Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice...

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Main Authors: Dacheng Wu, Keyan Wu, Qingtian Zhu, Weiming Xiao, Qing Shan, Zhigang Yan, Jian Wu, Bin Deng, Yan Xue, Weijuan Gong, Guotao Lu, Yanbing Ding
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/3048532
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author Dacheng Wu
Keyan Wu
Qingtian Zhu
Weiming Xiao
Qing Shan
Zhigang Yan
Jian Wu
Bin Deng
Yan Xue
Weijuan Gong
Guotao Lu
Yanbing Ding
author_facet Dacheng Wu
Keyan Wu
Qingtian Zhu
Weiming Xiao
Qing Shan
Zhigang Yan
Jian Wu
Bin Deng
Yan Xue
Weijuan Gong
Guotao Lu
Yanbing Ding
author_sort Dacheng Wu
collection DOAJ
description Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.
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spelling doaj-art-9979fbf3730346eea2c09f02bdd73ec72025-02-03T05:43:44ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/30485323048532Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling PathwayDacheng Wu0Keyan Wu1Qingtian Zhu2Weiming Xiao3Qing Shan4Zhigang Yan5Jian Wu6Bin Deng7Yan Xue8Weijuan Gong9Guotao Lu10Yanbing Ding11Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaLaboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaLaboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaFormononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.http://dx.doi.org/10.1155/2018/3048532
spellingShingle Dacheng Wu
Keyan Wu
Qingtian Zhu
Weiming Xiao
Qing Shan
Zhigang Yan
Jian Wu
Bin Deng
Yan Xue
Weijuan Gong
Guotao Lu
Yanbing Ding
Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway
Mediators of Inflammation
title Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway
title_full Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway
title_fullStr Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway
title_full_unstemmed Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway
title_short Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway
title_sort formononetin administration ameliorates dextran sulfate sodium induced acute colitis by inhibiting nlrp3 inflammasome signaling pathway
url http://dx.doi.org/10.1155/2018/3048532
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