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Abstract Title:

Berberine Inhibits Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation and Pyroptosis in Nonalcoholic Steatohepatitisthe ROS/TXNIP Axis.

Abstract Source:

Front Pharmacol. 2020 ;11:185. Epub 2020 Mar 3. PMID: 32194416

Abstract Author(s):

Weijian Mai, Yangzhi Xu, Jiahui Xu, Dan Zhao, Liangying Ye, Ganxiang Yu, Zhilei Wang, Qianting Lu, Jiaen Lin, Tao Yang, Chengxin Gu, Shiming Liu, Yun Zhong, Hui Yang

Article Affiliation:

Weijian Mai

Abstract:

Berberine (BBR), an isoquinoline alkaloid originating from herbal plants, has been deemed beneficial for non-alcoholic fatty liver disease. Increasing evidence has demonstrated that Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the subsequent pyroptosis contribute to the progression of non-alcoholic steatohepatitis (NASH). However, whether BBR impacts NLRP3 inflammasome activation and pyroptosis in NASH and the potential mechanism remains unclear. In the current study, we found that BBR significantly decreased lipid accumulation, ameliorated reactive oxygen species (ROS) and lipid peroxides, Tumor necrosis factor alpha (TNF-α) expression, and phosphorylation of Nuclear factor kappa B (NF-κB) p65 bothandIn particular, BBR significantly inhibited NLRP3 expression, caspase-1 activity, and the pyroptosis executor, GSDMD-N, expression. In addition, BBR displayed similar inhibitory effects on NLRP3 inflammasome and pyroptosis with a decrease in ROS levels and TXNIP expression as N-acetyl-cysteine, a ROS scavenger, did. Whereas, the inhibitory effect of BBR on ROS, TXNIP expression, NLRP3 inflammasome activation and pyroptosis could be reversed by HOin AML12 cells. This study demonstrates that BBR's inhibitory effect on NLRP3 inflammasome activation and pyroptosis may be mediated by ROS/TXNIP axisfor the first time. Our findings suggest BBR is a potential candidate for the treatment of NASH.

Study Type : Animal Study

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