Nitric Oxide as a Target for Phytochemicals in Anti-Neuroinflammatory Prevention Therapy

Abstract

Nitric oxide (NO) is a neurotransmitter that mediates the activation and inhibition of inflammatory cascades. Even though physiological NO is required for defense against various pathogens, excessive NO can trigger inflammatory signaling and cell death through reactive nitrogen species-induced oxidative stress. Excessive NO production by activated microglial cells is specifically associated with neuroinflammatory and neurodegenerative conditions, such as Alzheimer’s and Parkinson’s disease, amyotrophic lateral sclerosis, ischemia, hypoxia, multiple sclerosis, and other afflictions of the central nervous system (CNS). Therefore, controlling excessive NO production is a desirable therapeutic strategy for managing various neuroinflammatory disorders. Recently, phytochemicals have attracted considerable attention because of their potential to counteract excessive NO production in CNS disorders. Moreover, phytochemicals and nutraceuticals are typically safe and effective. In this review, we discuss the mechanisms of NO production and its involvement in various neurological disorders, and we revisit a number of recently identified phytochemicals which may act as NO inhibitors. This review may help identify novel potent anti-inflammatory agents that can downregulate NO, specifically during neuroinflammation and neurodegeneration.

Elucidating the Neuroprotective Role of PPARs in Parkinson’s Disease: A Neoteric and Prospective Target

“…Furthermore, NO, a neurotransmitter that is produced through an amino acid, namely L-arginine, has been recognized to perform a distinctive physiological function [ 120 ]. Several investigations have revealed that NO exhibits a key function as a neurotoxic mediator related to mitochondrial impairment in a wide range of incapacitating neurodegenerative conditions, including PD [ 119 ].…”

Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery

“…3-nitrotyrosine and protein carbonyls, these last produced mainly by the action of free radicals on the peptide chain or by oxidation of amino acids, are used as biomarkers of oxidative damage in the brain of AD and MCI [ 18 , 24 , 31 , 32 , 33 ]. NO, also classified as an RNS, is synthesized from L-arginine by three different isoforms of the enzyme NO synthase (NOS), i.e., endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) which catalyze a two-step oxidation of L-arginine to NO and L-citrulline [ 34 , 35 ]. NO is a gaseous molecule, with a lone pair of electrons which can easily diffuse across membranes acting as a vasodilator, neuromodulator, and inflammatory mediator [ 34 ].…”

“…NO, also classified as an RNS, is synthesized from L-arginine by three different isoforms of the enzyme NO synthase (NOS), i.e., endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) which catalyze a two-step oxidation of L-arginine to NO and L-citrulline [ 34 , 35 ]. NO is a gaseous molecule, with a lone pair of electrons which can easily diffuse across membranes acting as a vasodilator, neuromodulator, and inflammatory mediator [ 34 ]. At high concentration, NO reacts with superoxide radical and generates peroxynitrite, contributing to OS.…”

Nitric Oxide: From Gastric Motility to Gastric Dysmotility

“…In this view, physiological compounds, including hormones, able to interfere with NO synthesis, by acting on the specific NOS isoforms expression, or NO-donor drugs can represent useful tools to prevent or treat motor dysfunctions. The importance of this topic is underlined by the emerging researches searching for natural or chemical compounds targeting NO [ 106 , 107 ]. However, it should be remembered that most of the data relating to the effects of NO on GI motor responses derive from studies carried out in animals and caution is mandatory when transferring them to humans.…”