by Syringa vulgaris plant cell cultures in rodent model of colitis. Naunyn Schmiedebergs Arch Pharmacol. 2009;380:79\u201394. https:\/\/doi.org\/10.1007\/s00210-009-0400-5.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"2823_CR37","doi-asserted-by":"publisher","unstructured":"Galli A, Marciani P, Marku A, Ghislanzoni S, Bertuzzi F, Rossi R, Di Giancamillo A, Castagna M, Perego C. Verbascoside protects pancreatic \u03b2-cells against ER-stress. Biomedicines. 2020;8(12):582. https:\/\/doi.org\/10.3390\/biomedicines8120582","DOI":"10.3390\/biomedicines8120582"},{"key":"2823_CR38","doi-asserted-by":"publisher","unstructured":"Wang C, Cai X, Wang R, Zhai S, Zhang Y, Hu W, Zhang Y, Wang D. Neuroprotective effects of verbascoside against Alzheimer's disease via the relief of endoplasmic reticulum stress in A\u03b2-exposed U251 cells and APP\/PS1 mice. J Neuroinflammation. 2020;17(1):309. https:\/\/doi.org\/10.1186\/s12974-020-01976-1","DOI":"10.1186\/s12974-020-01976-1"},{"key":"2823_CR39","doi-asserted-by":"publisher","unstructured":"Hsieh PF, Yu CC, Chu PM, Hsieh PL. Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC\/HMGB1\/RAGE\/NF\u03baB Pathway. Antioxidants (Basel). 2021;10(9):1445. https:\/\/doi.org\/10.3390\/antiox10091445","DOI":"10.3390\/antiox10091445"},{"issue":"6","key":"2823_CR40","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.2527\/jas.2014-8607","volume":"93","author":"A Di Giancamillo","year":"2015","unstructured":"Di Giancamillo A, Rossi R, Pastorelli G, Deponti D, Carollo V, Casamassima D, Domeneghini C, Corino C. The effects of dietary verbascoside on blood and liver oxidative stress status induced by a high n-6 polyunsaturated fatty acids diet in piglets. J Anmi Sci. 2015;93(6):2849\u201359. https:\/\/doi.org\/10.2527\/jas.2014-8607.","journal-title":"J Anmi Sci"},{"issue":"2","key":"2823_CR41","doi-asserted-by":"publisher","first-page":"102","DOI":"10.2174\/1871530314666140407152347","volume":"14","author":"AG D'Alessandro","year":"2014","unstructured":"D\u2019Alessandro AG, Casamassima D, Jirillo F, Martemucci G. Effects of verbascoside administration on the blood parameters and oxidative status in jennies and their suckling foals: potential improvement of milk for human use. Endocr Metab Immune Disord Drug Targets. 2014;14(2):102\u201312. https:\/\/doi.org\/10.2174\/1871530314666140407152347.","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"2823_CR42","doi-asserted-by":"publisher","unstructured":"\u015eehirli A\u00d6, Sayiner S, Savtekin G, Velio\u011flu-\u00d6\u011f\u00fcnc\u0327 A. Protective effect of bromelain on corrosive burn in rats. Burns. 2021;47(6):1352\u20138. https:\/\/doi.org\/10.1016\/j.burns.2020.12.006","DOI":"10.1016\/j.burns.2020.12.006"},{"key":"2823_CR43","doi-asserted-by":"publisher","unstructured":"Sun L, Li Y, Shi J, Wang X, Wang X. Protective effects of ligustrazine on ischemia-reperfusion injury in rat kidneys. Microsurgery. 2002;22:343\u20136. https:\/\/doi.org\/10.1002\/micr.10058","DOI":"10.1002\/micr.10058"},{"key":"2823_CR44","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/bcpt.12793","volume":"21","author":"N Hamouda","year":"2017","unstructured":"Hamouda N, Sano T, Oikawa Y, Ozaki T, Shimakawa M, Matsumoto K, et al. Apoptosis, dysbiosis and expression of inflammatory cytokines are sequential events in the development of 5-fluorouracil-induced intestinal Mucositis in mice. Basic Clin Pharmacol Toxicol. 