{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:56:41Z","timestamp":1790639801963,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006014","name":"College of Medicine and Health Sciences, United Arab Emirates University","doi-asserted-by":"publisher","award":["12M156"],"award-info":[{"award-number":["12M156"]}],"id":[{"id":"10.13039\/501100006014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Peroxisome proliferator\u2010activated receptors (PPARs), functioning as nuclear receptors, regulate the expression of genes associated with inflammation, lipid metabolism, and glucose metabolism. The primary isotypes of PPARs are <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/ObjectDisplayForward?objectId=593\">PPAR\u03b1<\/jats:ext-link>, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/ObjectDisplayForward?objectId=594\">PPAR\u03b2<\/jats:ext-link>, and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/objectdisplayforward\/?objectId=595\">PPAR\u03b3<\/jats:ext-link>. PPAR\u03b3 is mostly expressed in adipose tissue and the colon. The activation of PPAR\u03b3 modulates signaling pathways associated with metabolism and inflammation. Inflammatory bowel diseases (IBDs) include Crohn's disease and ulcerative colitis (UC). Ulcerative colitis is predominantly localized to the colon. Considering PPAR\u03b3's expression profile and its role in alleviating inflammation, there exists an opportunity to explore pharmaceutical targeting in the colon to diminish inflammation. We conducted molecular docking and dynamics investigations utilizing <jats:italic>Morin hydrate<\/jats:italic> (MH), a flavonoid derived from the <jats:italic>Moraceae<\/jats:italic> family, with the cocrystal structure of PPAR\u03b3 and Nrf2. They demonstrated a consistent interaction. Consequently, we conducted comprehensive preclinical studies of these interactions utilizing both in\u00a0vivo and in\u00a0vitro models of colon inflammation. Our findings showed that MH reduced the disease activity index, colon length shortening, and myeloperoxidase enzyme activity in mice treated with dextran sodium sulfate (DSS). MH also safeguarded colon histology by reducing proinflammatory cytokines. MH induced Nrf2 nuclear translocation, enhanced antioxidant response, and elevated Nrf2 promoter activity. MH selectively enhanced PPAR\u03b3 protein expression while leaving other PPAR isotypes unaffected. HT\u201029 cells, treated with tumor necrosis factor\u2010alpha (TNF\u03b1) as an in\u00a0vitro model of colon inflammation, exhibited a reduction in proinflammatory chemokines with exposure to MH. MH also enhanced PPAR\u03b3 promoter activity. These findings demonstrate that MH is a potent agonist of Nrf2 and PPAR\u03b3, resulting in reduced colon inflammation.<\/jats:p>","DOI":"10.1002\/prp2.70132","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T03:13:14Z","timestamp":1751598794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Docking, Dynamics, and Preclinical Studies Reveal Morin Hydrate as a Potent <scp>PPAR\u03b3<\/scp> and Nrf2 Agonist That Mitigates Colon Inflammation"],"prefix":"10.1002","volume":"13","author":[{"given":"Aya A.","family":"Touny","sequence":"first","affiliation":[{"name":"Department of Physiology College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"},{"name":"Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy Ahram Canadian University  6th of October Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeeda","family":"Almarzooqi","sequence":"additional","affiliation":[{"name":"Department of Pathology College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh B.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Sinhgad College of Pharmacy  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhoomendra A.","family":"Bhongade","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry RAK College of Pharmacy, RAK Medical &amp; Health Sciences University  Ras Al Khaimah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Harja\u010dek","sequence":"additional","affiliation":[{"name":"Head of Division of Rheumatology Children's Hospital Srebrnjak  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahir A.","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-2966","authenticated-orcid":false,"given":"Shreesh","family":"Ojha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamanth Neralagundi","family":"Harihar Gowdru","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"},{"name":"Zayed Bin Sultan Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-500X","authenticated-orcid":false,"given":"Sandeep B.","family":"Subramanya","sequence":"additional","affiliation":[{"name":"Department of Physiology College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"},{"name":"Zayed Bin Sultan Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020805"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.341"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.08.064"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00730"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1254317"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2009.01.009"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.673046"},{"issue":"24","key":"e_1_2_10_9_1","first-page":"8839","article-title":"PPAR\u2010\u03b3 With Its Anti\u2010Inflammatory and Anti\u2010Fibrotic Action Could Be an Effectivetherapeutic Target in IBD","volume":"22","author":"Vetuschi A.","year":"2018","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.51.1.289"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MIB.0000195385.19268.68"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2007.09.003"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.06.049"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.12.012"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20765"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21322"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.3397"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.11.001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae082"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v12.i10.1050"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082244"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i28.5097"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.798038"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i8.877"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8040211"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27092901"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867323666160106150821"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107234"},{"issue":"5","key":"e_1_2_10_29_1","first-page":"475","article-title":"Morin Hydrate Downregulates Inflammation\u2010Mediated Nitric Oxide Overproduction and Potentiates Antioxidant Mechanism Against Anticancer Drug Doxorubicin Oxidative Hepatorenal Toxicity in Rats","volume":"13","author":"Famurewa A. C.","year":"2023","journal-title":"Avicenna Journal of Phytomedicine"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/1721727X231199414"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05293-x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112846"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1158945"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-4655(95)00042-E"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct300400x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21367"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00344a001"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2408420"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.448118"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.328693"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.470043"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13041343"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23764"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-016-0477-5"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01089"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1525s104"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12506462"},{"issue":"2","key":"e_1_2_10_49_1","first-page":"238","article-title":"Clinicopathologic Study of Dextran Sulfate Sodium Experimental Murine Colitis","volume":"69","author":"Cooper H. S.","year":"1993","journal-title":"Laboratory Investigation"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12072032"},{"key":"e_1_2_10_52_1","first-page":"130","article-title":"A Modified Spectrophotometric Assay of Superoxide Dismutase","volume":"21","author":"Kakkar P.","year":"1984","journal-title":"Indian Journal of Biochemistry and Biophysics"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(72)90132-7"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00031.2009"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70196-9"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020236"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201800202"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.042465"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2023.10.002"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14060652"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242417538"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40200-022-01057-5"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2020.20.e32"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13060696"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10050743"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0219720008003618"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.624112"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4714914"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.02262.x"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.06.149"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70132","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T09:05:53Z","timestamp":1755075953000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.70132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":69,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/prp2.70132"],"URL":"https:\/\/doi.org\/10.1002\/prp2.70132","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,4]]},"assertion":[{"value":"2024-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70132"}}