Caffeic acid is a hydroxycinnamic acid

Hydroxycinnamic acid

Hydroxycinnamic acids are a class of polyphenols 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 are :* Alpha-cyano-4-hydroxycinnamic acid...

, a naturally occurring organic compound. This yellow solid consists of both phenol

Phenol

Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...

ic and acrylic

Acrylic acid

Acrylic acid is an organic compound with the formula CH2=CHCO2H. It is the simplest unsaturated carboxylic acid, consisting of a vinyl group connected directly to a carboxylic acid terminus. This colorless liquid has a characteristic acrid or tart smell. It is miscible with water, alcohols,...

 functional groups. It is found in all plants because it is a key intermediate in the biosynthesis

Biosynthesis

Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

 of lignin

Lignin

Lignin or lignen is a complex chemical compound most commonly derived from wood, and an integral part of the secondary cell walls of plants and some algae. The term was introduced in 1819 by de Candolle and is derived from the Latin word lignum, meaning wood...

, one of the principal sources of biomass

Biomass

Biomass, as a renewable energy source, is biological material from living, or recently living organisms. As an energy source, biomass can either be used directly, or converted into other energy products such as biofuel....

.

Occurrence and biological function

Caffeic acid, which is unrelated to caffeine

Caffeine

Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

, is biosynthesized by hydroxylation

Hydroxylation

Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...

 of coumaroyl

Coumaric acid

Coumaric acid is a hydroxycinnamic acid, an organic compound that is a hydroxy derivative of cinnamic acid. There are three isomers, o-coumaric acid, m-coumaric acid, and p-coumaric acid, that differ by the position of the hydroxy substitution of the phenyl group...

 ester of quinic ester. This hydroxylation produces the caffeic acid ester of shikimic acid

Shikimic acid

Shikimic acid, more commonly known as its anionic form shikimate, is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi , from which it was first isolated....

, which converts to chlorogenic acid

Chlorogenic acid

Chlorogenic acid is a hydroxycinnamic acid, a member of a family of naturally occurring organic compounds. These are esters of polyphenolic caffeic acid and cyclitol -quinic acid. It is an important biosynthetic intermediate. It also is one of the phenols found in coffee, bamboo Phyllostachys...

. It is the precursor to ferulic acid

Ferulic acid

Ferulic acid is a hydroxycinnamic acid, a type of organic compound. It is an abundant phenolic phytochemical found in plant cell wall components such as arabinoxylans as covalent side chains. It is related to trans-cinnamic acid. As a component of lignin, ferulic acid is a precursor in the...

, coniferyl alcohol

Coniferyl alcohol

Coniferyl alcohol is an organic compound. This colourless crystalline solid is a phytochemical, one of the monolignols. It is synthethized via the phenylpropanoid biochemical pathway. When copolymerized with related aromatic compounds, coniferyl alcohol forms lignin or lignans...

, and sinapyl alcohol

Sinapyl alcohol

Sinapyl alcohol is an organic compound derived from cinnamic acid. This phytochemical is one of the monolignols. It is biosynthetized via the phenylpropanoid biochemical pathway, its immediate precursor being sinapaldehyde. Sinapyl alcohol is a precursor to lignin or lignans. It is also a...

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

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 caffeic acid-O-methyltransferase.

Caffeic acid and its derivative caffeic acid phenethyl ester

Ester

Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

 (also known as CAPE, molecular formula : C₁₇H₁₆O₄,molar mass :284.30654 g/mol, exact mass : 284.104859) are produced in many kinds of plants.

In traditional and alternative medicine

Caffeic acid has been shown to inhibit carcinogenesis

Carcinogenesis

Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...

, although other experiments show possible carcinogenic effects. It is also known as an antioxidant

Antioxidant

An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

 in vitro

In vitro

In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

 and also in vivo

In vivo

In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

. Caffeic acid also shows immunomodulatory and antiinflammtory activity.

Caffeic acid outperformed the other antioxidants, reducing aflatoxin 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

Aspergillus flavus is a fungus. It is a common mold in the environment, and can cause storage problems in stored grains. It can also be a human pathogen, associated with aspergillosis of the lungs and sometimes causing corneal, otomycotic, and nasoorbital infections. Many strains produce...

aflatoxin production can be stymied by caffeic acid. This opens the door to using natural anti-fungicide

Fungicide

Fungicides are chemical compounds or biological organisms used to kill or inhibit fungi or fungal spores. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality and profit. Fungicides are used both in agriculture and to fight fungal infections in animals...

 methods by supplementing trees with antioxidants.

Oral

Mouth

The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....

 administration of high doses of caffeic acid in rats has caused stomach

Stomach

The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...

 papilloma

Papilloma

Papilloma refers to a benign epithelial tumor growing exophytically in finger-like fronds. In this context papilla refers to the projection created by the tumor, not a tumor on an already existing papilla . When used without context, it frequently refers to infections caused by human...

s, leading to the perception of caffeic acid as carcinogenic. In the same study, only high doses of combined antioxidants, including caffeic acid, showed a significant decrease in growth of colon

Colon (anatomy)

The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

 tumor

Tumor

A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

s in those same rats. No significant effect was noted otherwise.

