Photosensitization furanocoumarins

Other coumarin-related compounds include furans, found in moldy sweet potatoes, and the furan coumarin complexes (furanocoumarins) found in parsnip leaves (psoralens). They are photoreactive compounds (primary photosensitizers) that exacerbate sunburn to psoralen exposed skin. 

Recognition of the photosensitizing effect of the naturally occurring furanocoumarin psoralin (desmethoxy (3-6)) led to trials of its utility for the treatment of skin diseases such as psoriasis. The partial effectiveness of this compound led to the preparation of synthetic analogues. The two commercially available drugs, methoxsalen (3-8) and trioxsalen (4-6), are used in a procedure that goes by the acronym PUVA (psoralen and UVA irradiation) for the treatment of psoriasis and other skin diseases. 

Linear furanocoumarins are polenl photosensitizing agents in celery, parsley, parsnips, limes, and figs. The most commonly reported symptoms include contact dermatitis and photodermatitis. particularly on the hands and forearms. 

Furanocoumarins are photosensitizing agents used in the treatment of pigment disorders. Ayurveda, the aneient scienee of India, has described the use of bawachi (Psoralia corylifolia) for the treatment of leucoderma. Psoralens isolated from the medicinal herb, are reputed drugs in the field of dermatology. 

As well as these beneficial (either for the plant or for humankind) uses of photoactivation of plant compounds, there are equally numerous and varied examples of harmful phototoxic responses to plant compounds. Many plants potentially ingested by livestock can initiate photosensitizing responses [38]. In particular, plants that produce sufficient concentrations of furanocoumarins, hypericin, and cercosporin have been documented to affect livestock in this manner [39]. A specific example of non-target species photosensitization by plant compounds is the dramatic erythemic response of agricultural workers exposed to the sap of celery (Apium graveolens) plants during harvest [40]. 

Furanocoumarins also have photosensitizing effect on dermatophytes [132]. Xanthotoxin (36) showed activity in darkness against Candida albicans and Cryptococcus laurentii [133]. 

Fig. (1). The pyramid of relative skin photosensitizing activity among several psoralens. The furanocoumarins at the bottom are almost inactive.

The furanocoumarins, psoralen, bergapten, xanthotoxin and isopimpinellin, were detected in celery leaves and stalk. The total furanocoumarin content ranged from about 12 to 50 mg/kg in Florida cultivars [54]. Treatment with fungicides increased the bergapten content 2-4 times in leaves and stalk, xanthotoxin 2-3 times in stalk, and isopimpinellin about 2-3 times in leaves, while psoralen levels remained constant. This fact is of some importance since linear furanocoumarins are the cause of photosensitive reactions in humans. 

Although furanocoumarin compounds, such as those present in angelica or purple angelica, have photosensitizing... 

Although furanocoumarins, compounds that can cause photosensitivity after contact with skin, have been identified in glehnia (Mizukami et al. 1993), no cases of photosensitivity have been reported. 

HPLC analysis was performed on the extracts of the Moraceae, and a number of furanocoumarins were identified including psoralen (1) and S-methoxypsoralen (II) (5-MOP). Furanocoumarins are potent photosensitizers and their presence in a small number of Ficus species has already been reported (46-47). Table IB lists the distribution of furanocoumarins in Ficus. One important point that should be noted is the limited number of Ficus species from which furanocoumarins have been identified. The actual number of Ficus species tested for these compounds is unknown, but furanocoumarins have been detected in only seven species from a genus with roughly 1000 members. 

The furanocoumarin derivative, 5-methoxypsoralen, and other related compounds, are responsible for the phototoxicity of various essential oils on skin (9, 65, 169). Other studies with lapachol concern its toxicity to viruses (98) and parasites (102). The sensitizing capacity of naphthoquinones was studied on guinea pigs (166). The problem of photosensitization was present in livestock (93). The effects were caused by 5-methoxypsoralen, and also the bis-anthraquinone hypericin. The flavanoids are thought to be responsible for a contact eczema from Robinia sp. (190). 

The cutaneous phototoxicity of a-terthienyl was studied in guinea pig skin, both in vitro and in vivo 203). Effective penetration through the epidermis and superficial dermis produced cutaneous photosensitization comparable to that of intradermally administered a-terthienyl. Phototoxicity was accompanied by a corresponding inhibition of epidermal DNA synthesis in normal and hyperproliferative skin. The authors suggested that a-terthienyl might provide a selective and safer alternative to coal tar and furanocoumarin derivatives for the treatment of psoriasis and other cutaneous diseases by photosensitization. However, no clinical studies in this direction have yet been published. 

Ashwood-Smith, M.J., G.A. Poulton, O. Ceska, M. Liu, and E. Furniss An ultrasensitive Bioassay for the Detection of Furanocoumarins and Other Photosensitizing Molecules. Photochem. Photobiol. 38, 113 (1983). 

---