Sa450 SODIUM FERULATE AMELIORATES ACETIC ACID-INDUCED ACUTE COLITIS VIA INHIBITING NLRP3 INFLAMMASOME AND NF-κB ACTIVATION IN MICE

Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome is closely associated with intestinal inflammation because of its ability to increase IL-1β secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sodium sulfate (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index, shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1β secretion and NLRP3 inflammasome activation in colon samples and RAW 264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the Toll-like receptor 4/NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC. NEW & NOTEWORTHY Here, we identify a new role for growth differentiation factor 11 (GDF11), which ameliorates dextran sodium sulfate-induced acute colitis. Meanwhile, we discover a new phenomenon of GDF11 inhibiting IL-1β secretion and Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome activation. These findings reveal that GDF11 is a new potential candidate for the treatment of ulcerative colitis patients with a hyperactive NLRP3 inflammasome.

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

Mediators of Inflammation ◽

10.1155/2018/9878120 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3

Author(s):

Dacheng Wu ◽

Keyan Wu ◽

Qingtian Zhu ◽

Weiming Xiao ◽

Qing Shan ◽

...

Keyword(s):

Signaling Pathway ◽

Nlrp3 Inflammasome ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Acute Colitis

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Using Network Pharmacology for Systematic Understanding of Geniposide in Ameliorating Inflammatory Responses in Colitis Through Suppression of NLRP3 Inflammasome in Macrophage by AMPK/Sirt1 Dependent Signaling

The American Journal of Chinese Medicine ◽

10.1142/s0192415x20500846 ◽

2020 ◽

Vol 48 (07) ◽

pp. 1693-1713

Author(s):

Zhichen Pu ◽

Yanhao Liu ◽

Chao Li ◽

Moadi Xu ◽

Haitang Xie ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammatory Responses ◽

Receptor Protein ◽

Network Pharmacology ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Models ◽

Acute Colitis ◽

Raw264.7 Cell ◽

Anti Inflammatory ◽

Systematic Understanding

Ulcerative colitis is a chronic and recurrent inflammatory bowel disease mediated by immune response. Geniposide is the main active ingredient extracted from Gardenia jasminoides, which has been suggested to exert excellent efficacy on inflammatory disease. Herein, in this study, we aimed to uncover the systematic understanding of the mechanism and effects of geniposide in ameliorating inflammatory responses in colitis. In brief, the TCMSP server and GEO DataSets were used to analyze the systematic understanding of the mechanism and effects of geniposide in ameliorating inflammatory responses in colitis. Dextran Sulfate Sodium (DSS)-induced acute colitis of mice were administered with 25–100[Formula: see text]mg/kg of geniposide for 7 days by gavage. Lipopolysaccharide (LPS)-induced Bone Marrow Derived Macrophage (BMDM) cell or RAW264.7 cell models were treated with 20, 50 and 100[Formula: see text][Formula: see text]M of geniposide for 4[Formula: see text]h. Myeloperoxidase (MPO) activity and Interleukin-1[Formula: see text] (IL-1[Formula: see text] levels were measured using MPO activity kits and IL-1[Formula: see text] levels enzyme-linked immunosorbent assay (ELISA) kits, respectively. Additionally, Western blot was used to determine the relevant protein expression. As a result, Geniposide could ameliorate inflammatory responses and prevent colitis in DSS-induced acute colitis of mice by activating AMP-activated protein kinase (AMPK)/Transcription 1 (Sirt1) dependent signaling via the suppression of nod-like receptor protein 3 (NLRP3) inflammasome. Geniposide attenuated macrophage differentiation in DSS-induced acute colitis of mice. Geniposide suppressed NLRP3 inflammasome and induced AMPK/Sirt1 signaling in LPS-induced BMDM cell or RAW264.7 cell models. In mechanism studies, the inhibition of AMPK/Sirt1 attenuated the anti-inflammatory effects of geniposide in colitis. The activation of NLRP3 attenuated the anti-inflammatory effects of geniposide in colitis. Taken together, our results demonstrated that geniposide ameliorated inflammatory responses in colitis vai the suppression of NLRP3 inflammasome in macrophages by AMPK/Sirt1-dependent signaling.

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Topical anticolitic efficacy and selectivity of the glucocorticoid budesonide in a new model of acetic acid-induced acute colitis in the rat

Alimentary Pharmacology & Therapeutics ◽

10.1111/j.1365-2036.1994.tb00311.x ◽

2007 ◽

Vol 8 (4) ◽

pp. 433-446 ◽

Cited By ~ 12

Author(s):

R. FABIA ◽

A. ArRAJAB ◽

R. WILLÉN ◽

R. BRATTSAND ◽

M. ERLANSSON ◽

...

Keyword(s):

Acetic Acid ◽

Acute Colitis ◽

New Model

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

Mediators of Inflammation ◽

10.1155/2018/3048532 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 12

Author(s):

Dacheng Wu ◽

Keyan Wu ◽

Qingtian Zhu ◽

Weiming Xiao ◽

Qing Shan ◽

...

Keyword(s):

Tight Junction ◽

Nlrp3 Inflammasome ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Acute Injury ◽

Dependent Manner ◽

Protective Effects ◽

Tight Junction Proteins ◽

Acute Colitis ◽

Junction Proteins

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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