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NLRP3 Inflammasome Formation and Activation in Nonalcoholic Steatohepatitis: Therapeutic Target for Antimetabolic Syndrome Remedy FTZ
Joint Authors
Guo, Jiao
Hong, Jinni
Chen, Yu
He, Xingxiang
Yuan, Xinxu
Bhat, Owais
Li, Guangbi
Li, Pin-Lan
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-07-22
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
The Nod-like receptor protein 3 (NLRP3) inflammasome activation not only serves as an intracellular machinery triggering inflammation but also produces uncanonical effects beyond inflammation such as changing cell metabolism and increasing cell membrane permeability.
The present study was designed to test whether this NLRP3 inflammasome activation contributes to the “two-hit” injury during nonalcoholic steatohepatitis (NASH) and whether it can be a therapeutic target for the action of Fufang Zhenzhu Tiaozhi (FTZ), a widely used herbal remedy for hyperlipidemia and metabolic syndrome in China.
We first demonstrated that NLRP3 inflammasome formation and activation as well as lipid deposition occurred in the liver of mice on the high-fat diet (HFD), as shown by increased NLRP3 aggregation, enhanced production of IL-1β and high mobility group box 1 (HMGB1), and remarkable lipid deposition in liver cells.
FTZ extracts not only significantly reduced the NLRP3 inflammasome formation and activation but also attenuated the liver steatosis and fibrogenic phenotype changed.
In in vitro studies, palmitic acid (PA) was found to increase colocalization of NLRP3 components and enhanced caspase-1 activity in hepatic stellate cells (HSCs), indicating enhanced formation and activation of NLRP3 inflammasomes by PA.
PA also increased lipid deposition.
Nlrp3 siRNA can reverse this effect by silencing the NLRP3 inflammasome and both with FTZ.
In FTZ-treated cells, not only inflammasome formation and activation was substantially attenuated but also lipid deposition in HSCs was blocked.
This inhibition of FTZ on lipid deposition was similar to the effects of glycyrrhizin, an HMGB1 inhibitor.
Mechanistically, stimulated membrane raft redox signaling platform formation and increased O2•− production by PA to activate NLRP3 inflammasomes in HSCs was blocked by FTZ treatment.
It is concluded that FTZ extracts inhibit NASH by its action on both inflammatory response and liver lipid metabolism associated with NLRP3 inflammasome formation and activation.
American Psychological Association (APA)
Chen, Yu& He, Xingxiang& Yuan, Xinxu& Hong, Jinni& Bhat, Owais& Li, Guangbi…[et al.]. 2018. NLRP3 Inflammasome Formation and Activation in Nonalcoholic Steatohepatitis: Therapeutic Target for Antimetabolic Syndrome Remedy FTZ. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1211125
Modern Language Association (MLA)
Chen, Yu…[et al.]. NLRP3 Inflammasome Formation and Activation in Nonalcoholic Steatohepatitis: Therapeutic Target for Antimetabolic Syndrome Remedy FTZ. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-13.
https://search.emarefa.net/detail/BIM-1211125
American Medical Association (AMA)
Chen, Yu& He, Xingxiang& Yuan, Xinxu& Hong, Jinni& Bhat, Owais& Li, Guangbi…[et al.]. NLRP3 Inflammasome Formation and Activation in Nonalcoholic Steatohepatitis: Therapeutic Target for Antimetabolic Syndrome Remedy FTZ. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-13.
https://search.emarefa.net/detail/BIM-1211125
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211125