Caffeic acid is still listed under older Hazard Data sheets as a potential carcinogen because of two early experiments on rats and mice. More recent data show that bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 in the rats' guts may alter the formation of metabolite

Metabolite

Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

s of caffeic acid. There have been no known ill-effects of caffeic acid in humans.

Caffeic acid and its derivative, Caffeic acid phenethyl ester (CAPE) have shown tumor-shrinking properties. When an anti-cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 drug

Drug

A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 was being sought, caffeic acid and CAPE were derived from Burning Bush

Euonymus alatus

Euonymus alatus, known variously as Winged Spindle, Winged Euonymus or Burning Bush, is a deciduous shrub native to eastern Asia, in central and northern China, Japan, and Korea. The shrub grows to 2.5 m tall , often wider than tall...

 (Euonymus alatus). "The subcutaneous and oral administrations of CA and CAPE significantly reduced liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 metastasis

Metastasis

Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. These results confirm the therapeutic

Pharmacotherapy

Pharmacotherapy is the treatment of disease through the administration of drugs. As such, it is considered part of the larger category of therapy....

 potential of the compounds and suggest that the anti-metastatic and anti-tumor effects of CA and CAPE are mediated through the selective suppression of MMP

Matrix metalloproteinase

Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....

-9 enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 activity and transcriptional

Transcription (genetics)

Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

 down-regulation

Regulation of gene expression

Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...

 by the dual inhibition of NF-κB as well as MMP-9 catalytic

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

 activity."
A study using the caffeic acid phenethyl ester (CAPE) showed a positive effect on reducing carcinogen

Carcinogen

A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...

ic incidence. Caffeic acid phenethyl ester

Ester

Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

 (CAPE) is an active component of propolis

Propolis

Propolis is a resinous mixture that honey bees collect from tree buds, sap flows, or other botanical sources. It is used as a sealant for unwanted open spaces in the hive. Propolis is used for small gaps , while larger spaces are usually filled with beeswax. Its color varies depending on its...

 from honeybee hives. It is known to have antimitogenic

Mitosis

Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

, anticarcinogenic, anti-inflammatory

Anti-inflammatory

Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....

, and immunomodulator

Immunomodulator

An immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...

y properties.

Another study also showed that CAPE suppresses acute immune and inflammatory

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 responses and holds promise for therapeutic uses to reduce inflammation.

This anti-inflammatory and anti-cancer property has also been shown to protect skin

Skin

-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

 cells when exposed to ultraviolet

Ultraviolet

Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...

 (UV) radiation

Radiation

In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...

, in particular UVC radiation and UVB radiation. This anti-cancer effect was also seen when mice skin was treated with bee propolis and exposed to TPA (a chemical) that induced skin papilloma

Papilloma

Papilloma refers to a benign epithelial tumor growing exophytically in finger-like fronds. In this context papilla refers to the projection created by the tumor, not a tumor on an already existing papilla . When used without context, it frequently refers to infections caused by human...

s. CAPE significantly reduced the number of papillomas.
Caffeic acid and chlorogenic acid from coffee beans both reduced DNA methylation

DNA methylation

DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...

 in vitro

In vitro

In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

 in two lines of human cancer cells. DNA methylation contributes to the growth of tumors and regulates the epigenetics

Epigenetics

In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...

 of cells that are passed along with DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 to future generations.

Caffeic acid has been shown to be an inhibitor of the lipoxygenase

Lipoxygenase

Lipoxygenases are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:...

 enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that forms leukotriene

Leukotriene

Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...

s from arachidonic acid

Arachidonic acid

Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...

. This function has been useful in scientific experiments to elucidate the roles of the leukotrienes in various inflammatory

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 responses.

Other uses

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

Photographic developer

In the processing of photographic films, plates or papers, the photographic developer is a chemical that makes the latent image on the film or print visible. It does this by reducing the silver halides that have been exposed to light to elemental silver in the gelatine matrix...

 made from instant coffee. The developing chemistry is similar to that of Catechol or Pyrogallol

Pyrogallol

Pyrogallol or benzene-1,2,3-triol is a benzenetriol. It is a white crystalline powder and a powerful reducing agent. It was first prepared by Scheele 1786 by heating gallic acid. An alternate preparation is heating para-chlorophenoldisulphonic acid with potassium hydroxide.When in alkaline...

.

It is also used as a matrix in MALDI

Matrix-assisted laser desorption/ionization

Matrix-assisted laser desorption/ionization is a soft ionization technique used in mass spectrometry, allowing the analysis of biomolecules and large organic molecules , which tend to be fragile and fragment when ionized by more conventional ionization methods...

 mass spectrometry

Mass spectrometry

Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...

analyses.