{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:40:18Z","timestamp":1791862818800,"version":"4.3.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis, an inflammatory bowel disease, is characterized by a status of oxidative stress and inflammation. Rutin is a natural flavonoid with many pharmacological activities and its role in acetic acid-induced ulcerative colitis through the high mobility group B1 (HMGB1)\/ toll-like receptor-4 (TLR4)\/ myeloid differentiation primary response protein 88 (MYD88)\/ nuclear factor-kB (NF-kB) signaling pathway needs to be explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Four experimental groups were divided into control group, rutin group: treated with 100\u00a0mg\/kg\/day rutin orally for 10\u00a0days, acetic acid (AA) group: given intracolonic instillation of AA to induce ulcerative colitis, and acetic acid with rutin treatment (AA\/Rutin) group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Acetic acid caused a marked increase in the colon weight\/length ratio and induced colonic histopathological changes, leading to a marked rise in the colonic histopathological scores. Acetic acid exhibited a significant rise in LDH and CRP serum levels as well as TOS colonic levels, accompanied by a marked decline in TAS colonic contents compared to the control group. Moreover, AA-induced activation of the HMGB1\/TLR4\/MYD88\/NF-kB signaling pathway. Rutin demonstrated a significant decrease in the colon weight\/length ratio, ameliorated the colonic histopathological changes induced by AA, and exhibited a marked decline in the colonic histopathological scores. Rutin showed a significant decrease in serum LDH, and CRP levels as well as colonic TOS contents when compared with the AA group. Rutin suppressed the colonic activation of the HMGB1\/TLR4\/MYD88\/NF-kB signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Rutin could be a promising coloprotective agent against AA-induced ulcerative colitis by targeting the HMGB1\/TLR4\/MYD88\/NF-kB signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/toxres\/tfae108","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T04:47:14Z","timestamp":1721882834000},"source":"Crossref","is-referenced-by-count":10,"title":["Rutin mitigates acetic acid-induced ulcerative colitis: novel coloprotective mechanism"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9487-3456","authenticated-orcid":false,"given":"Iman O","family":"Sherif","sequence":"first","affiliation":[{"name":"Emergency Hospital , Faculty of Medicine, , El Gomhoria Street, Mansoura 35516 , Egypt"},{"name":"Mansoura University , Faculty of Medicine, , El Gomhoria Street, Mansoura 35516 , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5285-2155","authenticated-orcid":false,"given":"Nora H","family":"Al-Shaalan","sequence":"additional","affiliation":[{"name":"Princess Nourah bint Abdulrahman University Chemistry Department, College of Science, , Airport Road, P.O. Box 84428, Riyadh 11671 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3510-0197","authenticated-orcid":false,"given":"Walaa F","family":"Awadin","sequence":"additional","affiliation":[{"name":"Pathology Department , Faculty of Veterinary Medicine, , El Gomhoria Street, Mansoura 35516 , Egypt"},{"name":"Mansoura University , Faculty of Veterinary Medicine, , El Gomhoria Street, Mansoura 35516 , Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"issue":"1","key":"2024080708090549500_ref1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10787-016-0305-0","article-title":"Implication of Nrf2\/HO-1 pathway in the coloprotective effect of coenzyme Q10 against experimentally induced ulcerative colitis","volume":"25","author":"Khodir","year":"2017","journal-title":"Inflammopharmacology"},{"issue":"8","key":"2024080708090549500_ref2","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1111\/jphp.12408","article-title":"Spray-dried extract of Phyllanthus niruri L. reduces mucosal damage in rats with intestinal inflammation","volume":"67","author":"Nunes de Melo","year":"2015","journal-title":"J Pharm Pharmacol"},{"issue":"23","key":"2024080708090549500_ref3","doi-asserted-by":"crossref","first-page":"29615","DOI":"10.1007\/s11356-021-12716-0","article-title":"Graviola mitigates acetic acid\u2013induced ulcerative colitis in rats: insight on apoptosis and Wnt\/Hh signaling crosstalk","volume":"28","author":"Helal","year":"2021","journal-title":"Environ Sci Pollut Res"},{"issue":"11","key":"2024080708090549500_ref4","first-page":"2765","article-title":"Green pea (Pisum sativum L.) hull polyphenol extracts ameliorate dss-induced colitis through keap1\/nrf2 pathway and gut microbiota