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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

Inhibition of microglia Nox2 by metabolically activated apocynin. Receptor-mediated activation of microglia cells induces production of reactive oxygen species and release of myeloperoxidase (MPO). The MPO-catalyzed reaction of apocynin with H2O2 leads to production of a reactive intermediate that stabilizes by binding to free thiol groups, for example, GSH, or by dimerization. Dimeric apocynin (diapocynin) inhibits Nox2 activity.
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fig2: Inhibition of microglia Nox2 by metabolically activated apocynin. Receptor-mediated activation of microglia cells induces production of reactive oxygen species and release of myeloperoxidase (MPO). The MPO-catalyzed reaction of apocynin with H2O2 leads to production of a reactive intermediate that stabilizes by binding to free thiol groups, for example, GSH, or by dimerization. Dimeric apocynin (diapocynin) inhibits Nox2 activity.

Mentions: It can be envisaged that components of chemically complex plant extracts can interfere with the read-out assay at multiple levels and may also exert nonspecific effects such as killing of the PMN or scavenging of the oxyradicals. This implies that successful activity-guided purification needs to be well focused and carefully controlled for nonspecific effects to avoid false positive results. Notwithstanding these hurdles, we were able to demonstrate a highly specific activity of apocynin in the assay. Apocynin was found to be metabolically activated in an MPO-catalyzed reaction with H2O2 [7] forming a symmetrical dimer, diapocynin [8] (Figure 2). The observation that the reaction intermediate could be trapped with GSH led us to hypothesize that metabolically activated apocynin might block the formation of thiol bridges between the membrane-bound and cytosolic components that assemble functional Nox2. It was later found, however, that diapocynin directly inhibits Nox2 superoxide production and that this activity is independent of MPO [8]. An important finding with apocynin has been that it inhibits the oxidative burst of PMNs, without impeding the intracellular killing of bacteria. This implies that treatment with apocynin may prevent collateral damage to tissues infiltrated by activated PMN without impeding their bactericidal function.


Apocynin, a low molecular oral treatment for neurodegenerative disease.

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

Inhibition of microglia Nox2 by metabolically activated apocynin. Receptor-mediated activation of microglia cells induces production of reactive oxygen species and release of myeloperoxidase (MPO). The MPO-catalyzed reaction of apocynin with H2O2 leads to production of a reactive intermediate that stabilizes by binding to free thiol groups, for example, GSH, or by dimerization. Dimeric apocynin (diapocynin) inhibits Nox2 activity.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Inhibition of microglia Nox2 by metabolically activated apocynin. Receptor-mediated activation of microglia cells induces production of reactive oxygen species and release of myeloperoxidase (MPO). The MPO-catalyzed reaction of apocynin with H2O2 leads to production of a reactive intermediate that stabilizes by binding to free thiol groups, for example, GSH, or by dimerization. Dimeric apocynin (diapocynin) inhibits Nox2 activity.
Mentions: It can be envisaged that components of chemically complex plant extracts can interfere with the read-out assay at multiple levels and may also exert nonspecific effects such as killing of the PMN or scavenging of the oxyradicals. This implies that successful activity-guided purification needs to be well focused and carefully controlled for nonspecific effects to avoid false positive results. Notwithstanding these hurdles, we were able to demonstrate a highly specific activity of apocynin in the assay. Apocynin was found to be metabolically activated in an MPO-catalyzed reaction with H2O2 [7] forming a symmetrical dimer, diapocynin [8] (Figure 2). The observation that the reaction intermediate could be trapped with GSH led us to hypothesize that metabolically activated apocynin might block the formation of thiol bridges between the membrane-bound and cytosolic components that assemble functional Nox2. It was later found, however, that diapocynin directly inhibits Nox2 superoxide production and that this activity is independent of MPO [8]. An important finding with apocynin has been that it inhibits the oxidative burst of PMNs, without impeding the intracellular killing of bacteria. This implies that treatment with apocynin may prevent collateral damage to tissues infiltrated by activated PMN without impeding their bactericidal function.

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