2017;21:159\u201368. https:\/\/doi.org\/10.1111\/bcpt.12793.","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"4","key":"2823_CR45","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1159\/000486958","volume":"175","author":"Y Li","year":"2018","unstructured":"Li Y, Yu H, Jin Y, Li M, Qu C. Verbascoside Alleviates Atopic Dermatitis-Like Symptoms in Mice via Its Potent Anti-Inflammatory Effect. Int Arch Allergy Immunol. 2018;175(4):220\u201330. https:\/\/doi.org\/10.1159\/000486958.","journal-title":"Int Arch Allergy Immunol"},{"key":"2823_CR46","doi-asserted-by":"publisher","unstructured":"Fan Y, Zhang K. Verbascoside inhibits the progression of atherosclerosis in high fat diet induced atherosclerosis rat model. J Physiol Pharmacol. 2021;72(3). https:\/\/doi.org\/10.26402\/jpp.2021.3.03","DOI":"10.26402\/jpp.2021.3.03"},{"issue":"5","key":"2823_CR47","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.2353\/ajpath.2009.080705","volume":"175","author":"L Zheng","year":"2009","unstructured":"Zheng L, Amano K, Iohara K, et al. Matrix metalloproteinase-3 accelerates wound healing following dental pulp injury. Am J Pathol. 2009;175(5):1905\u201314. https:\/\/doi.org\/10.2353\/ajpath.2009.080705.","journal-title":"Am J Pathol"},{"issue":"1","key":"2823_CR48","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1177\/1534734609331596","volume":"8","author":"EA Rayment","year":"2009","unstructured":"Rayment EA, Upton Z. Finding the culprit: a review of the influences of proteases on the chronic wound environment. Int J Low Extrem Wounds. 2009;8(1):19\u201327. https:\/\/doi.org\/10.1177\/1534734609331596.","journal-title":"Int J Low Extrem Wounds"},{"key":"2823_CR49","first-page":"79","volume":"68","author":"T Sano","year":"2017","unstructured":"Sano T, Utsumi D, Amagase K, Matsumoto K, Tominaga M, Higuchi K, et al. Lafutidine, a histamine H2 receptor antagonist with mucosal protective properties, attenuates 5-fluorouracil-induced intestinal mucositis in mice through activation of extrinsic primary afferent neurons. J Physiol Pharmacol. 2017;68:79\u201390.","journal-title":"J Physiol Pharmacol"},{"issue":"12","key":"2823_CR50","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3389\/fnmol.2019.00220","volume":"20","author":"BE Knight","year":"2019","unstructured":"Knight BE, Kozlowski N, Havelin J, King T, Crocker SJ, Young EE, Baumbauer KM. TIMP-1 Attenuates the Development of Inflammatory Pain Through MMP-Dependent and Receptor-Mediated Cell Signaling Mechanisms. Front Mol Neurosci. 2019;20(12):220. https:\/\/doi.org\/10.3389\/fnmol.2019.00220.","journal-title":"Front Mol Neurosci"},{"key":"2823_CR51","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.dld.2007.05.010","volume":"39","author":"M Meijer","year":"2007","unstructured":"Meijer M, Mieremet-Ooms M, Van Der Zon A, Van Duijn W, Van Hogezand R, Sier C, Hommes D, Lamers C, Verspaget H. Increased mucosal matrix metalloproteinase-1, -2, -3 and -9 activity in patients with inflammatory bowel disease and the relation with Crohn\u2019s disease phenotype. Dig Liver Dis. 2007;39:733\u20139. https:\/\/doi.org\/10.1016\/j.dld.2007.05.010.","journal-title":"Dig Liver Dis"},{"key":"2823_CR52","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/s00384-008-0452-x","volume":"23","author":"A Solberg","year":"2008","unstructured":"Solberg A, Holmdahl L, Falk P, Palmgren I, Ivarsson M. A local imbalance between MMP and TIMP may have an implication on the severity and course of appendicitis. Int J Colorectal Dis. 2008;23:611\u20138. https:\/\/doi.org\/10.1007\/s00384-008-0452-x.","journal-title":"Int J Colorectal Dis"},{"key":"2823_CR53","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.coph.2004.06.005","volume":"4","author":"S Pender","year":"2004","unstructured":"Pender S, MacDonald T. Matrix metalloproteinases and the gut- new roles for old enzymes. Curr Opin Pharmacol. 