modulation","volume":"10","author":"Guo","year":"2021","journal-title":"Food Secur"},{"key":"2024080708090549500_ref5","doi-asserted-by":"crossref","first-page":"113651","DOI":"10.1016\/j.biopha.2022.113651","article-title":"Diacetylrhein, an anthraquinone antiarthritic agent, suppresses dextran sodium sulfate-induced inflammation in rats: a possible mechanism for a protective effect against ulcerative colitis","volume":"154","author":"Zohny","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"2024080708090549500_ref6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.21608\/mjmr.2021.242022","article-title":"Possible protective effects of sulfasalazine on acetic acid-induced colitis in rats through its effect on oxidative stress and proinflammatory mediators","volume":"32","author":"Abdelmonaem","year":"2021","journal-title":"Minia J Med Res"},{"key":"2024080708090549500_ref7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jff.2014.12.041","article-title":"The small intestinal mucosa acts as a rutin reservoir to extend flavonoid anti-inflammatory activity in experimental ileitis and colitis","volume":"13","author":"Mascaraque","year":"2015","journal-title":"J Funct Foods"},{"issue":"3","key":"2024080708090549500_ref8","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.bcp.2004.10.015","article-title":"Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression","volume":"69","author":"Kwon","year":"2005","journal-title":"Biochem Pharmacol"},{"issue":"18","key":"2024080708090549500_ref9","doi-asserted-by":"crossref","first-page":"8492","DOI":"10.1039\/D1FO01557E","article-title":"Rutin prevents inflammation-associated colon damage via inhibiting the p38\/MAPKAPK2 and PI3K\/Akt\/GSK3\u03b2\/NF-\u03baB signalling axes and enhancing splenic Tregs in DSS-induced murine chronic colitis","volume":"12","author":"Sharma","year":"2021","journal-title":"Food Funct"},{"issue":"2","key":"2024080708090549500_ref10","first-page":"83","article-title":"Protective effect of Emblica officinalis fruit extract on acetic acid induced colitis in rats","volume":"4","author":"Deshmukh","year":"2010","journal-title":"J Herb Med Toxicol"},{"issue":"12","key":"2024080708090549500_ref11","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","article-title":"A new automated colorimetric method for measuring total oxidant status","volume":"38","author":"Erel","year":"2005","journal-title":"Clin Biochem"},{"issue":"4","key":"2024080708090549500_ref12","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","article-title":"A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation","volume":"37","author":"Erel","year":"2004","journal-title":"Clin Biochem"},{"key":"2024080708090549500_ref13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/8785497","article-title":"Acetic acid-induced ulcerative colitis in Sprague Dawley rats is suppressed by hydroethanolic extract of Cordia vignei leaves through reduced serum levels of TNF-\u03b1 and IL-6","volume":"2020","author":"Owusu","year":"2020","journal-title":"Int J Chronic Dis"},{"issue":"13","key":"2024080708090549500_ref14","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.3390\/molecules27134139","article-title":"Sinapic acid ameliorates acetic acid-induced ulcerative colitis in rats by suppressing inflammation, oxidative stress, and apoptosis","volume":"27","author":"Shahid","year":"2022","journal-title":"Molecules"},{"key":"2024080708090549500_ref15","doi-asserted-by":"crossref","first-page":"103833","DOI":"10.1016\/j.etap.2022.103833","article-title":"Preventive empagliflozin activity on acute acetic acid-induced ulcerative colitis in rats via modulation of SIRT-1\/PI3K\/AKT pathway and improving colon barrier","volume":"91","author":"Zaghloul","year":"2022","journal-title":"Environ Toxicol Pharmacol"},{"key":"2024080708090549500_ref16","doi-asserted-by":"crossref","first-page":"121820","DOI":"10.1016\/j.lfs.2023.121820","article-title":"Eicosapentaenoic acid mitigates ulcerative colitis-induced by acetic acid through modulation of NF-\u03baB and TGF-\u03b2\/EGFR signaling pathways","volume":"327","author":"El Mahdy","year":"2023","journal-title":"Life Sci"},{"issue":"Pt B","key":"2024080708090549500_ref17","doi-asserted-by":"crossref","first-page":"108289","DOI":"10.1016\/j.intimp.2021.108289","article-title":"A novel role of pirfenidone in attenuation acetic acid induced ulcerative colitis by modulation of TGF-\u03b21\/JNK1 pathway","volume":"101","author":"Antar","year":"2021","journal-title":"Int Immunopharmacol"},{"issue":"5","key":"2024080708090549500_ref18","doi-asserted-by":"crossref","first-page":"329","DOI":"10.2131\/jts.43.329","article-title":"Protective effects of rutin on lipopolysaccharide-induced heart injury