Dietary polyphenols targeting NLRP3 inflammasome in obesity and metabolic disorders: a review on experimental and computational evidence

Obesity and its associated metabolic disorders, including type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular complications, represent a major global health burden. A key pathogenic mechanism linking these conditions is the overactivation of the NLRP3 inflammasome, which triggers caspase-1 activation and promotes proinflammatory cytokine release (e.g., IL-1β and IL-18), driving adipose tissue dysfunction, insulin resistance, and systemic inflammation. Emerging evidence highlights dietary polyphenols as natural modulators of NLRP3 activity attenuating inflammasome activation by regulating NF-κB signalling, reducing oxidative stress and restoring autophagy. Complementary in silico approaches (e.g., molecular docking, molecular dynamics simulations, network pharmacology) provide mechanistic insights into polyphenol-inflammasome interactions. This review summarises current evidence on the NLRP3’s role in obesity-related disorders and discusses the therapeutic potential of dietary polyphenols, underscoring directions for translational and multidisciplinary research.