Synergistic Effects of Polyphenol-Terpenoid Combinations on NLRP3 Inflammasome-Mediated Neuroinflammation: A Mini Review
Paul Chinwuba *
Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, P.M.B. 410001, Nsukka, Enugu State, Nigeria.
Chimaobi O. Ugorji
Department of Science Laboratory Technology, Faculty of Physical Sciences, University of Nigeria, P.M.B. 410001, Nsukka, Enugu State, Nigeria.
Daniel L. Ajaghaku
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Agbani, Enugu State, Nigeria.
Winifred O. Amattah
Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, P.M.B. 410001, Nsukka, Enugu State, Nigeria.
Amara A. Ajaghaku
Department of Pharmacognosy and Traditional Medicine, Faculty of Pharmaceutical Sciences, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria and International Institute for Pharmaceutical Research and Innovation, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria.
Onyesife C. Obiageli
Department of Science Laboratory Technology, Faculty of Physical Sciences, University of Nigeria, P.M.B. 410001, Nsukka, Enugu State, Nigeria.
Zogini U. Confidence
Department of Pure and Industrial Chemistry, Faculty of Physical Sciences, University of Nigeria, P.M.B. 410001, Nsukka, Enugu State, Nigeria.
Victor T. Ezeifeh
Department of Internal Medicine, University of Port Harcourt Teaching Hospital, River State, Nigeria.
Okoro O. Kingsley
Department of Pharmacology and Therapeutics, Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Nnewi-Campus, Nnewi, Nigeria.
*Author to whom correspondence should be addressed.
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.
Keywords: Polyphenols, terpenoids, NLRP3 inflammasome, neuroinflammation, synergistic effects, natural compounds, neurological disorders