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Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro

Authors Ge H, Tang H, Liang Y, Wu J, Yang Q, Zeng L, Ma Z

Received 23 January 2017

Accepted for publication 25 April 2017

Published 6 June 2017 Volume 2017:11 Pages 1663—1671

DOI https://doi.org/10.2147/DDDT.S133069

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Rasika Samarasinghe

Peer reviewer comments 2

Editor who approved publication: Professor Manfred Ogris

Hui Ge,1,* Hao Tang,2,* Yanbing Liang,2 Jingguo Wu,2 Qing Yang,2 Lijin Zeng,2 Zhongfu Ma2

1Department of Health Care Clinic, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 2Department of General Internal Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

*These authors contributed equally to this work

Abstract: Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein. In addition, the production of proinflammatory cytokines, including IL-6, IL-1β, and tumor necrosis factor-α, were significantly reduced in lipopolysaccharide (LPS)-induced RAW264.7 macrophages treated with rhein. Parallel to the inhibition of proinflammatory cytokines, rhein significantly reduced phosphorylation levels of NF-κB p65 and inducible nitric oxide synthase, as well as COX-2 protein expression levels. Furthermore, rhein significantly reduced NALP3 and cleaved IL-1β expression in LPS + ATP-induced RAW264.7 macrophages. Thus, the present study demonstrates that rhein may exhibit its anti-inflammatory action via inhibition of NF-κB and NALP3 inflammasome pathways.

Keywords: rhein, inflammatory, zebrafish, NF-κB, iNOS, COX-2, NALP3

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