Modulating NLRP3 Inflammasomes in Idiopathic Pulmonary Fibrosis: A Comprehensive Review on Flavonoid-Based Interventions

Abstract Idiopathic Pulmonary Fibrosis (IPF) is a severe, rapidly advancing disease that drastically diminishes life expectancy. Without treatment, it can progress to lung cancer. The precise etiology of IPF remains unknown, but inflammation and damage to the alveolar epithelium are widely thought to be pivotal in its development. Research has indicated that activating the NLRP3 inflammasome is a crucial mechanism in IPF pathogenesis, as it triggers the release of pro-inflammatory cytokines such as IL-1β, IL-18, and TGF-β. These cytokines contribute to the myofibroblast differentiation and extracellular matrix (ECM) accumulation. Currently, treatment options for IPF are limited. Only two FDA-approved medications, pirfenidone and nintedanib, are available. While these drugs can decelerate disease progression, they come with a range of side effects and do not cure the disease. Additional treatment strategies primarily involve supportive care and therapy. Emerging research has highlighted that numerous flavonoids derived from traditional medicines can inhibit the critical regulators responsible for activating the NLRP3 inflammasome. These flavonoids show promise as potential therapeutic agents for managing IPF, offering a new avenue for treatment that targets the core inflammatory processes of this debilitating condition. Graphical Abstract