{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:06:18Z","timestamp":1793210778593,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP2025R119"],"award-info":[{"award-number":["RSP2025R119"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Rhamnetin is a naturally occurring flavonoid compound found in many wild plant species and indigenous fruits. Despite its numerous biological potentials, such as anti\u2010inflammatory, antioxidant and antimicrobial effects, there is a lack of literature elucidating its gastroprotective action and anticipating molecular mechanism. Natural products can be a good alternative to overcome the side effects and relapses associated with anti\u2010ulcer drugs. This study aims to elucidate rhamnetin's acute toxicity and gastroprotective effects using the indomethacin ulceration model. Animals were arbitrarily divided into five groups: a negative control group (A) and a positive control group (B), both treated with 1% carboxymethyl cellulose; a reference group (C) receiving 20\u2009mg\/kg omeprazole; and low\u2010dose (D) and high\u2010dose (E) rhamnetin groups receiving 30 and 60\u2009mg\/kg, respectively. After 1\u2009h, rats in Groups B\u2013E were subjected to indomethacin\u2010induced ulceration. Toxicity evaluations indicated the safety of rhamnetin at doses of up to 400\u2009mg\/kg in rats, without any noticeable physiological alterations. Rhamnetin (30 and 60\u2009mg\/kg) administered orally 1\u2009h before indomethacin\u2010induced gastric ulcer ameliorated the stomach lesions and lowered the ulcer index area by 73.81% and 77.87%, respectively. Rhamnetin supplementation ameliorated histopathological alterations and restored gastric barriers, including gastric pH and mucin secretion. Moreover, rhamnetin\u2010treated rats exhibited increased anti\u2010apoptotic heat shock protein 70 and decreased Bax protein in stomach tissues. These findings were in line with lowered accumulated MDA, increased superoxide dismutase, catalase and prostaglandin E2 levels, reduced serum inflammatory mediators (TNF\u2010\u03b1 and interleukin\u20106) and elevated interleukin\u201010 cytokines. The outcomes indicate rhamnetin's cicatrising and gastroprotective effects against indomethacin\u2010mediated ulceration, possibly due to its modulatory actions on oxidative stress, inflammation and apoptotic pathways.<\/jats:p>","DOI":"10.1111\/1440-1681.70029","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T01:48:56Z","timestamp":1740016136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Prophylactic Effects of Rhamnetin Flavonoid on Indomethacin\u2010Induced Gastric Ulceration by Modulating <scp>HSP<\/scp> 70\/Bax, <scp>SOD<\/scp>\/<scp>MDA<\/scp> and <scp>TNF<\/scp>\u2010\u03b1\/<scp>IL<\/scp>\u201010"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2451-0833","authenticated-orcid":false,"given":"Mohammed T.","family":"Mohammed","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Veterinary Medicine University of Kufa  Kufa Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talal Salem","family":"Al\u2010Qaisi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, Faculty of Allied Medical Sciences Al\u2010Ahliyya Amman University  Amman Jordan"},{"name":"Department of Biomedical Sciences, College of Health Sciences Abu Dhabi University  Abu Dhabi UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-4018","authenticated-orcid":false,"given":"Ahmed A. J.","family":"Jabbar","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Erbil Technical Health and Medical College Erbil Polytechnic University  Erbil Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M. H. M.","family":"Raouf","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Science Cihan University\u2010Erbil  Erbil Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parween AbdulSamad","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Education Salahaddin University  Erbil Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi A.","family":"Mothana","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer I.","family":"Fantoukh","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawaz Rizgar","family":"hassan","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, College of Science Knowledge University  Erbil Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmood Ameen","family":"Abdulla","sequence":"additional","affiliation":[{"name":"Department of Medical Analysis, Faculty of Applied Science Tishk International University  Erbil Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musher Ismael","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science and Health Koya University  Erbil Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Awad","sequence":"additional","affiliation":[{"name":"Research Associate, Department of Chemical Engineering Toronto Metropolitan University  Toronto Canada"},{"name":"Assistant Professor, School of Engineering Samarkand International University of Technology  Samarkand Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876\u2010022\u201002130\u20102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyac033"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13017\u2010019\u20100283\u20109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11130-025-01298-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.18647"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2017.0306"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2023.120822"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112958"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202114985"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116545"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102022\u2010004938"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2023.2297234"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000514975"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgac098"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2169551"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e20406"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114374"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061578"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4103\/2141-9248.126604"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgab163"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0FO02270E"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232112895"},{"key":"e_1_2_9_24_1","unstructured":"Guideline O \u201cAcute Oral Toxicity\u2010Acute Toxic Class Method. OECD Guidelines for the Testing of Chemicals \u201d(2001) 423."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917\u2010020\u201002451\u2010y"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11071230"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10111836"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.14712\/23362936.2019.5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-024-10211-7"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020584"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-024-10304-3"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06948-z"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10040595"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2691577"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/srt.13896"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115603"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/srt.13727"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2024.102459"},{"key":"e_1_2_9_39_1","first-page":"673","article-title":"Evaluation of the Effectiveness of Angiotensin\u2010Converting Enzyme Inhibitors, Misoprostol, Omeprazole and Their Combinations on the State of the Gastric Mucous Barrier in Indomethacin Gastropathy in Animals With Experimental Rheumatoid Arthritis","volume":"13","author":"Yakubov A. V.","year":"2022","journal-title":"Journal of Pharmaceutical Negative Results"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43450-024-00567-y"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.2478\/asn-2023-0012"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13596\u2010022\u201000674\u2010y"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43450\u2010023\u201000485\u20105"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/10520295.2021.2014569"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122417"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.29169\/1927-5951.2022.12.09"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2022.2156530"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.15586\/ijfs.v36i4.2723"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1134\/S106235902360085X"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.21123\/bsj.2024.10952"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.36472\/msd.v7i5.380"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.4162\/nrp.2015.9.6.586"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010022\u201004619\u20106"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2015.50831"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.70029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T09:20:07Z","timestamp":1741771207000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.70029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/1440-1681.70029"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.70029","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"assertion":[{"value":"2024-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70029"}}