Thefuranocoumarins, orfurocoumarins, are a class oforganic 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 familiesApiaceae andRutaceae (citrus family) include the largest numbers of plant species that contain furanocoumarins.[1] The familiesMoraceae andFabaceae include a few widely distributed plant species that contain furanocoumarins.[2]
Generally, furanocoumarins are most abundant in plants that have flowered and in ripe seeds and fruits.[2] (An exception is thecommon fig where furanocoumarins are found chiefly in the milky sap of the leaves and shoots but not the fruits.[3]) During the early stages of plant growth, their presence is not easily detected.
The chemical structure of furanocoumarins consists of afuran ring fused with acoumarin. The furan ring may be fused in various ways, producing several differentisomers. The parent compounds of the most common isomers arepsoralen andangelicin. Derivatives of these two compounds are referred to respectively as linear and angular furanocoumarins,[4] so called since they exhibit a linear or angular chemical structure.
The compounds are biosynthesized partly through thephenylpropanoid pathway and themevalonate pathway, which is biosynthesized by a coupling ofdimethylallyl pyrophosphate (DMAPP) and7-hydroxycoumarin (umbelliferone).
Many furanocoumarin compounds are toxic. Thephytochemicals enter the nucleus ofepithelial cells and form a bond (cross-linking) with theDNA when exposed to UV, which causes cell death and causesinflammation via activation of thearachidonic acid cascade. The result is known asphytophotodermatitis, a serious skin inflammation.[5]
Furanocoumarins produced by plants may serve as adefense mechanism against predators such asinsects andmammals.[6][7] It is also likely that furanocoumarins are related to a plant's natural defense againstfungal attack.[8] In particular, the linear furanocoumarins (psoralen,bergapten, andmethoxsalen), which occur naturally inApiaceae,Rutaceae, and other plant families, are known to be toxic to fungi.[9] Plants that cause phytophotodermatitis usually contain linear furanocoumarins.[8]
Furanocoumarins are found in the sap of plants such asAmmi majus,parsnip, andgiant hogweed. At least 36 species of the genusHeracleum in the familyApiaceae are known to contain one or more furanocoumarin compounds.[10]
Thetoxin can sometimes be found even in the most common foods, includingcarrots,parsley,limes, andlemons, as reported in theNew England Journal of Medicine in the case of a man who manually squeezed a dozen limes and then inadvertently exposed his hand directly to the sunlight without precaution, triggering a severe phytophotodermatitis for several months.[11] The identified culprit was the prolonged exposure of both his hands to lime juice followed by that of sunlight UV.[11]
Furanocoumarins have other biological effects as well. For example, in humans,bergamottin and6',7'-dihydroxybergamottin are responsible for the "grapefruit juice effect", in which these furanocoumarins affect certainP450 liver and gut enzymes, such as the inhibition ofCYP3A4 which either activates or deactivates many drugs, thus leading tohigher orlower levels in the bloodstream.[12] Furanocoumarins have various effects which can specificallyincrease ordecrease (depending on the drug) the blood levels of many pharmaceuticals in ways that can be life-threatening, soFDA-approved drugs include warnings for grapefruit.
