Abstract

FROM OXIDATIVE STRESS TO NEUROINFLAMMATION: PHARMACOLOGICAL TARGETING OF THE NRF2–NF-KB–NLRP3 AXIS BY PLANT-DERIVED BIOACTIVE COMPOUNDS

Aishwarya T. V.*

Abstract

Neurodegenerative disorders present with progressive neuronal dysfunction and loss and are increasingly recognized as conditions in which oxidative stress, mitochondrial impairment and chronic neuroinflammation interact. Reactive oxygen species can activate inflammatory signaling, while persistent activation of inflammatory pathways can further increase oxidative injury, forming a self-amplifying pathological cycle. Nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF- κB), and the nod- like receptor family pyrin domain containing 3 (NLRP3) inflammasome have emerged as interconnected pharmacological targets. Plantderived bioactive compounds are of particular interest as many possess antioxidant and anti-inflammatory activities and may modulate several signaling pathways simultaneously. This review examines the mechanistic relationship between oxidative stress and neuroinflammation, focusing on the Nrf2–NF-κB– NLRP3 axis, and summarizes evidence for representative phytochemicals including curcumin, quercetin, resveratrol, berberine, epigallocatechin-3-gallate, baicalein/baicalin, ginsenosides and apigenin. Evidence from cellular and experimental animal models is considered alongside pharmacokinetic limitations, bioavailability, safety, standardization and translational challenges. Particular attention is given to the potential that coordinated modulation of antioxidant and inflammatory pathways may provide a pharmacological strategy distinct from single-target approaches. Future research should prioritize well- characterized extracts or compounds, target engagement biomarkers, rigorous pharmacokinetic studies and adequately designed clinical investigations.

Keywords: Nrf2; NF-κB; NLRP3 inflammasome; oxidative stress; neuroinflammation; phytochemicals; neuroprotection; medicinal plants; neurodegenerative disorders; pharmacology.