Caffeic acid is an

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. Th ...

that is classified as a

hydroxycinnamic acid Hydroxycinnamic acids (hydroxycinnamates) are a class of aromatic acids or phenylpropanoids having a C6–C3 skeleton. These compounds are hydroxy derivatives of cinnamic acid. In the category of phytochemicals that can be found in food, there ...

. This yellow solid consists of both

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it r ...

ic and

acrylic Acrylic may refer to: Chemicals and materials * Acrylic acid, the simplest acrylic compound * Acrylate polymer, a group of polymers (plastics) noted for transparency and elasticity * Acrylic resin, a group of related thermoplastic or thermosett ...

functional groups. It is found in all plants because it is an intermediate in the

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecul ...

lignin Lignin is a class of complex organic polymers that form key structural materials in the support tissues of most plants. Lignins are particularly important in the formation of cell walls, especially in wood and bark, because they lend rigidity a ...

, one of the principal components of woody plant

biomass Biomass is plant-based material used as a fuel for heat or electricity production. It can be in the form of wood, wood residues, energy crops, agricultural residues, and waste from industry, farms, and households. Some people use the terms bio ...

and its residues.

Natural occurrences

Caffeic acid can be found in the bark of '' Eucalyptus globulus'' the

barley Barley (''Hordeum vulgare''), a member of the grass family, is a major cereal grain grown in temperate climates globally. It was one of the first cultivated grains, particularly in Eurasia as early as 10,000 years ago. Globally 70% of barley p ...

grain ''Hordeum vulgare'' and the herb '' Dipsacus asperoides''. It can also be found in the freshwater fern '' Salvinia molesta'' and in the mushroom ''

Phellinus linteus ''Phellinus linteus'' (Japanese "meshimakobu", Chinese "song gen", Korean "sanghwang", English "mesima", American English "black hoof mushroom") is a mushroom. It is shaped like a hoof, has a bitter taste, and in the wild grows on mulberry trees ...

''.

Occurrences in food

Free caffeic acid can be found in a variety of beverages, including brewed

coffee Coffee is a drink prepared from roasted coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content. It is the most popular hot drink in the world. Seeds of ...

at 0.13 mg per 100 ml and red wine at 2 mg per 100 ml. It is found at relatively high levels in herbs of the mint family, especially

thyme Thyme () is the herb (dried aerial parts) of some members of the genus ''Thymus'' of aromatic perennial evergreen herbs in the mint family Lamiaceae. Thymes are relatives of the oregano genus '' Origanum'', with both plants being mostly indigen ...

, sage and spearmint (at about 20 mg per 100 g), and in spices, such as

Ceylon cinnamon ''Cinnamomum verum'', called true cinnamon tree or Ceylon cinnamon tree, is a small evergreen tree belonging to the family Lauraceae, native to Sri Lanka. The inner bark of several other ''Cinnamomum'' species are also used to make cinnamon, ...

and

star anise ''Illicium verum'' is a medium-sized evergreen tree native to northeast Vietnam and southwest China. A spice commonly called star anise, staranise, star anise seed, star aniseed, star of anise, Chinese star anise, or badian that closely resemb ...

(at about 22 mg per 100 g). Caffeic acid occurs at moderate levels in

sunflower seed The sunflower seed is the seed of the sunflower (''Helianthus annuus''). There are three types of commonly used sunflower seeds: linoleic (most common), high oleic, and sunflower oil seeds. Each variety has its own unique levels of monounsat ...

s (8 mg per 100 g),

apple sauce Apple sauce or applesauce is a purée (not necessarily served as a true sauce) made of apples. It can be made with peeled or unpeeled apples and may be spiced or sweetened. Apple sauce is inexpensive and is widely consumed in North America and s ...

apricot An apricot (, ) is a fruit, or the tree that bears the fruit, of several species in the genus '' Prunus''. Usually, an apricot is from the species '' P. armeniaca'', but the fruits of the other species in ''Prunus'' sect. ''Armeniaca'' are al ...

s and

prune A prune is a dried plum, most commonly from the European plum (''Prunus domestica''). Not all plum species or varieties can be dried into prunes. A prune is the firm-fleshed fruit (plum) of '' Prunus domestica'' varieties that have a high so ...

s (at about 1 mg per 100 g). It occurs at remarkably high levels in

black chokeberry ''Aronia melanocarpa'', called the black chokeberry, is a species of shrubs in the rose family native to eastern North America, ranging from Canada to the central United States, from Newfoundland west to Ontario and Minnesota, south as far as A ...