2004;4:546\u201350. https:\/\/doi.org\/10.1016\/j.coph.2004.06.005.","journal-title":"Curr Opin Pharmacol"},{"key":"2823_CR54","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1161\/01.res.0000070112.80711.3d","volume":"92","author":"R Visse","year":"2003","unstructured":"Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003;92:827\u201339. https:\/\/doi.org\/10.1161\/01.res.0000070112.80711.3d.","journal-title":"Circ Res"},{"issue":"4","key":"2823_CR55","doi-asserted-by":"publisher","first-page":"3237","DOI":"10.1007\/s11033-022-07158-x","volume":"49","author":"K Bilginaylar","year":"2022","unstructured":"Bilginaylar K, Aykac A, Sayiner S, \u00d6zkayalar H, \u015eehirli A\u00d6. Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats. Mol Bio Rep. 2022;49(4):3237\u201345. https:\/\/doi.org\/10.1007\/s11033-022-07158-x.","journal-title":"Mol Bio Rep"},{"key":"2823_CR56","doi-asserted-by":"publisher","first-page":"7939","DOI":"10.1007\/s00210-024-03144-1","volume":"397","author":"M Safari Samangani","year":"2024","unstructured":"Safari Samangani M, Mehri S, Aminifard T, et al. Effect of verbascoside against acute kidney injury induced by rhabdomyolysis in rats. Naunyn-Schmiedeberg\u2019s Arch Pharmacol. 2024;397:7939\u201350. https:\/\/doi.org\/10.1007\/s00210-024-03144-1.","journal-title":"Naunyn-Schmiedeberg's Arch Pharmacol"},{"key":"2823_CR57","doi-asserted-by":"publisher","unstructured":"Zhang G, Yu F, Dong R, Yu J, Luo M, Zha Y. Verbascoside alleviates renal fibrosis in unilateral ureteral obstruction rats by inhibiting macrophage infiltration. Iran J Basic Med Sci. 2021;24(6):752\u20139. https:\/\/doi.org\/10.22038\/ijbms.2021.52759.11903","DOI":"10.22038\/ijbms.2021.52759.11903"},{"issue":"1","key":"2823_CR58","doi-asserted-by":"publisher","first-page":"23241","DOI":"10.1038\/s41598-021-01969-x","volume":"11","author":"MM Oliveira","year":"2021","unstructured":"Oliveira MM, de Ara\u00fajo AA, Ribeiro SB, de Sales Mota PC, Marques VB, et al. Losartan improves intestinal mucositis induced by 5-fluorouracil in mice. Sci Rep. 2021;11(1):23241. https:\/\/doi.org\/10.1038\/s41598-021-01969-x.","journal-title":"Sci Rep"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-02823-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-025-02823-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-02823-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T07:22:24Z","timestamp":1776324144000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-025-02823-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,16]]},"references-count":58,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["2823"],"URL":"https:\/\/doi.org\/10.1007\/s12032-025-02823-0","relation":{},"ISSN":["1559-131X"],"issn-type":[{"value":"1559-131X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,16]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2025","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised: The second sentence in funding section should be changed from \u201cThe authors received no financial support for this research, authorship, and\/or publication of this article.\" to \"The authors received no financial support for this research and\/or authorship of this article\". It is now corrected.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"We declare that this manuscript is original, has not been published before, and is not currently being considered for publication elsewhere.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"This study was approved by the Near East University Animal Ethics Committee.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"267"}}