Dataset Information

Colitis Is Effectively Ameliorated by (±)-8-Acetonyl-dihydrocoptisine via the XBP1-NF-?B Pathway.

ABSTRACT: Ulcerative colitis (UC) is a recurrent, chronic intestinal disease. Available treatments for UC are poor effective and/or cause severe adverse events. X-box binding protein 1 (XBP1) and nuclear factor-?B (NF-?B) have been reported to play important roles in UC. Specifically, deletion or downregulation of XBP1 leads to spontaneous enteritis and results in imbalanced secretion of NF-?B and other proinflammatory cytokines. (±)-8-acetonyl-dihydrocoptisine, i.e., (±)-8-ADC, is a monomer semi-synthesized from coptisine. In vitro, (±)-8-ADC activated the transcriptional activity of XBP1, inhibited expression of NF-?B, and reduced production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-?) and interleukin-1 beta (IL-1?), in lipopolysaccharide-stimulated IEC6 cells. Therefore, silencing XBP1 would reduce the inhibition effect of (±)-8-ADC on NF-?B expression and the cytokines secretion in vitro. In a dextran sulfate sodium-induced colitis mouse model, oral administration of (±)-8-ADC ameliorated weight loss and colon contracture, and decreased the average disease activity index score and pathological damage. Simultaneously, (±)-8-ADC also increased XBP1 expression, and decreased NF-?B expression and secretion of myeloperoxidase, TNF-?, IL-6 and IL-1? in the colon. Therefore, (±)-8-ADC may ameliorate UC via the XBP1-NF-?B pathway and should be considered as a therapeutic candidate for UC.

SUBMITTER: Zhang H

PROVIDER: S-EPMC5591823 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Colitis Is Effectively Ameliorated by (±)-8-Acetonyl-dihydrocoptisine via the XBP1-NF-κB Pathway.

Zhang HaiJing H Song GuangMing G Zhang ZhiHui Z Song HuaChen H Tang XiaoNan X Deng AnJun A Wang WenJie W Wu LianQiu L Qin HaiLin H

Frontiers in pharmacology 20170905

Ulcerative colitis (UC) is a recurrent, chronic intestinal disease. Available treatments for UC are poor effective and/or cause severe adverse events. X-box binding protein 1 (XBP1) and nuclear factor-κB (NF-κB) have been reported to play important roles in UC. Specifically, deletion or downregulation of XBP1 leads to spontaneous enteritis and results in imbalanced secretion of NF-κB and other proinflammatory cytokines. (±)-8-acetonyl-dihydrocoptisine, i.e., (±)-8-ADC, is a monomer semi-synthesi ...[more]

PMID: 28928666

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Dataset Information

Colitis Is Effectively Ameliorated by (±)-8-Acetonyl-dihydrocoptisine via the XBP1-NF-?B Pathway.

Publications

Colitis Is Effectively Ameliorated by (±)-8-Acetonyl-dihydrocoptisine via the XBP1-NF-κB Pathway.

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