(141 mg per 100 g). It is also quite high in the South American herb

yerba mate Yerba mate or yerba-maté (''Ilex paraguariensis''; from Spanish ; pt, erva-mate, or ; gn, ka'a, ) is a plant species of the holly genus '' Ilex'' native to South America. It was named by the French botanist Augustin Saint-Hilaire. The lea ...

(150 mg per 100 g based on thin layer chromatography densiometry and HPLC ). It is also found at lower levels in

and rye.

Metabolism

Biosynthesis

Caffeic acid, which is unrelated to

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class. It is mainly recreational drug use, used recreationally as a Nootropic, cognitive enhancer, increasing alertness and attentional perfor ...

, is biosynthesized by

hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...

of coumaroyl ester of

quinic acid Quinic acid is a cyclitol, a cyclic polyol, and a cyclohexanecarboxylic acid. It is a colorless solid that can be extracted from plant sources. Quinic acid is implicated in the perceived acidity of coffee. Occurrence and preparation The compound i ...

(esterified through a side chain alcohol). This hydroxylation produces the caffeic acid ester of

shikimic acid Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower ''shik ...

, which converts to

chlorogenic acid Chlorogenic acid (CGA) is the ester of caffeic acid and (−)-quinic acid, functioning as an intermediate in lignin biosynthesis. The term "chlorogenic acids" refers to a related polyphenol family of esters, including hydroxycinnamic acids ( caf ...

. It is the precursor to

ferulic acid Ferulic acid is a hydroxycinnamic acid, an organic compound with the formula (CH3O)HOC6H3CH=CHCO2H. The name is derived from the genus ''Ferula'', referring to the giant fennel ('' Ferula communis''). Classified as a phenolic phytochemical, ferul ...

coniferyl alcohol Coniferyl alcohol is an organic compound with the formula HO(CH3O)C6H3CH=CHCH2OH. A colourless or white solid, it is one of the monolignols, produced via the phenylpropanoid biochemical pathway. When copolymerized with related aromatic compounds, ...

, and sinapyl alcohol, all of which are significant building blocks in lignin. The transformation to ferulic acid is catalyzed by the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

caffeate ''O''-methyltransferase. Caffeic acid and its derivative caffeic acid phenethyl ester (CAPE) are produced in many kinds of plants. : Dihydroxyphenylalanine ammonia-lyase was presumed to use 3,4-dihydroxy-L-phenylalanine (L-DOPA) to produce trans-caffeate and NH₃. However, the EC number for this purported enzyme was deleted in 2007, as no evidence has emerged for its existence.

Biotransformation

Caffeate ''O''-methyltransferase is an enzyme responsible for the transformation of caffeic acid into

. Caffeic acid and related ''o''-diphenols are rapidly oxidized by ''o''-diphenol oxidases in tissue extracts.

Biodegradation

Caffeate 3,4-dioxygenase is an enzyme that uses caffeic acid and oxygen to produce 3-(2-carboxyethenyl)-''cis'',''cis''-muconate.

Glycosides

3-''O''-caffeoylshikimic acid ( dactylifric acid) and its isomers, are enzymic browning substrates found in dates (''

Phoenix dactylifera ''Phoenix dactylifera'', commonly known as date or date palm, is a flowering plant species in the palm family, Arecaceae, cultivated for its edible sweet fruit called dates. The species is widely cultivated across northern Africa, the Middle Ea ...

'' fruits).

Pharmacology

Caffeic acid has a variety of potential pharmacological effects in ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

'' studies and in animal models, and the inhibitory effect of caffeic acid on cancer cell proliferation by an oxidative mechanism in the human HT-1080

fibrosarcoma Fibrosarcoma (fibroblastic sarcoma) is a malignant mesenchymal tumour derived from fibrous connective tissue and characterized by the presence of immature proliferating fibroblasts or undifferentiated anaplastic spindle cells in a storiform pat ...

cell line has recently been established. Caffeic acid is an

antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...

''in vitro'' and also ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...

