Caffeic acid is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the formula . It is a polyphenol with a key role in scavenging

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS) generated in energy metabolism. Caffeic acid is also one major polyphenol responsible for maintaining normal levels of

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

(NO) within cells. Caffeic acid is a yellow, solid chemical compound that is structually 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 List of phytochemicals in food, phytochemicals tha ...

, and the molecule consists of both phenolic and acrylic functional groups. Caffeic acid is found in all plants as an intermediate in the

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

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 rigidit ...

, a naturally occurring complex

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

representing the principal components of

biomass Biomass is a term used in several contexts: in the context of ecology it means living organisms, and in the context of bioenergy it means matter from recently living (but now dead) organisms. In the latter context, there are variations in how ...

and its residues. It is chemically unrelated to

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

; instead, the shared name is related to its presence in

coffee Coffee is a beverage brewed from roasted, ground coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content, but decaffeinated coffee is also commercially a ...

Natural occurrences

Caffeic acid can be found in the bark of ''

Eucalyptus globulus ''Eucalyptus globulus'', commonly known as southern blue gum or blue gum, is a species of flowering plant in the family Myrtaceae. It is a tall, evergreen tree Endemism, endemic to southeastern Australia. This ''Eucalyptus'' species has most ...

'' the

barley Barley (), a member of the grass family, is a major cereal grain grown in temperate climates globally. It was one of the first cultivated grains; it was domesticated in the Fertile Crescent around 9000 BC, giving it nonshattering spikele ...

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''.

Occurrences in food

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

at 63.1-96.0 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 a culinary herb consisting of the dried aerial parts of some members of the genus ''Thymus (plant), Thymus'' of flowering plants in the mint family Lamiaceae. Thymes are native to Eurasia and north Africa. Thymes have culinary, medici ...

, sage and

spearmint Spearmint (''Mentha spicata''), also known as garden mint, common mint, lamb mint and mackerel mint, is native to Europe and southern temperate Asia, extending from Ireland in the west to southern China in the east. It is naturalized in many othe ...

(at about 20 mg per 100 g), and in spices, such as Ceylon cinnamon and

star anise ''Illicium verum'' (star anise or badian, Chinese star anise, star anise seed, star aniseed and star of anise) is a medium-sized evergreen tree native to South China and northeast Vietnam. Its star-shaped pericarps harvested just before ripen ...

(at about 22 mg per 100 g). Caffeic acid occurs at moderate levels in sunflower seeds (8 mg per 100 g), apple sauce,

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 also ...

s and prunes (at about 1 mg per 100 g). It occurs at remarkably high levels in black chokeberry (141 mg per 100 g). It is also quite high in the South American herb

yerba mate Yerba mate or yerba maté (), ''Ilex paraguariensis'', is a plant species of the holly genus native to South America. It was named by the French botanist Augustin Saint-Hilaire. The leaves of the plant can be steeped in hot water to make a bev ...

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

and rye.

Biosynthesis

Caffeic acid is biosynthesized by hydroxylation of coumaroyl ester of quinic acid (esterified through a side chain alcohol). This hydroxylation produces the caffeic acid ester of shikimic acid, which converts to chlorogenic acid. It is the precursor to ferulic acid, coniferyl alcohol, and sinapyl alcohol, all of which are significant building blocks in lignin. The transformation to ferulic acid is catalyzed by the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

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 ferulic acid. 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. Caffeic acid is susceptible to autoxidation. Glutathione and thiol compounds (

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

, thioglycolic acid or thiocresol) or ascorbic 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/ H₂O₂ oxidizing system.

Glycosides

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

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

'' fruits).

Pharmacology

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

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

'' 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 ...

cell line has recently been established. Caffeic acid is an

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

''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, an ...

''. Caffeic acid also shows immunomodulatory and

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

activity. Caffeic acid outperformed the other antioxidants, reducing

aflatoxin Aflatoxins are various toxicity, poisonous carcinogens and mutagens that are produced by certain Mold (fungus), molds, especially ''Aspergillus'' species such as ''Aspergillus flavus'' and ''Aspergillus parasiticus''. According to the USDA, "The ...

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 pesticides used to kill parasitic fungi or their spores. Fungi can cause serious damage in agriculture, resulting in losses of yield and quality. Fungicides are used both in agriculture and to fight fungal infections in animals, ...

by supplementing trees with antioxidants. Studies of the

carcinogenicity A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and Biological agent, biologic agent ...

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 cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...

, 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 upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

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; ) is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and coordinate research into the causes of cancer. It also cance ...

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

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

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, c ...

s of caffeic acid. Other than caffeic acid being a

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin – an Nutrient#Micronutrients, essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosp ...

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 Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

levels along with oxidative stress inflicted by LPS.

Other uses

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

photographic developer In the Photographic processing, 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 conversio ...

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. The product was first invented in Inver ...

. The developing chemistry is similar to that of catechol or

pyrogallol Pyrogallol is an organic compound with the formula C6H3(OH)3. It is a water-soluble, white solid although samples are typically brownish because of its sensitivity toward oxygen. It is one of three isomers of benzenetriols. Production and reac ...

. It is also used as a matrix in MALDI

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 used ...

analyses.

Isomers

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