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

Int J Mol Sci. 2021 Apr 30;22(9):4771. doi: 10.3390/ijms22094771.

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.

Keywords: medicinal plants; neurodegeneration; neuroinflammation; nitric oxide; phytochemicals; plants derivatives; reactive nitrogen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Drug Discovery
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Molecular Targeted Therapy
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Oxidative Stress / drug effects
  • Phytochemicals / chemistry
  • Phytochemicals / pharmacology*
  • Phytochemicals / therapeutic use
  • Reactive Nitrogen Species / metabolism

Substances

  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Phytochemicals
  • Reactive Nitrogen Species
  • Nitric Oxide