Source: Medical Gas Research

PubMed ID: 42714876

DOI: 10.4103/mgr.MEDGASRES-D-26-00135

Nitric oxide facilitates communication between neurons and induces vasodilation in cerebral blood vessels. However, excess nitric oxide, particularly that derived from the inducible nitric oxide synthase pathway, can trigger neuroinflammation and neuronal death. The present review outlines the mechanisms of the three nitric oxide synthase isoforms (neuronal, inducible, and endothelial) and the consequences of disruptions to their balance. Then, we synthesized experimental evidence on plant- derived compounds, essential oils, isolated phytochemicals, extracts, and food-derived molecules that alter nitric oxide synthase expression or activity and downstream nitric oxide signaling across a range of conditions, including aging, neurodegenerative and autoimmune diseases, stroke, neuropsychiatric disorders, metabolic brain dysfunction, and even development. The majority of plant molecules have been found to attenuate inducible nitric oxide synthase overproduction by obstructing nuclear factor κB-driven inflammatory signals. The effects of these substances on the constitutive isoforms (neuronal and endothelial nitric oxide synthase) are more complex. This complexity is indicative of the challenges associated with fine-tuning nitric oxide signaling therapeutically. Nevertheless, these natural products offer a method of regulating pathological nitric oxide without eliminating its physiological functions. The findings indicate that plant-based modulators of nitric oxide-related signaling pathways have the potential to serve as effective neuroprotective strategies, provided that future research clarifies the isoform-specific actions and the methods for transitioning from laboratory research to clinical application.