''. Caffeic acid also shows immunomodulatory and

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...

activity. Caffeic acid outperformed the other antioxidants, reducing

aflatoxin Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly ''Aspergillus'' species. The fungi grow in soil, decaying vegetation and various staple foodstuffs and commodities such as hay, sweetcorn ...

production by more than 95 percent. The studies are the first to show that oxidative stress that would otherwise trigger or enhance ''

Aspergillus flavus ''Aspergillus flavus'' is a saprotrophic and pathogenic fungus with a cosmopolitan distribution. It is best known for its colonization of cereal grains, legumes, and tree nuts. Postharvest rot typically develops during harvest, storage, and/or ...

'' aflatoxin production can be stymied by caffeic acid. This opens the door to use as a natural

fungicide Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality ...

by supplementing trees with antioxidants. Studies of the carcinogenicity of caffeic acid have mixed results. Some studies have shown that it inhibits

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...

, and other experiments show carcinogenic effects. Oral administration of high doses of caffeic acid in rats has caused

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

papillomas. In the same study, high doses of combined antioxidants, including caffeic acid, showed a significant decrease in growth of colon

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s in those same rats. No significant effect was noted otherwise. Caffeic acid is listed under some Hazard Data sheets as a potential carcinogen, as has been listed by the

International Agency for Research on Cancer The International Agency for Research on Cancer (IARC; french: Centre International de Recherche sur le Cancer, CIRC) is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and ...

as a Group 2B carcinogen ("possibly carcinogenic to humans"). More recent data show that

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

in the rats' guts may alter the formation of

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

s of caffeic acid. Other than caffeic acid being a

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...

antagonist (antithiamine factor), there have been no known ill effects of caffeic acid in humans. Also, caffeic acid treatment attenuated lipopolysaccharide (LPS)-induced sickness behaviour in experimental animals by decreasing both peripheral and central cytokine levels along with oxidative stress inflicted by LPS.

Chemistry

Caffeic acid is susceptible to

autoxidation Autoxidation (sometimes auto-oxidation) refers to oxidations brought about by reactions with oxygen at normal temperatures, without the intervention of flame or electric spark. The term is usually used to describe the gradual degradation of organic ...

. With transition metals, it forms transition metal-carboxylate complexes, but not salts.

Glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...

and

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

compounds (

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, some ...

, thioglycolic acid or thiocresol) or

ascorbic Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...

acid have a protective effect on browning and disappearance of caffeic acid. This browning is due to the conversion of ''o''-diphenols into reactive ''o''-quinones. Chemical oxidation of caffeic acid in acidic conditions using sodium periodate leads to the formation of dimers with a furan structure (isomers of 2,5-(3′,4′-dihydroxyphenyl)tetrahydrofuran 3,4-dicarboxylic acid). Caffeic acid can also be polymerized using the

horseradish peroxidase The enzyme horseradish peroxidase (HRP), found in the roots of horseradish, is used extensively in biochemistry applications. It is a metalloenzyme with many isoforms, of which the most studied type is C. It catalyzes the oxidation of various o ...

/ H₂O₂ oxidizing system.

Other uses

Caffeic acid may be the active ingredient in caffenol, a do-it-yourself black-and-white

photographic developer In the processing of photographic films, plates or papers, the photographic developer (or just developer) is one or more chemicals that convert the latent image to a visible image. Developing agents achieve this conversion by reducing the silve ...

made from

instant coffee Instant coffee is a beverage derived from brewed coffee beans that enables people to quickly prepare hot coffee by adding hot water or milk to coffee solids in powdered or crystallized form and stirring. Instant coffee solids (also called sol ...

. The developing chemistry is similar to that of

catechol Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is a toxic organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amoun ...

or pyrogallol. It is also used as a matrix in

MALDI In mass spectrometry, matrix-assisted laser desorption/ionization (MALDI) is an ionization technique that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. It has been applied to the analysis of b ...

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a '' mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is u ...

analyses.

Isomers

Isomers with the same molecular formula and in the hydroxycinammic acids family are: *

Umbellic acid Umbellic acid (2,4-dihydroxycinnamic acid) is a hydroxycinnamic acid. It is an isomer of caffeic acid. It is a precursor in the umbelliferone biosynthesis pathway. Umbelliferone is a phenylpropanoid and as such is synthesized from L-phenylalanin ...

(2,4-dihydroxycinnamic acid) * 2,3-Dihydroxycinnamic acid * 2,5-Dihydroxycinnamic acid

References

External links

* {{DEFAULTSORT:Caffeic Acid IARC Group 2B carcinogens Hydroxycinnamic acids Xanthine oxidase inhibitors Catechols Vinylogous carboxylic acids