Phytochemicals as Novel Therapeutic Strategies for NLRP3 Inflammasome-Related Neurological, Metabolic, and Inflammatory Diseases

Abstract

Several lines of evidence point out the relevance of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome as a pivotal player in the pathophysiology of several neurological and psychiatric diseases (i.e., Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and major depressive disorder), metabolic disorders (i.e., obesity and type 2 diabetes) and chronic inflammatory diseases (i.e., intestinal inflammation, arthritis, and gout). Intensive research efforts are being made to achieve an integrated view about the pathophysiological role of NLRP3 inflammasome pathways in such disorders. Evidence is also emerging that the pharmacological modulation of NLRP3 inflammasome by phytochemicals could represent a promising molecular target for the therapeutic management of neurological, psychiatric, metabolic, and inflammatory diseases. The present review article has been intended to provide an integrated and critical overview of the available clinical and experimental evidence about the role of NLRP3 inflammasome in the pathophysiology of neurological, psychiatric, metabolic, and inflammatory diseases, including PD, AD, MS, depression, obesity, type 2 diabetes, arthritis, and intestinal inflammation. Special attention has been paid to highlight and critically discuss current scientific evidence on the effects of phytochemicals on NLRP3 inflammasome pathways and their potential in counteracting central neuroinflammation, metabolic alterations, and immune/inflammatory responses in such diseases.

5‐Heptadecylresorcinol, a Biomarker for Whole Grain Rye Consumption, Ameliorates Cognitive Impairments and Neuroinflammation in APP/PS1 Transgenic Mice

“…[ 17 ] Evidence suggests that deficiency of NLRP3 and ASC could decrease Aβ plaque deposition and reduce microglial inflammatory activation both in vitro and in vivo. [ 20 ] Therefore, targeting the NLRP3 inflammasome associated neuroinflammation is an efficient way for neuroprotection. Many plant‐derived natural compounds including epigallocatechin gallate (EGCG), curcumin and resveratrol have been studied for exerting neuroprotective activity though regulating NLRP3 inflammasome‐mediated IL‐1β production.…”

The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

“…Nowadays, curcumin is widely used due to its multiple biological activities, encompassing anti-inflammatory, anti-oxidant, scavenging reactive oxidative species (ROS), regulation of mitochondrial homeostasis, stem cell modulation, and neurogenesis [ 4 ]. Hence, curcumin may be useful in a wide range of human diseases, encompassing cardiovascular [ 5 , 6 ], inflammatory [ 7 , 8 ], and metabolic disorders [ 9 , 10 , 11 ].…”

Associations Between the NLRP3 and IL-1β Gene Polymorphisms and Gout Susceptibility

“…and release to extracellular which cause in ammation [21][22][23] .There are many pathogenesis of gout,but some scholars believe that MSU crystals stimulus NLRP3 protein lead to the release of IL-1β have a crucial role in gout.And increasing evidence indicates that [24][25][26] NLPR3 participate the onset of gout,diabetes,rheumatoid arthritis,systemic lupus erythematosus,Sjogren's syndrome,atherosclerosis,autoin ammatory syndromes and so on.…”