Synergistic Effects of Polyphenol-Terpenoid Combinations on NLRP3 Inflammasome-Mediated Neuroinflammation: A Mini Review

Abstract

Neuroinflammation driven by the NLRP3 inflammasome is a key mechanism in many neurological disorders. While plant-derived polyphenols and terpenoids individually show anti-inflammatory potential, their synergistic effects remain underexplored. This review highlights the enhanced efficacy of polyphenol-terpenoid combinations in inhibiting NLRP3-mediated neuroinflammation through complementary pathways. Preclinical studies demonstrate that such pairs like quercetin with limonene or curcumin with ar-turmerone more effectively reduce pro-inflammatory cytokines, microglial activation, and oxidative stress than single compounds. However, clinical translation faces challenges including optimal dosing, formulation, and CNS delivery. Future research should focus on identifying effective combinations, elucidating their mechanisms, and validating their therapeutic potential in clinical trials to develop novel treatments for neuroinflammatory diseases.