Monoterpene-rich essential oils as natural NRF2 activators: Chemistry, mechanism and antioxidant effects

Background Currently, monoterpene-rich essential oils (MREOs), natural products from aromatic plants, have emerged as potent modulators of redox-sensitive signaling pathways, especially the nuclear factor erythroid 2–related factor 2 (NRF2) signaling pathway. MREOs scavenge free radicals and activate the NRF2 pathway, making them notable antioxidants. The NRF2 transcription factor regulates both cellular antioxidant defense mechanisms and redox homeostasis. The NRF2-inducing activities and therapeutic effects of MREOs in oxidative stress-related diseases have been linked to their complex mixtures of bioactive monoterpenes such as limonene, linalool, geraniol, citronellol, citral, carvacrol, β-myrcene, thymol, 1,8-cineole, and many more. Methods This review explores the chemistry of MREOs, their molecular mechanisms in modulating the NRF2 signaling pathway, and their antioxidant effects in oxidative stress-related disorders. It examines the chemical and biochemical basis of their interactions and their therapeutic and pharmacological potential. Results Owing to the fact that most of the constituent functional groups are electrophilic or redox-active, electrophilic modification of Kelch-like ECH-associated protein 1 (KEAP1), ROS-mediated signaling, and kinase pathway modulation have been found as common mechanisms of action of NRF2-inducing MREOs. Among others, NRF2-activating MREOs such as coriander, lavender, geranium, spearmint, orange, tea tree, oregano, thyme, and eucalyptus oils have specifically demonstrated significant antioxidant-based therapeutic effects in neurodegeneration, inflammation, metabolic dysfunction, cancer, and oxidative stress-mediated diseases. Conclusion MREOs, as natural NRF2 activators with chemical diversity, offer promising avenues for redox-based interventions and natural product drug discovery.