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Apocynin, a low molecular oral treatment for neurodegenerative disease.

't Hart BA, Copray S, Philippens I - Biomed Res Int (2014)

Bottom Line: Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases.Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida.Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ Rijswijk, The Netherlands ; Department of Neuroscience, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

ABSTRACT
Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases. This may imply that patients affected by a neurodegenerative disease may benefit from treatment with selective inhibitors of innate immune activity. Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida. Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose.

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Related in: MedlinePlus

Reactive oxygen species produced in the phagocyte oxidative burst. MPO: myeloperoxidase; NOS: nitric oxide (NO) synthase.
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fig1: Reactive oxygen species produced in the phagocyte oxidative burst. MPO: myeloperoxidase; NOS: nitric oxide (NO) synthase.

Mentions: The read-out assay we used was based on the generation of luminol-enhanced chemiluminescence by human PMN stimulated with zymosan opsonized in human serum. The essence of the assay is that the serum-opsonized yeast particles stimulate the PMN via surface-exposed receptors of immunoglobulins or complement factors. The activation signals relayed via these receptors lead to the emptying of cytoplasmic granules (degranulation) and the assembly of the phagocyte NADPH oxidase Nox2. The Nox2 enzyme complex is assembled from membrane-bound (gp91phox, p22phox) and cytoplasmic (p40phox, p47phox, p67phox, and Rac2) subunits [3]. The assembly process involves phosphorylation of subunits by specific kinases and formation of thiol-bridges. The assembled complex takes up electrons from NADPH and transfers these onto free molecular oxygen leading to formation of superoxide anion (O2−; one electron reduction) and hydrogen peroxide (H2O2; two electron reduction). Both oxidants have cytotoxic activity as could be shown using red blood cells from different species [4]. The oxidative burst of PMN comprises a cascade of strongly reactive oxygen species, collectively indicated as ROS (Figure 1). By reaction of O2− with nitric oxide the strongly cytotoxic peroxynitrite is formed. In the presence of Fe2+ ions H2O2 is converted into highly reactive hydroxyl radicals (OH•), which via peroxidation of membrane lipids affect the fluidity of cell membranes. Myeloperoxidase released by degranulation of the PMN catalyzes the reaction of H2O2 with halide molecules (Cl2, Br2, and J2) forming highly toxic hypohalides (OCl−, OBr−, and OJ−). ROS are essential components of the intracellular killing of phagocytosed microbes, but when released into the extracellular milieu they are important mediators of the tissue destructive activity of activated PMNs [5, 6].


Apocynin, a low molecular oral treatment for neurodegenerative disease.

't Hart BA, Copray S, Philippens I - Biomed Res Int (2014)

Reactive oxygen species produced in the phagocyte oxidative burst. MPO: myeloperoxidase; NOS: nitric oxide (NO) synthase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129132&req=5

fig1: Reactive oxygen species produced in the phagocyte oxidative burst. MPO: myeloperoxidase; NOS: nitric oxide (NO) synthase.
Mentions: The read-out assay we used was based on the generation of luminol-enhanced chemiluminescence by human PMN stimulated with zymosan opsonized in human serum. The essence of the assay is that the serum-opsonized yeast particles stimulate the PMN via surface-exposed receptors of immunoglobulins or complement factors. The activation signals relayed via these receptors lead to the emptying of cytoplasmic granules (degranulation) and the assembly of the phagocyte NADPH oxidase Nox2. The Nox2 enzyme complex is assembled from membrane-bound (gp91phox, p22phox) and cytoplasmic (p40phox, p47phox, p67phox, and Rac2) subunits [3]. The assembly process involves phosphorylation of subunits by specific kinases and formation of thiol-bridges. The assembled complex takes up electrons from NADPH and transfers these onto free molecular oxygen leading to formation of superoxide anion (O2−; one electron reduction) and hydrogen peroxide (H2O2; two electron reduction). Both oxidants have cytotoxic activity as could be shown using red blood cells from different species [4]. The oxidative burst of PMN comprises a cascade of strongly reactive oxygen species, collectively indicated as ROS (Figure 1). By reaction of O2− with nitric oxide the strongly cytotoxic peroxynitrite is formed. In the presence of Fe2+ ions H2O2 is converted into highly reactive hydroxyl radicals (OH•), which via peroxidation of membrane lipids affect the fluidity of cell membranes. Myeloperoxidase released by degranulation of the PMN catalyzes the reaction of H2O2 with halide molecules (Cl2, Br2, and J2) forming highly toxic hypohalides (OCl−, OBr−, and OJ−). ROS are essential components of the intracellular killing of phagocytosed microbes, but when released into the extracellular milieu they are important mediators of the tissue destructive activity of activated PMNs [5, 6].

Bottom Line: Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases.Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida.Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ Rijswijk, The Netherlands ; Department of Neuroscience, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

ABSTRACT
Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases. This may imply that patients affected by a neurodegenerative disease may benefit from treatment with selective inhibitors of innate immune activity. Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida. Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose.

Show MeSH
Related in: MedlinePlus