Apocynin
Encyclopedia
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.
, 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 peroxide
s in the body. Apocynin has since been extensively studied to help determine its disease-fighting capabilities and applications.
. It is soluble in hot water, alcohol
, benzene
, chloroform
, and ether
.
is an enzyme that effectively reduces O2 to superoxide
(O2–•), which can be used by the immune system to kill bacteria and fungi. Apocynin 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. Apocynin 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.
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
structurally related to vanillin
Vanillin
Vanillin is a phenolic aldehyde, an organic compound with the molecular formula C8H8O3. Its functional groups include aldehyde, ether, and phenol. It is the primary component of the extract of the vanilla bean. It is also found in Leptotes bicolor, roasted coffee and the Chinese red pine...
. 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 SchmiedebergOswald Schmiedeberg
Oswald Schmiedeberg was a Baltic German pharmacologist.Schmiedeberg was born at Gut Laidsen in the Imperial Russian province of Courland. In 1866 he earned his medical doctorate from the University of Dorpat with a thesis concerning the measurement of chloroform in blood. Afterwards he was an...
, 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
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
and heart problems. In 1971, apocynin was also isolated from Picrorhiza kurroa, a small plant that grows at high altitudes in the western Himalayas
Himalayas
The Himalaya Range or Himalaya Mountains Sanskrit: Devanagari: हिमालय, literally "abode of snow"), usually called the Himalayas or Himalaya for short, is a mountain range in Asia, separating the Indian subcontinent from the Tibetan Plateau...
. P. kurroa was used for ages as a treatment for liver and heart problems, jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, and asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
. 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
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
, oxygen ions, and peroxide
Peroxide
A peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...
s 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 vanillaVanilla
Vanilla is a flavoring derived from orchids of the genus Vanilla, primarily from the Mexican species, Flat-leaved Vanilla . The word vanilla derives from the Spanish word "", little pod...
. It is soluble in hot water, alcohol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
, chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
, and ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
.
Mode of action
NADPH oxidaseNADPH oxidase
The NADPH oxidase is a membrane-bound enzyme complex. It can be found in the plasma membrane as well as in the membrane of phagosome.-Subunits:It is made up of six subunits...
is an enzyme that effectively reduces O2 to superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
(O2–•), which can be used by the immune system to kill bacteria and fungi. Apocynin 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
NADPH oxidase
The NADPH oxidase is a membrane-bound enzyme complex. It can be found in the plasma membrane as well as in the membrane of phagosome.-Subunits:It is made up of six subunits...
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. Apocynin 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.
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.
- Bowel disease: Apocynin treatment in rats has been proven to lessen damage in the colon as well 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.
- 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.
- 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.
- Familial ALS: Apocynin extended the lives of mutant mice and reduced glial cellGlial cellGlial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
toxicity of cultured cells lines with a defective Superoxide Dismutase-1 (SOD1SOD1Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or SOD1 is an enzyme that in humans is encoded by the SOD1 gene. SOD1 is one of three human superoxide dismutases.- Function :...
) gene -- a genetic defect found in some people with hereditary amyotrophic lateral sclerosisAmyotrophic lateral sclerosisAmyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
(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 oxidaseNADPH oxidaseThe NADPH oxidase is a membrane-bound enzyme complex. It can be found in the plasma membrane as well as in the membrane of phagosome.-Subunits:It is made up of six subunits...
-derived O2• production. The findings in mice may point to new drug targets for hereditary ALS.