{"doi":"10.17615/0h91-pk81","title":"The Flavonoid Luteolin Worsens Chemical-Induced Colitis in NF-κBEGFP Transgenic Mice through Blockade of NF-κB-Dependent Protective Molecules","abstract":"BackgroundThe flavonoid luteolin has anti-inflammatory properties both in vivo and in vitro. However, the impact of luteolin on experimental models of colitis is unknown.Methodology/Principal FindingsTo address the therapeutic impact of luteolin, NF-κBEGFP transgenic mice were fed a chow diet containing 2% luteolin- or isoflavone-free control chow (AIN-76), and acute colitis was induced using 3% dextran sodium sulfate (DSS). Additionally, development of spontaneous colitis was evaluated in IL-10−/−;NF-κBEGFP transgenic mice fed 2% luteolin chow diet or control chow diet. Interestingly, NF-κBEGFP transgenic mice exposed to luteolin showed worse DSS-induced colitis (weight loss, histological scores) compared to control-fed mice, whereas spontaneous colitis in IL-10−/−;NF-κBEGFP mice was significantly attenuated. Macroscopic imaging of live resected colon showed enhanced EGFP expression (NF-κB activity) in luteolin-fed mice as compared to control-fed animals after DSS exposure, while cecal EGFP expression was attenuated in luteolin-fed IL-10−/− mice. Interestingly, confocal microscopy showed that EGFP positive cells were mostly located in the lamina propria and not in the epithelium. Caspase 3 activation was significantly enhanced whereas COX-2 gene expression was reduced in luteolin-fed, DSS-exposed NF-κBEGFP transgenic mice as assessed by Western blot and immunohistochemical analysis. In vitro, luteolin sensitized colonic epithelial HT29 cells to TNFα-induced apoptosis, caspase 3 activation, DNA fragmentation and reduced TNFα-induced C-IAP1, C-IAP2 and COX-2 gene expression.Conclusions/SignificanceWe conclude that while luteolin shows beneficial effects on spontaneous colitis, it aggravates DSS-induced experimental colitis by blocking NF-κB-dependent protective molecules in enterocytes.","journal":"UNC Libraries","year":2020,"id":140192,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":237266,"name":"Christian Jobin","orcid":"0000-0002-3733-1001","position":1,"is_corresponding":false},{"id":604486,"name":"Joo‐Sung Kim","orcid":"0000-0002-8173-9805","position":2,"is_corresponding":false},{"id":604487,"name":"Byung Ik Jang","orcid":"0000-0002-3037-9272","position":3,"is_corresponding":false},{"id":604485,"name":"Thomas Karrasch","orcid":"0000-0001-6850-588X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:17.077903Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}