in mice","volume":"43","author":"Xianchu","year":"2018","journal-title":"J Toxicol Sci"},{"issue":"1-2","key":"2024080708090549500_ref19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11010-016-2767-1","article-title":"Cardioprotective effects of rutin via alteration in TNF-\u03b1, CRP, and BNP levels coupled with antioxidant effect in STZ-induced diabetic rats","volume":"420","author":"Saklani","year":"2016","journal-title":"Mol Cell Biochem"},{"issue":"3","key":"2024080708090549500_ref20","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3109\/08923973.2015.1021357","article-title":"Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats","volume":"37","author":"El Morsy","year":"2015","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"2024080708090549500_ref21","doi-asserted-by":"crossref","first-page":"111902","DOI":"10.1016\/j.biopha.2021.111902","article-title":"Canagliflozin, an SGLT-2 inhibitor, ameliorates acetic acid-induced colitis in rats through targeting glucose metabolism and inhibiting NOX2","volume":"141","author":"Morsy","year":"2021","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"2024080708090549500_ref22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-016-1069-1","article-title":"Rutin attenuates intestinal toxicity induced by methotrexate linked with anti-oxidative and anti-inflammatory effects","volume":"16","author":"Gautam","year":"2016","journal-title":"BMC Complement Altern Med"},{"issue":"1","key":"2024080708090549500_ref23","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1600-065X.2007.00574.x","article-title":"High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity","volume":"220","author":"Bianchi","year":"2007","journal-title":"Immunol Rev"},{"issue":"8","key":"2024080708090549500_ref24","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1177\/1753425916669862","article-title":"HMGB1 exacerbates experimental mouse colitis by enhancing innate lymphoid cells 3 inflammatory responses via promoted IL-23 production","volume":"22","author":"Chen","year":"2016","journal-title":"Innate Immun"},{"key":"2024080708090549500_ref25","doi-asserted-by":"crossref","first-page":"119295","DOI":"10.1016\/j.lfs.2021.119295","article-title":"Linagliptin mitigates experimental inflammatory bowel disease in rats by targeting inflammatory and redox signaling","volume":"273","author":"Arab","year":"2021","journal-title":"Life Sci"},{"issue":"1","key":"2024080708090549500_ref26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-018-1078-8","article-title":"Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II","volume":"15","author":"Zhang","year":"2018","journal-title":"J Neuroinflammation"},{"issue":"2","key":"2024080708090549500_ref27","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1007\/s10753-020-01354-2","article-title":"Luteolin relieved DSS-induced colitis in mice via HMGB1-TLR-NF-\u03baB signaling pathway","volume":"44","author":"Zuo","year":"2021","journal-title":"Inflammation"},{"issue":"20","key":"2024080708090549500_ref28","doi-asserted-by":"crossref","first-page":"10401","DOI":"10.1039\/D2FO01490D","article-title":"Rutin prevents seizures in kainic acid-treated rats: evidence of glutamate levels, inflammation and neuronal loss modulation","volume":"13","author":"Chang","year":"2022","journal-title":"Food Funct"},{"key":"2024080708090549500_ref29","doi-asserted-by":"crossref","first-page":"100135","DOI":"10.1016\/j.prmcm.2022.100135","article-title":"Rutin protects against cyclophosphamide induced immunological stress by inhibiting TLR4-NF-\u03baB-mediated inflammation and activating the Nrf2-mediated antioxidant responses","volume":"4","author":"Lan","year":"2022","journal-title":"Pharmacol Res-Mod Chinese Med"},{"key":"2024080708090549500_ref30","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.cbi.2015.02.021","article-title":"Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NF\u03baB\/MAPK pathway","volume":"231","author":"Nafees","year":"2015","journal-title":"Chem Biol Interact"}],"container-title":["Toxicology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/13\/4\/tfae108\/58648826\/tfae108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxres\/article-pdf\/13\/4\/tfae108\/58648826\/tfae108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T18:12:42Z","timestamp":1723054362000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxres\/article\/doi\/10.1093\/toxres\/tfae108\/7720776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxres\/tfae108","relation":{},"ISSN":["2045-4538"],"issn-type":[{"value":"2045-4538","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,8]]},"published":{"date-parts":[[2024,7,1]]},"article-number":"tfae108"}}