Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.

Xuexiu He,Zhengtao Yang,Jingjing Wang,Zhengkai Wei,Weijian Liu,Yunhe Fu,Jinhua Kou

doi:10.1038/srep28370

Xuexiu He, Zhengtao Yang + Show 5 more

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https://doi.org/10.1038/srep28370

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Journal: Scientific Reports	Publication Date: Jun 20, 2016
Citations: 134	License type: CC BY 4.0

Affiliation: Jilin Medical University, Jilin University

Abstract

Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment.

Highlights

Inflammatory bowel disease (IBD) is a noninfectious, chronic and relapsing inflammation of the gastrointestinal characterized by recurrent and long-lasting episodes of diarrhea and abdominal pain, which primarily manifests as ulcerative colitis (UC) and Crohn’s disease (CD)[1]
Our results demonstrated that the levels of pro-inflammatory cytokines TNF-αand IL-1βwere significantly increased after dextran sulfate sodium (DSS) administration, whereas administration of alpinetin significantly reduced the levels of these pro-inflammatory cytokines in a dose-dependent manner (Fig. 5)
We used the model of DSS-induced colitis mouse, the widely used model, to investigate the pathogenesis of inflammatory bowel disease (IBD) and the anti-inflammatory effect and mechanism of alpinetin via the inhibition of macrophage-mediated inflammation

Summary

Introduction

Inflammatory bowel disease (IBD) is a noninfectious, chronic and relapsing inflammation of the gastrointestinal characterized by recurrent and long-lasting episodes of diarrhea and abdominal pain, which primarily manifests as ulcerative colitis (UC) and Crohn’s disease (CD)[1]. The process of these two diseases consisted of a number of reactions, such as enetic, environmental, and immunological factors. There is little information about the effect of alpinetin on DSS-induced colitis in mice. This research aims to investigate the anti-inflammatory effect and mechanism of alpinetin in DSS-induced colitis in mice

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