Plant-derived bioactive compounds regulate the NLRP3 inflammasome to treat NAFLD

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by abnormal accumulation of hepatic fat and inflammatory response with complex pathogenesis. Over activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the secretion of interleukin (IL)-1β and IL-18, induces pyroptosis, and promotes the release of a large number of pro-inflammatory proteins. All of which contribute to the development of NAFLD. There is a great deal of evidence indicating that plant-derived active ingredients are effective and safe for NAFLD management. This review aims to summarize the research progress of 31 active plant-derived components (terpenoids, flavonoids, alkaloids, and phenols) that alleviate lipid deposition, inflammation, and pyroptosis by acting on the NLRP3 inflammasome studied in both in vitro and in vivo NAFLD models. These studies confirmed that the NLRP3 inflammasome and its related genes play a key role in NAFLD amelioration, providing a starting point for further study on the correlation of plant-derived compounds treatment with the NLRP3 inflammasome and NAFLD.

ATL I, Acts as a SIRT6 Activator to Alleviate Hepatic Steatosis in Mice via Suppression of NLRP3 Inflammasome Formation

“…Krüppel-like Factor 16 directly bonded the promoter of PPARα to increase FFA oxidation, reduce lipid deposition, and decrease the reactive oxygen species (ROS) level to ameliorate insulin resistance and steatohepatitis [17]. Toll-like receptor (TLR)/NF-κB signaling promoted the formation of the NLRP3 inflammasome, and then resulted in IL-1β maturation and caspase-1 activation to promote the initiation and progression of MAFLD [18,19]. Myeloidspecific NLRP3 ablation impaired the NLRP3 inflammasome to inhibit pro-inflammatory cytokine release [20].…”

“…Generally, hepatic steatosis management includes exercise, diet control, and drug intervention. Emerging natural compounds and their derivatives have exhibited promising therapeutic effects on conditions including, but not limited to, liver diseases [18,26,27]. Atractylenolide III activates the hepatic adiponectin receptor 1 (AdipoR1)/AMPK axis to ameliorate non-alcoholic fatty liver disease [28].…”