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
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- 作者：Se-Eun Jang ; Jin-Ju Jeong ; Supriya R. Hyam ; Myung Joo Han ; Dong-Hyun Kim
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2014
- 出版时间：October 8, 2014
- 年：2014
- 卷：62
- 期：40
- 页码：9711-9721
- 全文大小：602K
- ISSN：1520-5118
文摘
Ursolic acid, which was isolated from an ethanol extract of Cornus officinalis seed, potently inhibited nuclear factor 魏 light-chain enhancer of activated B cells (NF-魏B) activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages. Therefore, we investigated the anti-inflammatory mechanism of ursolic acid in LPS-stimulated macrophages and colitic mice. Ursolic acid inhibited phosphorylation of interleukin 1 receptor-associated kinase (IRAK)1, TAK1, inhibitor of nuclear factor 魏B kinase subunit 尾 (IKK尾), and I魏B伪 as well as activation of NF-魏B and MAPKs in LPS-stimulated macrophages. Ursolic acid suppressed LPS-stimulated interleukin (IL)-1尾, IL-6, tumor necrosis factor (TNF)-伪, cyclooxygenase (COX)-2, and inducible NO synthetase (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-魏B activation in peptidoglycan-stimulated macrophages. Oral administration of ursolic acid significantly inhibited 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colon shortening and myeloperoxidase (MPO) activity in mice. Ursolic acid also suppressed TNBS-induced COX-2 and iNOS expression as well as NF-魏B activation in colon tissues. Ursolic acid (20 mg/kg) also inhibited TNBS-induced IL-1尾, IL-6, TNF-伪 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). On the basis of these findings, ursolic acid may ameliorate colitis by regulating NF-魏B and MAPK signaling pathways via the inhibition of LPS binding to TLR4 on immune cells.