PMID- 25239813 OWN - NLM STAT- MEDLINE DCOM- 20150825 LR - 20150129 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 23 IP - 1 DP - 2014 Nov TI - The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF-kappaB pathway activation. PG - 294-303 LID - S1567-5769(14)00346-4 [pii] LID - 10.1016/j.intimp.2014.09.005 [doi] AB - BACKGROUND: Baicalin holds a protective effect on inflammatory responses in several diseases. However, its molecular mechanism of anti-inflammatory activity on ulcerative colitis (UC) remains unknown. The present study was conducted to verify whether the anti-inflammation effect of baicalin on experimental colitis is via inhibiting TLR4/NF-kappaB pathway activation. METHODS: The inflammatory response in RAW264.7 cells was induced by LPS and in rats by intrarectal administration of TNBS. Western blot analysis was carried out to examine toll-like receptor 4 (TLR4), NF-kappaB, p-NF-kappaB p65, IkappaB and p-IkappaB protein expressions in cells. Furthermore, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox-2), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 levels in cell supernatant and rat serum were detected by appropriate kits. An immunohistochemical assay was applied to examine TNF-alpha and IL-1beta protein expression in colon tissues and TLR4 and p-NF-kappaB p65 protein expressions in RAW264.7 cells. RESULTS: Baicalin ameliorates the considered inflammatory symptoms of induced colitis. It could also down-regulate pro-inflammatory mediators in the colon mucosa. The decline in the production of pro-inflammatory cytokines was correlated with the decrease in mucosal TLR4 protein expression. The expression of p-NF-kappaB p65 protein was significantly decreased, which correlated with a similar decrease in p-IkappaB protein. Consistent with the in vivo results, baicalin blocked LPS-stimulated nuclear translocation of p-NF-kappaB p65 in mouse macrophage RAW264.7 cells. CONCLUSIONS: The present study indicates for the first time that the mechanism for baicalin on abrogating experimental colitis was targeted inhibition of the TLR4/NF-kappaB pathway activation. CI - Copyright (c) 2014. Published by Elsevier B.V. FAU - Cui, Li AU - Cui L AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. FAU - Feng, Liang AU - Feng L AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. FAU - Zhang, Zhen Hai AU - Zhang ZH AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. FAU - Jia, Xiao Bin AU - Jia XB AD - Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140918 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Flavonoids) RN - 0 (NF-kappa B) RN - 0 (Toll-Like Receptor 4) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 347Q89U4M5 (baicalin) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage MH - Cell Line MH - Chemokine CCL2/metabolism MH - Colitis, Ulcerative/*drug therapy/immunology MH - Colon/*drug effects/immunology MH - Cytokines/metabolism MH - Disease Models, Animal MH - Flavonoids/*administration & dosage MH - Humans MH - Intercellular Adhesion Molecule-1/metabolism MH - Male MH - Mice MH - NF-kappa B/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects MH - Toll-Like Receptor 4/*metabolism OTO - NOTNLM OT - Baicalin OT - NF-kappaB OT - Pathway OT - TLR4 OT - Ulcerative colitis EDAT- 2014/09/23 06:00 MHDA- 2015/08/26 06:00 CRDT- 2014/09/21 06:00 PHST- 2014/08/06 00:00 [received] PHST- 2014/08/19 00:00 [revised] PHST- 2014/09/05 00:00 [accepted] PHST- 2014/09/21 06:00 [entrez] PHST- 2014/09/23 06:00 [pubmed] PHST- 2015/08/26 06:00 [medline] AID - S1567-5769(14)00346-4 [pii] AID - 10.1016/j.intimp.2014.09.005 [doi] PST - ppublish SO - Int Immunopharmacol. 2014 Nov;23(1):294-303. doi: 10.1016/j.intimp.2014.09.005. Epub 2014 Sep 18.