Apocynin, a plant-derived, cartilage-saving drug, might be useful in the treatment of rheumatoid arthritis

Lafeber, F.P.; Beukelman, C.J.; Worm, Edwin van den; Roy, J. L. A. M. Van; Vianen, M. E.; Roon, J. A. G. Van; Dijk, Hans van; Bijlsma, J. W. J.

doi:10.1093/rheumatology/38.11.1088

Cited by 80 publications

(47 citation statements)

References 27 publications

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“…This botanical compound is derived from the root of Picrorhiza kurroa (Dodd-O and Pearse, 2000) and has been used as a Chinese medicinal herb for treatment of a number of infectious and inflammatory diseases (Hougee et al, 2006;Kim-Mitsuyama et al, 2005;Lafeber et al, 1999). Studies from our laboratory showed the ability for apocynin to protect against delayed neuronal death induced by global cerebral ischemia in the gerbil .…”

Section: Discussionmentioning

confidence: 98%

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Miller

Sun

2007

Brain Research

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Excess production of reactive oxygen species (ROS) is an important mechanism underlying the pathogenesis of a number of neurodegenerative diseases including Parkinson's disease (PD) which is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Exposure to paraquat, an herbicide with structure similar to the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP + ), has been shown to produce PD-like symptoms. Despite previous focus on the dopaminergic neurons and signaling pathways involved in their cell death, recent studies have implicated microglial cells as a major producer of ROS for damaging neighboring neurons. In this study, we examined the source of ROS and the underlying signaling pathway for paraquat-induced cytotoxicity to BV-2 microglial cells. Paraquat-induced ROS production (including superoxide anions) in BV-2 cells was accompanied by translocation of the p67phox cytosolic subunit of NADPH oxidase to the membrane. Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol. Apocynin and DPI also rescued cells from paraquat-induced toxicity. The inhibitors for protein kinase C delta (PKCδ) or extracellular signal-regulated kinases (ERK1/2) could partially attenuate paraquat-induced ROS production and cell death. Rottlerin, a selective PKCδ inhibitor, also inhibited paraquat-induced translocation of p67phox. Taken together, this study demonstrates the involvement of ROS from NADPH oxidase in mediating paraquat cytotoxicity in BV-2 microglial cells and this process is mediated through PKCδ-and ERK-dependent pathways.

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Section: Discussionmentioning

confidence: 98%

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Miller

Sun

2007

Brain Research

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“…Although therapeutic strategies focusing on the elimination of superoxide have been developed in animal models and in clinical cases, the effects of such reagents are still unclear [11,[30][31][32]. Therefore, in this study, we investigated whether inhalation of apocynin may influence hydrogen peroxide, nitrite and nitrate concentrations in airways in healthy subjects.…”

mentioning

confidence: 99%

“…Additionally, no changes in blood differential counts have been noticed. This may suggest that nebulized apocynin does not diffuse into the blood, and acts locally [32,57].…”

mentioning

confidence: 99%

Apocynin decreases hydrogen peroxide and nirtate concentrations in exhaled breath in healthy subjects

Stefańska

Sokołowska

Sarniak

et al. 2010

Pulmonary Pharmacology & Therapeutics

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ARTICLE IN PRESS AbstractThe imbalance between reactive oxygen species (ROS) synthesis and antioxidants might be involved in the pathogenesis of many inflammatory diseases. NADPH oxidase, an enzyme responsible for ROS production, may represent an attractive therapeutic target to inhibit for the treatment of these diseases.Apocynin is an inhibitor of activation of NADPH oxidase complex present in the inflammatory cells.In double blind, placebo controlled, cross-over study, we investigated the effect of nebulized apocynin on ROS synthesis in 10 nonsmoking healthy volunteers. Apocynin (6 ml of 0.5 mg/ml) was administered by nebulization and its effects on H 2 O 2 , NO 2 -and NO 3 -generation were assessed after 30, 60 and 120 minutes by collecting exhaled breath condensate (EBC) samples using an EcoScreen analyzer. Additionally, respiratory parameters have been evaluated, utilizing spirometry and DLCO. We also analyzed peripheral blood differential counts and NO 2 -serum level, cough scale control and blood pressure as safety parameters. Thus, as apocynin significantly influence ROS concentration, it might have also antiinflammatory properties. As it is safe, it may have a potential to become a drug in airway inflammatory diseases treatment.

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“…Several microorganisms are able to convert ferulic acid to a wide range of aromatic compounds (Figure1). These include the following species: Aspergillus, Bacillus, Candida, Corynespora, Fusarium, Pseudomonas and many more (Dodd-o and Pearse, 2000;Engels et al, 1992;Lafeber et al, 1999;Pearse and Dodd-o, 1999;Peters et al, 2001;van den Worm et al, 2001;Walton et al, 2000). The major pathways of metabolism can be summarized as: i) Nonoxidative decarboxylation to give 4-vinylguaiacol (4-hydroxy-3-methoxystyrene) (Rosazza et al, 1995;Lee et al, 1998;Donaghy et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the pharmaceutical use of steroidal drugs is becoming increasingly controversial, owing to multiple side-effects, creating a need for new and safe alternative antiinflammatory agents (Lafeber et al, 1999;van den Worm et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Bioconversion of ferulic acid and 4-vinylguaiacol by a white-rot fungus isolated from decaying wood

Mabinya¹,

Mafunga²,

Br³

2010

Afr. J. Biotechnol.

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A white rot fungus isolated from decaying wood was investigated for its ability to convert ferulic acid to various valuable products. The fungus is able to convert ferulic acid to 4-vinylguaiacol, which is then metabolized further to acetovanillone. Both products have potential use in the chemical manufacturing and pharmaceutical industries and these results contribute to our knowledge of the biotransformation of ferulic acid.

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Apocynin, a plant-derived, cartilage-saving drug, might be useful in the treatment of rheumatoid arthritis

Cited by 80 publications

References 27 publications

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Cytotoxicity of paraquat in microglial cells: Involvement of PKCδ- and ERK1/2-dependent NADPH oxidase

Apocynin decreases hydrogen peroxide and nirtate concentrations in exhaled breath in healthy subjects

Bioconversion of ferulic acid and 4-vinylguaiacol by a white-rot fungus isolated from decaying wood

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