Polyphenols, flavonoids and inflammasomes: the role of cigarette smoke in COPD

Abstract

COPD is predicted to become the third leading cause of morbidity and mortality worldwide by 2030. Cigarette smoking (active or passive) is one of its chief causes, with about 20% of cigarette smokers developing COPD from cigarette smoke (CS)-induced irreversible damage and sustained inflammation of the airway epithelium. Inflammasome activation leads to the cleavage of pro-interleukin (IL)-1β and pro-IL-18, along with the release of pro-inflammatory cytokines via gasdermin D N-terminal fragment membrane pores, which further triggers acute phase pro-inflammatory responses and concurrent pyroptosis. There is currently intense interest in the role of nucleotide-binding oligomerisation domain-like receptor family, pyrin domain containing protein-3 inflammasomes in chronic inflammatory lung diseases such as COPD and their potential for therapeutic targeting. Phytochemicals including polyphenols and flavonoids have phyto-medicinal benefits in CS-COPD. Here, we review published articles from the last decade regarding the known associations between inflammasome-mediated responses and ameliorations in pre-clinical manifestations of CS-COPD via polyphenol and flavonoid treatment, with a focus on the underlying mechanistic insights. This article will potentially assist the development of drugs for the prevention and therapy of COPD, particularly in cigarette smokers.

FIGURE 1

The relationships between current investigations of the signal pathways or targets of inflammasomes involved in COPD. ASC: apoptosis-associated speck-like protein containing a caspase recruitment domain; CS: cigarette smoke; CSE: cigarette smoke extract; DEP: diesel exhaust particle; eATP: extracellular ATP; eHSP70: extracellular heat shock protein 70kDa; GSDMD: gasdermin D; IL: interleukin; LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; NALP: NACHT, LRR and PYD domains-containing protein; NF-κB: nuclear factor-κB; NLRP3: nucleotide-binding oligomerisation domain-like receptor family, pyrin domain containing protein-3; TLR: Toll-like receptor; UFP: ultrafine particulate.

FIGURE 2

The acting target molecules of polyphenols and flavonoids on the signal pathways of cigarette smoke (CS)-induced inflammasome. Black boxes represent effects of CS/cigarette smoke extract (CSE), caused by the involvement of signal pathways. Red boxes contain the attenuating mediators of regulating signals. Green boxes display the acting targets of polyphenols and flavonoids. Black arrows depict stimulation whereas red “T” bars represent suppression. EC: endothelial cell; EGCG: epigallocatechin-3-gallate; ERK: extracellular signal-regulated kinases; GSDMD: gasdermin D; HO-1: haem oxygenase-1; HSYA: hydroxysafflor yellow A; IL: interleukin; ILG: isoliquiritigenin; ISOF: isoforskolin; LA: liquiritin apioside; MAPK: mitogen-activated protein kinase; MgIG: magnesium isoglycyrrhizinate; NF-κB: nuclear factor-κB; NLRP3: nucleotide-binding oligomerisation domain-like receptor family, pyrin domain containing protein-3; Nrf2: nuclear factor erythroid 2-related factor 2; ROS: reactive oxygen species; SIRT1: sirtuin 1.