Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses

• Published in: Molecular nutrition & food research 2018-07, Vol.62 (13), p.e1800147-n/a
• Main Author: Yi, Young‐Su
• Format: Article
• Language: English
• Subjects: Animals; anti‐inflammatory; Apigenin - pharmacology; Apoptosis; Biflavonoids - pharmacology; Caspase; Catechin - analogs & derivatives; Catechin - pharmacology; Cell activation; Cell death; Chalcones - pharmacology; Drug Development; Flavonoids; Flavonoids - pharmacology; Flavonoids - therapeutic use; Health promotion; Humans; Immune response; Immune system; Inflammasomes; Inflammasomes - chemistry; Inflammasomes - drug effects; Inflammasomes - physiology; Inflammation - drug therapy; Inflammatory diseases; Innate immunity; Interleukins; Luteolin - pharmacology; Melanoma; Metabolites; Molecular chains; Oligomerization; Pain perception; Pattern recognition; Pattern recognition receptors; Priming; Proanthocyanidins - pharmacology; Proteins; PRRs; Pyroptosis; Quercetin - pharmacology; Receptors; Rutin - pharmacology; Secondary metabolites; Suppressors
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201800147

Inflammation is an innate immune response to noxious stimuli to protect the body from pathogens. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory cells increase expressions of inflammatory molecules, while in triggering, inflammasomes are activated, resulting in cell death and pro‐inflammatory cytokine secretion. Inflammasomes are protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g., nucleotide‐binding oligomerization domain‐like receptors (NLRs), absent in melanoma 2 (AIM2), and caspases‐4/5/11) and pro‐caspase‐1 with or without a bipartite adaptor molecule ASC. Inflammasome activation induces pyroptosis, inflammatory cell death, and stimulates caspase‐1‐mediated secretion of interleukin (IL)‐1b and IL‐18. Flavonoids are secondary metabolites found in various plants and are considered as critical ingredients promoting health and ameliorating various disease symptoms. Anti‐inflammatory activity of flavonoids and underlying mechanisms have been widely studied. This review introduces current knowledge on different types of inflammasomes and their activation during inflammatory responses and discusses recent studies regarding anti‐inflammatory roles of flavonoids as suppressors of inflammasomes in inflammatory conditions. Understanding the regulatory effects of flavonoids on inflammasome activation will increase our knowledge of flavonoid‐mediated anti‐inflammatory activity and provide new insights into the development of flavonoid preparations to prevent and treat human inflammatory diseases. An up‐to‐date review on the anti‐inflammatory activity of flavonoids, including quercetin, luteolin, apigenin, epigallocatechin gallate (EGCG), rutin, isoliquiritigenin (ISL), and procyanidins, focusing on the inhibition of inflammasome activation in inflamed cells, is given. Flavonoids play a suppressive role on inflammatory responses and the pathogenesis of inflammatory diseases by inhibiting the activation of various types of inflammasomes, such as NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes in inflamed cells. The anti‐inflammatory property of flavonoids by inhibiting inflammasome activation, a critical mechanism to suppress inflammatory responses, and flavonoid‐mediated selective targeting of inflammasome components could be a promising strategy to prevent and treat inflammatory diseases.