Targeting NLRP3 inflammasome with curcumin: mechanisms and therapeutic promise in chronic inflammation.

Abstract

The NOD‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key molecular complex that amplifies inflammatory cascades by maturing interleukin‑1 beta (IL-1β) and interleukin‑18 (IL-18) and inducing pyroptosis. It serves as a major driver and co-driver of numerous diseases associated with chronic inflammation. Dysregulated NLRP3 activation contributes to the progression of disorders such as rheumatoid arthritis, inflammatory bowel disease, neurodegenerative diseases and atherosclerosis. Curcumin, a natural polyphenol derived from Curcuma longa, offers a promising approach to inhibit NLRP3-induced inflammation owing to its multi-targeted actions and excellent safety profile. Preclinical models have demonstrated that curcumin inhibits nuclear factor kappa‑light‑chain‑enhancer of activated B cells (NF-κB) signaling, reduces mitochondrial reactive oxygen species (ROS) generation, and suppresses caspase-1 activation and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) assembly, thereby inhibiting inflammasome activation. Curcumin has successfully prevented IL-1β-induced biological effects, tissue damage, and clinical manifestations in models of arthritis, colitis, and Alzheimer's disease (AD). In addition, advanced nanoformulations and structural analogs have enhanced their bioavailability and therapeutic reach. Here, we present a mechanistically focused, curcumin-oriented review synthesizing current knowledge on the NLRP3 inflammasome and its role in chronic inflammatory diseases. We also critically evaluated nanoformulations, curcumin analogs, and combination therapies and integrated evidence from rheumatologic, gastrointestinal, neurodegenerative, metabolic, and cardiovascular models. Furthermore, we explored the molecular mechanisms underlying the therapeutic effects of curcumin and highlighted the challenges of its clinical translation, offering insights for designing precision anti-inflammasome strategies to advance inflammation therapeutics.