Regulatory Roles of Flavonoids on Inflammasome Activation during Inflammatory Responses

Abstract

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.

Protective effect of linoleic acid against inflammatory reactions by mast cell via caspase‐1 cascade pathways

“…In addition, caspase-1 inhibitor, VX-765 completely diminished the course of inflammatory reaction and hypersensitivity (Stack et al, 2005). Yi (2018) reported that flavonoids in functional foods have an anti-inflammatory activity by reducing caspase-1 activities.…”

“…In addition, caspase‐1 inhibitor, VX‐765 completely diminished the course of inflammatory reaction and hypersensitivity (Stack et al, ). Yi () reported that flavonoids in functional foods have an anti‐inflammatory activity by reducing caspase‐1 activities. Caspase‐1 is also an upstream molecule of NF‐κB, which is transcription factor of inflammatory mediators in human mast cells and caspase‐1 inhibitor reduces the expression of TSLP (an initiation factor of AD) by the inhibition of NF‐κB (Moon & Kim, ).…”

“…MAPKs accelerated a downstream inflammatory response (Han et al, 2014). Therefore, these molecules such as caspase-1, NF-κB, Many health functional foods and the active constituents contained in these foods have been revealed an anti-inflammatory activity (Yi, 2018). A large number of mechanistic researches have nicely verified that these functional foods have the anti-allergic inflammatory activities by reducing the levels of inflammatory mediators, such as TSLP, TNF, IL-1β, IL-6, and IL-8 and suppressing the inflammatory signaling pathways, such as caspase-1, NF-κB, and MAPKs Kim et al, 2017).…”

Ethnopharmacology of Fruit Plants: A Literature Review on the Toxicological, Phytochemical, Cultural Aspects, and a Mechanistic Approach to the Pharmacological Effects of Four Widely Used Species

“…The mechanism proposed for inhibiting activation by flavonoids was based on the regulation of the expression of inflammasome components such as the amino-terminal pyrin domain (PYD), which interacts with the ASC pyrin domain (caspase recruitment domain) to initiate the assembly of the inflammasome; the central nucleotide binding and oligomerization domain (NACHT), which has the ATPase activity necessary for NLRP3 oligomerization after activation; and C-terminal leucine-rich repeat (LRR) domain, whose function has not yet been identified. These changes can prevent its assembly and lead to inhibition of caspase-1 activation and, consequently, maturation and secretion of pro-inflammatory cytokines [ 41 , 42 ].…”

“…Thus, luteolin ( 6 ) is able to reduce the expression of interleukin-1 beta (IL-1β), a cytokine with a primary role in the inflammatory response, and interleukin-8 (IL-8), a chemokine that stimulates migration of immune cells. Another anti-inflammatory flavonoid found in T. esculenta seeds is rutin ( 10 ), which promotes the inhibition of the NLRP3 inflammasome activation through the negative regulation of the NLRP3, ASC and caspase-1 expression and reduced production of IL-1β and interleukin-18 (IL-18), which is also known as an interferon-γ inducing factor (IFN-γ) [ 41 , 48 ].…”