Apocynin, also known as acetovanillone, is a natural

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

structurally related to

vanillin Vanillin is an organic compound with the molecular formula . It is a phenolic aldehyde. Its functional groups include aldehyde, hydroxyl, and ether. It is the primary component of the extract of the vanilla bean. Synthetic vanillin is now used ...

. 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 Johann Ernst Oswald Schmiedeberg (10 October 1838 – 12 July 1921) was a Baltic German pharmacologist. In 1866 he earned his medical doctorate from the University of Dorpat with a thesis concerning the measurement of chloroform in blood, before ...

, a German pharmacologist, in 1883 and was first isolated by Horace Finnemore, in 1908, from the root of Canadian hemp (''

Apocynum cannabinum ''Apocynum cannabinum'' (dogbane, amy root, hemp dogbane, prairie dogbane, Indian hemp, rheumatism root, or wild cotton) is a perennial herbaceous plant that grows throughout much of North America—in the southern half of Canada and throughou ...

''). At the time, this plant was already used for its known effectiveness against

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

and heart problems. In 1971, apocynin was also isolated from ''Picrorhiza kurroa'', a small plant that grows at high altitudes in the western

Himalayas The Himalayas, or Himalaya (; ; ), is a mountain range in Asia, separating the plains of the Indian subcontinent from the Tibetan Plateau. The range has some of the planet's highest peaks, including the very highest, Mount Everest. Over 100 ...

. ''P. kurroa'' was used for ages as a treatment for liver and heart problems,

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

, and

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

. 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 In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spont ...

, oxygen ions, and

peroxide In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen p ...

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

vanilla Vanilla is a spice derived from orchids of the genus ''Vanilla (genus), Vanilla'', primarily obtained from pods of the Mexican species, flat-leaved vanilla (''Vanilla planifolia, V. planifolia''). Pollination is required to make the p ...

. It is soluble in hot water,

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

, and

ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...

Mode of action

NADPH oxidase NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...

is an enzyme that effectively reduces O₂ to

superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of the ...

(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

granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...

s. 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

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. The mechanism of action of apocynin is not understood. In the experimental studies, apocynin is shown to dimerize and form

diapocynin Diapocynin is a dimer of apocynin. Synthesis Diapocynin is synthesized by the activation of apocynin with ferrous sulfate and sodium persulfate. Similar to apocynin, it is shown to have some beneficial effects against oxidative stress and reducin ...

. Although, diapocynin seems to have beneficial effect in reducing

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

and anti-inflammatory properties, it is still yet to be shown as biologically relevant molecule. Biotransformation of apocynin predominantly leads to glycosylated form of apocynin. Another molecule that is shown to form under experimental conditions is

nitroapocynin Nitroapocynin is a mono-nitrated form of apocynin. Synthesis Apocynin can be nitrated with sodium nitrate and acidic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate in acetonitrile Acetonitrile, often abbreviated MeCN (methyl c ...

Research

Small scale early stage clinical trials for apocynin were conducted for

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

(COPD) in 2011 and asthma in 2012 but they did not progress any further. Other preliminary pre-clinical research includes: * Anti-arthritic: Neutrophils are a key component of the pathogenesis of

collagen-induced arthritis Collagen-induced arthritis (CIA) is a condition induced in mice (or rats) to study rheumatoid arthritis. CIA is induced in mice by injecting them with an emulsion of complete Freund's adjuvant and type II collagen Type II collagen is the basis ...

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, androsin, 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 oxygen 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 cell Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...

toxicity of cultured cells lines with a defective

superoxide dismutase 1 Superoxide dismutase u-Zn'' also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the ''SOD1'' gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis, fam ...

(SOD1) gene—a genetic defect found in some people with hereditary

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

(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

-derived O2• production. The findings in mice may point to new drug targets for hereditary ALS. * Skin stem cells: Apocynin promotes the synthesis of collagen 17 and by doing this it increases the survival of the mother cells derived from stem cells.

References

{{Reflist O-methylated natural phenols Vanilloids Aromatic ketones Catechols