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Ursolic Acid Isolated from the Seed of Cornus officinalis Ameliorates Colitis in Mice by Inhibiting the Binding of Lipopolysaccharide to Toll-like Receptor 4 on Macrophages.
MedLine Citation:
PMID:  25213465     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ursolic acid, which was isolated from an ethanol extract of Cornus officinalis fruit, potently inhibited NF-κB activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages. Therefore, we investigated anti-inflammatory mechanism of ursolic acid in LPS-stimulated macrophages and colitic mice. Ursolic acid inhibited phosphorylation of IRAK1, TAK1, IKKβ and IκBα, as well as activation of NF-κB and MAPKs in LPS-stimulated macrophages. Ursolic acid suppressed LPS-stimulated IL-1β, IL-6, TNF-α, COX-2 and iNOS expression, as well as PGE2 and NO levels. Ursolic acid not only inhibited the Alexa Fluor 488-conjugated LPS-mediated shift of macrophages, but also reduced the intensity of fluorescent LPS bound to the macrophages transiently transfected with or without MyD88 siRNA. However, ursolic acid did not suppress NF-κB activation in peptidoglycan-stimulated macrophages. Oral administration of ursolic acid significantly inhibited 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colon shortening and myeloperoxidase activity in mice. Ursolic acid also suppressed TNBS-induced COX-2 and iNOS expression, as well as NF-κB activation in colon tissues. Ursolic acid (20 mg/kg) also inhibited TNBS-induced IL-1β, IL-6, TNF-α, by 93 %, 86% and 85%, respectively (P < 0.05). However, ursolic acid reversed TNBS-mediated downregulation of IL-10 expression to 79% of the normal control group (P < 0.05). Based on these findings, ursolic acid may ameliorate colitis by regulating NF-κB and MAPK signaling pathways via the inhibition of LPS binding to TLR4 on immune cells.
Authors:
Se-Eun Jang; Jin-Ju Jeong; Supriya R Hyam; Myung Joo Han; Dong-Hyun Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-12
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  -     ISSN:  1520-5118     ISO Abbreviation:  J. Agric. Food Chem.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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