Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms

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Abstract

In the present study we report the preventive effect of apocynin, an active constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2 (Cox-2) synthesis and activity in human adherent monocytes exposed to serum treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly decreases the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) and prevents nuclear factor-κB (NF-κB) activation in stimulated monocytes. Moreover, it reduces intracellular reactive oxygen species (ROS) generation, NADPH oxidase activity in monocyte homogenates and translocation of p47phox subunit in monocyte membranes. p47phox levels are also reduced in lysates of apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely abrogated by GSH provision. Results from this study indicate that apocynin inhibits Cox-2 synthesis and activity induced in monocytes by an increased oxidative tone and provide an explanation for the protective effect exerted by this compound in numerous cell and animal models of inflammation. Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-κB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition.

Original languageEnglish
Pages (from-to)156-165
Number of pages10
JournalFree Radical Biology and Medicine
Volume37
Issue number2
DOIs
Publication statusPublished - Jul 15 2004

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NADPH Oxidase
Cyclooxygenase 2
Oxidation-Reduction
Glutathione
Monocytes
Glutathione Disulfide
Reactive Oxygen Species
Chemical activation
Picrorhiza
Zymosan
Tetradecanoylphorbol Acetate
Animals
Human Activities
acetovanillone
Membranes
Animal Models
Inflammation
Serum

Keywords

  • Apocynin
  • Cox-2
  • Cyclooxygenase 2
  • cyclooxygenase 2
  • diphenyleneiodonium
  • DPI
  • EMSA
  • Free radicals
  • Monocytes
  • NADPH oxidase
  • Nuclear Factor κB
  • Prostaglandin E
  • Reactive oxygen species
  • Reduced/oxidized glutathione ratio

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

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title = "Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms",
abstract = "In the present study we report the preventive effect of apocynin, an active constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2 (Cox-2) synthesis and activity in human adherent monocytes exposed to serum treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly decreases the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) and prevents nuclear factor-κB (NF-κB) activation in stimulated monocytes. Moreover, it reduces intracellular reactive oxygen species (ROS) generation, NADPH oxidase activity in monocyte homogenates and translocation of p47phox subunit in monocyte membranes. p47phox levels are also reduced in lysates of apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely abrogated by GSH provision. Results from this study indicate that apocynin inhibits Cox-2 synthesis and activity induced in monocytes by an increased oxidative tone and provide an explanation for the protective effect exerted by this compound in numerous cell and animal models of inflammation. Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-κB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition.",
keywords = "Apocynin, Cox-2, Cyclooxygenase 2, cyclooxygenase 2, diphenyleneiodonium, DPI, EMSA, Free radicals, Monocytes, NADPH oxidase, Nuclear Factor κB, Prostaglandin E, Reactive oxygen species, Reduced/oxidized glutathione ratio",
author = "Barbieri, {Silvia S.} and Viviana Cavalca and Sonia Eligini and Marta Brambilla and Alessia Caiani and Elena Tremoli and Susanna Colli",
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T1 - Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms

AU - Barbieri, Silvia S.

AU - Cavalca, Viviana

AU - Eligini, Sonia

AU - Brambilla, Marta

AU - Caiani, Alessia

AU - Tremoli, Elena

AU - Colli, Susanna

PY - 2004/7/15

Y1 - 2004/7/15

N2 - In the present study we report the preventive effect of apocynin, an active constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2 (Cox-2) synthesis and activity in human adherent monocytes exposed to serum treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly decreases the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) and prevents nuclear factor-κB (NF-κB) activation in stimulated monocytes. Moreover, it reduces intracellular reactive oxygen species (ROS) generation, NADPH oxidase activity in monocyte homogenates and translocation of p47phox subunit in monocyte membranes. p47phox levels are also reduced in lysates of apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely abrogated by GSH provision. Results from this study indicate that apocynin inhibits Cox-2 synthesis and activity induced in monocytes by an increased oxidative tone and provide an explanation for the protective effect exerted by this compound in numerous cell and animal models of inflammation. Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-κB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition.

AB - In the present study we report the preventive effect of apocynin, an active constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2 (Cox-2) synthesis and activity in human adherent monocytes exposed to serum treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly decreases the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) and prevents nuclear factor-κB (NF-κB) activation in stimulated monocytes. Moreover, it reduces intracellular reactive oxygen species (ROS) generation, NADPH oxidase activity in monocyte homogenates and translocation of p47phox subunit in monocyte membranes. p47phox levels are also reduced in lysates of apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely abrogated by GSH provision. Results from this study indicate that apocynin inhibits Cox-2 synthesis and activity induced in monocytes by an increased oxidative tone and provide an explanation for the protective effect exerted by this compound in numerous cell and animal models of inflammation. Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-κB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition.

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KW - EMSA

KW - Free radicals

KW - Monocytes

KW - NADPH oxidase

KW - Nuclear Factor κB

KW - Prostaglandin E

KW - Reactive oxygen species

KW - Reduced/oxidized glutathione ratio

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