The furanocoumarins, or furocoumarins, are a class of organic chemical compounds produced by a variety of plants. Most of the plant species found to contain furanocoumarins belong to a handful of plant families. The families

Apiaceae Apiaceae or Umbelliferae is a family of mostly aromatic flowering plants named after the type genus '' Apium'' and commonly known as the celery, carrot or parsley family, or simply as umbellifers. It is the 16th-largest family of flowering plan ...

and

Rutaceae The Rutaceae is a family, commonly known as the rueRUTACEAE
in BoDD – Botanical Der ...

include the largest numbers of plant species that contain furanocoumarins. The families

Moraceae The Moraceae — often called the mulberry family or fig family — are a family of flowering plants comprising about 38 genera and over 1100 species. Most are widespread in tropical and subtropical regions, less so in temperate climates; however ...

and

Fabaceae The Fabaceae or Leguminosae,International Code of Nomenc ...

include a few widely distributed plant species that contain furanocoumarins. Generally furanocoumarins are most abundant in plants that have flowered and in ripe seeds and fruits. (An exception is the

common fig The fig is the edible fruit of ''Ficus carica'', a species of small tree in the flowering plant family Moraceae. Native to the Mediterranean and western Asia, it has been cultivated since ancient times and is now widely grown throughout the worl ...

where furanocoumarins are found chiefly in the milky sap of the leaves and shoots but not the fruits. Cited in McGovern and Barkley 2000, section&nbs
Phytophotodermatitis
) During the early stages of plant growth, their presence is not easily detected.

Structure

The chemical structure of furanocoumarins consists of a

furan Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans. Furan is a colorless, flammable, highl ...

ring fused with a coumarin. The furan ring may be fused in various ways producing several different

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...

s. The parent compounds of the most common isomers are

psoralen Psoralen (also called psoralene) is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered ...

and

angelicin Angelicin is the parent compound in a family of naturally occurring organic compounds known as the angular furanocoumarins. Structurally, it can be considered as benzapyra-2-one fused with a furan moiety in the 7,8-position. Angelicin is commonly ...

. Derivatives of these two compounds are referred to respectively as linear and angular furanocoumarins, so called since they exhibit a linear or angular chemical structure.

Biosynthesis

The compounds are biosynthesized partly through the

phenylpropanoid pathway The phenylpropanoids are a diverse family of organic compounds that are synthesized by plants from the amino acids phenylalanine and tyrosine. Their name is derived from the six-carbon, aromatic phenyl group and the three-carbon propene tail of ...

and the

mevalonate pathway The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl ...

, which is biosynthesized by a coupling of

dimethylallyl pyrophosphate Dimethylallyl pyrophosphate (DMAPP; or alternatively, dimethylallyl diphosphate (DMADP); also isoprenyl pyrophosphate) is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynt ...

(DMAPP) and

7-hydroxycoumarin Umbelliferone, also known as 7-hydroxycoumarin, hydrangine, skimmetine, and ''beta''-umbelliferone, is a natural product of the coumarin family. It absorbs ultraviolet light strongly at several wavelengths. There are some indications that this c ...

(umbelliferone).

Effects

Direct toxicity

Many furanocoumarin compounds are toxic. The

phytochemical Phytochemicals are chemical compounds produced by plants, generally to help them resist fungi, bacteria and plant virus infections, and also consumption by insects and other animals. The name comes . Some phytochemicals have been used as poison ...

s enter the nucleus of

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

cells and form a bond (crosslinking) with the DNA when exposed to UV, which causes cell death and causes

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

via activation of the arachidonic acid cascade. The result is known as phytophotodermatitis, a serious skin inflammation. Furanocoumarins produced by plants may serve as a defense mechanism against predators such as

insect Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three pa ...

s and

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...

s. It is also likely that furanocoumarins are related to a plant's natural defense against fungal attack. In particular, the linear furanocoumarins (

bergapten Bergapten (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot family Apiaceae and the citrus family Rutaceae. For example, bergapten has been extracted from 24 ...

, and

methoxsalen Methoxsalen, sold under the brand name Oxsoralen among others, is a medication used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas in conjunction with exposing the skin to ultraviolet (UVA) light from lamps or sunlight. Met ...

), which occur naturally in

Rutaceae The Rutaceae is a family, commonly known as the rueRUTACEAE
in BoDD – Botanical Der ...

, and other plant families, are known to be toxic to fungi. Plants that cause phytophotodermatitis usually contain linear furanocoumarins. Furanocoumarins are found in the sap of plants such as ''

Ammi majus ''Ammi majus'', commonly called bishop's flower, false bishop's weed, laceflower, bullwort, etc., is a member of the carrot family Apiaceae. The plant, which has white lace-like flower clusters, has a large distribution through Southern Europe ...

'',

parsnip The parsnip ('' Pastinaca sativa'') is a root vegetable closely related to carrot and parsley, all belonging to the flowering plant family Apiaceae. It is a biennial plant usually grown as an annual. Its long taproot has cream-colored skin an ...

, and

giant hogweed ''Heracleum mantegazzianum'', commonly known as giant hogweed, is a monocarpic perennial herbaceous plant in the carrot family Apiaceae. ''H. mantegazzianum'' is also known as cartwheel-flower, giant cow parsley, giant cow parsnip, or hogsb ...

. At least 36 species of the genus '' Heracleum'' in the family

are known to contain one or more furanocoumarin compounds.

Medication interactions

Furanocoumarins have other biological effects as well. For example, in humans,

bergamottin Bergamottin (5-geranoxypsoralen) is a natural furanocoumarin found in the pulp of pomelos and grapefruits. It is also found in the peel and pulp of the bergamot orange, from which it was first isolated and from which its name is derived. Chemis ...

and

6',7'-dihydroxybergamottin 6',7'-Dihydroxybergamottin is a natural furanocoumarin found in pomelos, grapefruits, and sour oranges, in both the peel and the pulp. Along with the chemically related compound bergamottin, it is believed to be responsible for a number of grapefr ...

are responsible for the " grapefruit juice effect", in which these furanocoumarins affect certain P450 liver and gut enzymes, such as the inhibition of

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...

which either activates or deactivates many drugs, thus leading to ''higher'' or ''lower'' levels in the bloodstream. Furanocoumarins have various effects which can specifically ''increase'' or ''decrease'' (depending on the drug) the blood levels of many pharmaceuticals in ways that can be life-threatening, so FDA-approved drugs include warnings for grapefruit.

References