Apocynin

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ImageFile=Apocynin.pngImageSize=150px
IUPACName=1-(4-Hydroxy-3-methoxyphenyl)ethanone
OtherNames=4'-Hydroxy-3'-methoxyacetophenone
Acetovanillone
Section1= Chembox Identifiers
CASNo=498-02-2
PubChem=2214
SMILES=CC(=O)C1=CC(=C(C=C1)O)OC
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Formula=C₉H₁₀O₃
MolarMass=166.174
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MeltingPtC=115
BoilingPt=
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Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. It has been isolated from a variety of plant sources and is being studied for its variety of pharmacological properties.

History

Apocynin was first described by Oswald Schmiedeberg, a German pharmacologist, in 1883 and was first isolated from the root of Canadian hemp ("Apocynum cannabinum"). At the time, this plant was already used for its known effectiveness against edema and heart problems. In 1971, apocynin was also isolated from "Picrorhiza kurroa", a small plant that grows at high altitudes in the western Himalayas. "P. kurroa" was used for ages as a treatment for liver and heart problems, jaundice, and asthma. In 1990, Simons et al. isolated apocynin to a pharmacologically useful level using an actively guided isolation procedure. Apocynin’s observed anti-inflammatory capabilities proved to be a result of its ability to selectively prevent the formation of free radicals, oxygen ions, and peroxides in the body. Apocynin has since been extensively studied to help determine its disease-fighting capabilities and applications.

Physical properties

Apocynin is a solid with a melting point of 115° C and the faint odor of vanilla. It is soluble in hot water, alcohol, benzene, chloroform, and ether.

Mode of action

NADPH oxidase is an enzyme that effectively reduces O₂ to superoxide (O₂^–•), which can be used by the immune system to kill bacteria and fungi. Apoycnin is an inhibitor of NADPH oxidase activity and thus is effective in preventing the production of the superoxide in human white blood cells or neutrophilic granulocytes. It does not however obstruct the phagocytic or other defense roles of Granulocytes. Due to the selectivity of its inhibition, apocynin can be widely used as an inhibitor of NADPH oxidase without interfering in other aspects of the immune system.

Apocynin was used to determine whether ionic activation due to proton flux across the membrane of renal medulla cells was coupled to NADPH oxidase production of superoxide. Apoycnin was introduced to the cells and completely blocked the production of superoxide, and was a key component in determining that the proton outflow was responsible for the activation of NADPH oxidase. [Li, N., Zhang, G., Yi, F.X., Zou, A.P., & Li, P.L. Activation of NAD(P)H oxidase by outward movements of H+ ions in renal medullary thick ascending limb of Henle. American Journal of Physiology-Renal Physiology 289.5 (2005): 1048-56.]

Potential use in medical treatments

*Anti-arthritic: Neutrophils are a key component of the pathogenesis of collagen induced arthritis and in the mechanisms that lead to the start of inflammation of the joints. The action of apocynin reduces the presence of such cells before the inflammation has begun but it is unable to reverse inflammation that is already present. [ Hart, B.A., Simons, J.M ., Knaan –Shanzer, S., Bakker, N.P., & Labadie, R.P. Antiarthritic activity of the newly developed neutrophil oxidative burst antagonist apocynin. Free Radicals in Biology and Medicine 9.2 (1990): 127-31.]
*Bowel disease: Apocynin treatment in rats has been proven to lessen damage in the colon as wells as the enzymatic activity of myeloperoxidase which is associated with inflammation. In addition, apocynin also decreased the number of macrophages and polymorphonuclear leukocytes in the colon. [Palmen M.J.H.J., Beukelman C.J., Mooij R.G.M., Pena A.S., & van Rees E.P. Anti-inflammatory effect of apocynin, a plant-derived NADPH oxidase antagonist, in acute experimental colitis. The Netherlands Journal of Medicine 47.2 (1995): 41-41]
*Anti-asthmatic: The glucoside of apocynin, androsen, is being investigated for the treatment of asthma for has been shown to prevent bronchial obstruction in guinea pigs. It is believed that the anti-asthmatic quality of apocynin comes from its interference with certain inflammatory processes. [Van den Worm, E., Beukelman, CJ., Van den Berg, AJ., Kroes, BH., Labadie, RP., & Van Dijk, H. Effects of methoxylation of apocynin and analogs on the inhibition of reactive oxygen species production by stimulated human neutrophils. European Journal of Pharmacology 433.2 (2001): 225-30.]
*Atherosclerosis: Apocynin is used in the treatment of atherosclerosis in order to prevent the activity of NADPH oxidase activity, halting the production of reactive oxidative species. In effect, this inhibition stops initiation of disease in the endothelial cells. [Peters, E.A., Hiltermann, J.T., & Stolk, J. Effects of methoxylation of apocynin and analogs on the inhibition of reactive oxygen species production by stimulated human neutrophils. Free Radicals in Biology and Medicine 31.11 (2001): 1442-7.]
*Familial ALS: Apocynin extended the lives of mutant mice and reduced glial cell toxicity of cultured cells lines with a defective Superoxide Dismutase-1 (SOD1) gene -- a genetic defect found in some people with hereditary amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). Researchers believe the benefit derives from a newly discovered role for SOD1 as a self-regulating redox sensor for NADPH oxidase-derived O2• production. In humans, apocynin may trigger chronic granulomatous disease, but the findings in mice may point to new drug targets for hereditary ALS. [Harraz, MM., Marden, JJ., Zhou1, W., Zhang, Y., Williams, A., Sharov, VS., Nelson, K., Luo, M., Paulson, H., Schöneich, C. and Engelhardt JF. [http://content.the-jci.org/articles/view/34060 SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model] . J. Clin. Invest. doi:10.1172/JCI34060. Jan 24, 2008]

References