Cyanidin-3-O-β-glucoside inactivates NLRP3 inflammasome and alleviates alcoholic steatohepatitis via SirT1/NF-κB signaling pathway.

Abstract

Alcoholic liver disease (ALD) is a major cause of liver disease worldwide. In patients with ALD, an increased level of hepatic inflammasome components was observed, together with an increased circulating pro-inflammatory cytokines. Cyanidin-3-O-β-glucoside (Cy-3-G) is a bioactive compound belonging to the anthocyanin group, which widely exists in deep-colored fruits and vegetables. Consumption of Cy-3-G is associated with lower risks of non-alcoholic fatty liver disease (NAFLD), liver fibrosis, obesity, atherosclerosis, and inflammation. However, whether Cy-3-G has effects on inflammasome formation and activation thereby protects against alcohol-induced liver damage remain elusive. In this study, we identified that dietary provision of Cy-3-G remarkably attenuated liver damage caused by excess energy intake and alcohol consumption. Supplement with Cy-3-G mediated NAD+ homeostasis, which stimulated SirT1 activity, resulting in suppressed NF-κB acetylation. Interestingly, Cy-3-G treatment suppressed NF-κB acetylation when SirT1 action was blunted by selective antagonist, and subsequently suppressed NLRP3 inflammasome activation and proinflammatory cytokines release in hepatic cell lines. Our findings first demonstrate that Cy-3-G at a physiologically achievable dosage alleviates alcohol-induced hepatic inflammation via inactivation of NLRP3 inflammasome and deacetylation of NF-κB, suggesting a promising therapeutic approach to alleviate alcohol-induced liver damage.

• Authors: Yujia Zhou, Sufan Wang, Ting Wan, Yuanling Huang, Nengzhi Pang, Xuye Jiang, Yingying Gu, Zhenfeng Zhang, Jing Luo, Lili Yang
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 160 Pg. 334-341 (11 20 2020) ISSN: 1873-4596 [Electronic] United States
• PMID: 32805401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Anthocyanins
• Inflammasomes
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• cyanidin-3-O-beta-glucopyranoside
• SIRT1 protein, human
• Sirtuin 1

Topics

• Anthocyanins (pharmacology)
• Fatty Liver, Alcoholic (drug therapy)
• Humans
• Inflammasomes
• NF-kappa B (genetics, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics)
• Signal Transduction
• Sirtuin 1 (genetics)