Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome
Metrics: PDF 1529 views | HTML 2345 views | ?
Wei Zhou1, Xiuting Liu1, Xin Zhang1, Jingjing Tang1, Zhiyu Li2, Qing Wang3 and Rong Hu1
1State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China
2Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China
3Department of Neurosurgery, Wuxi Second Hospital Affiliated Nanjing Medical University, Wuxi 214002, China
Rong Hu, email: email@example.com
Qing Wang, email: firstname.lastname@example.org
Keywords: NLRP3 inflammasome, inflammatory bowel disease, oroxylin A, NF-κB, DSS-induced colitis
Received: March 29, 2017 Accepted: July 12, 2017 Published: July 22, 2017
NLRP3 inflammasome is a novel therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to investigate the anti-inflammatory effect of a bioactive flavonoid—oroxylin A on the treatment of dextran sulfate sodium (DSS)-induced murine colitis via targeting NLRP3 inflammasome. In this study, we found that oroxylin A attenuated experimental colitis in mice, including loss of body weights, shortening of the colon lengths and infiltration of inflammatory cells. The production of IL-1β, IL-6 and TNF-α in colon was also markedly reduced by oroxylin A. Moreover, oroxylin A significantly decreased the expression of NLRP3 in intestinal mucosal tissue. In addition, NLRP3-/- mice were observably protected from DSS-induced acute colitis, and oroxylin A treatment had no effects on attenuating inflammation in NLRP3-/- mice. Further study found that the activation of NLRP3 inflammasome was dose-dependently inhibited by oroxylin A in both THP-Ms and BMDMs, followed by decrease in the cleavage of caspase-1 and secretion of IL-1β. This inhibitory effect of oroxylin A was due to restraint of the NLRP3 protein expression and the inflammasome formation in macrophages. Furthermore, the reduction of NLRP3 protein expression by oroxylin A was dependent on the inhibition of NF-κB p65 expression and nuclear translocation. Besides, oroxylin A directly suppressed the ASC speck formation and the inflammasome assembly which in turn restrained the activation of NLRP3 inflammasome. Our findings demonstrated that oroxylin A inhibited NLRP3 inflammasome activation and could potentially be used for the treatment of IBD.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.