NLRP3 Inflammasome Formation and Activation in Nonalcoholic Steatohepatitis: Therapeutic Target for Antimetabolic Syndrome Remedy FTZ

Oxidative Medicine and Cellular Longevity
Yu ChenJiao Guo

Abstract

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), indi...Continue Reading

References

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Citations

Nov 25, 2020·Cellular and Molecular Life Sciences : CMLS·Inês Vieira da SilvaGraça Soveral
Apr 30, 2021·Frontiers in Pharmacology·Jianxiong WuQianfeng Gong
May 1, 2021·Clinics and Research in Hepatology and Gastroenterology·Yasar ColakTolga Erim
Aug 28, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mingtai ChenHua Zhou

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Methods Mentioned

BETA
density gradient centrifugation
confocal microscopy
X-ray
ELISA
ESR

Software Mentioned

MetaMorph
ImageJ
Image Pro Plus
Image
Pro Plus

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