Resveratrol and the NLRP3 Inflammasome: Unlocking the Anti-inflammatory Potential of a Natural Compound

Chronic inflammation is the basis of various diseases, including inflammatory bowel disease, neurodegenerative diseases, and cardiometabolic disorders. NLRP3 is a key player in controlling Interleukin-1β (IL-1β) and Interleukin-18 (IL-18) maturation and pyroptosis via its NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. This review will assess the mechanistic and therapeutic opportunity of resveratrol in restraining the NLRP3 inflammasome activation.

A search of experimental and preclinical studies examining the impact of resveratrol on oxidative stress, inflammatory signaling, mitochondrial activity, and inflammasome activation in various disease models was performed.

Resveratrol reduces oxidative stress by regulating reactive oxygen species-mediated nuclear factor erythroid 2-related factor 2 signaling and suppressing toll-like receptor 4 (TLR4) /nuclear factor kappa B signaling (NF-κB). It maintains mitochondrial integrity by activating sirtuin 1 and AMP-activated protein kinase signalling. In models of acute lung injury, bronchitis, diabetic nephropathy, and neurodegeneration, resveratrol can suppress the expression of NLRP3, caspase-1, and IL-1β, promote autophagy, and prevent dopaminergic neurons through the PINK1/Parkin/NLRP3 pathway. Additionally, it enhances intestinal barrier integrity in dextran sulfate sodium-induced colitis and suppresses inflammasome-mediated inflammation.

These results suggest that resveratrol regulates the priming and activation stages of NLRP3 inflammasome signaling by inhibiting oxidative stress, mitochondrial dysfunction, and inflammatory cascades based on redox signaling. Nanoparticle preparations and structural analogs, such as pterostilbene, improve stability, bioavailability, and specific delivery.

Resveratrol is a potential natural therapeutic agent for managing NLRP3 inflammasomemediated inflammation, and its efficacy is enhanced when administered in optimal formulations and combined with conventional anti-inflammatory agents.