Skin pigmentation psoralen

Many natural products contain the coumarin structure [28]. Aesculetin 15 is extracted from horse chestnuts and psoralen 16 from the Indian plant Psoralea corylifolia. Furocoumarins such as 16 are photochemically active. On UV irradiation, they induce processes in the cell which lead to an increase in skin pigmentation and inhibition of cell division. This is due to the formation of cyclobutane with the pyrimidine bases of nucleic acids. Psoralens are used in the treatment of psoriasis. 

Psoralen, bergapten (D 22.2.2) Compounds enhancing skin pigmentation... 

Psoralens have a toxic effect on the skin, which manifests itself in the summer as phytophotodermatitis. It results from contact with certain plants or herbs that contain psoralens and then from exposure to sunlight. However, it was also recognized that this may be a beneficial effect that, because it allows modulation of skin pigmentation, can be used for medicinal purposes or in cosmetics. - ... 

Methoxy-psoralcn (Methox-salen) 1947-1960 Treatment of vitiligo by oral (10-20 mg) and topical 8-MOP(l%) Increased skin pigmentation with sun + 8-MOP (1955). Increased sun tolerance (1959). Relation of structure and photoactivity of psoralens (1956-1960). Synthesis of psoralens (1956-1960). Lethal effect on bacteria, fungi in vitro (1958). Action spectra 340-360 nm. in vitro and in vivo (1959-1960). 

Vitiligo No safe and relfable treatment. Methoxsalen or other psoralen. Topically or syscemically, plus daily exposure to UVA (PUVA) is toxic, and ineffective in Caucasians. Sunscreens to protect the depigmented areas and reduce pigmentation of surrounding skin. Probably an autoimmune disease Note dose-dependent risk of squamous cell cancer with PUVA... 

Toxicological Implications for Man. Because psoralens are potent photoactive compounds, they have been used medically for treatment of skin de pigment at ion or vitiligo (16,17), and psoriasis (18). However, there has recently been concern associated with the medical use of these compounds (19). This concern is due to the observed phototoxicity during therapeutic use (17), the suspected photocarcinogenicity of xanthotoxin (20,21), and the latent onset of tumors in treated laboratory animals (22). Acute gout secondary to psoriasis also was exacerbated by psoralen and UV-A (PUVA) photochemotherapy (23). 

Some adverse effects of the various psoralens have been reported. Re-pigmentation of the skin brought about by psoralen is found to be unreliable [567] maybe the cause of this failure is the absence of melanocytes in pathological conditions of the skin [545, 546]. 

Poison-ivy-like streaks of vesicles and bullae in light-exposed sites can be caused by photocontact dermatitis, and when produced by psoralens, the acute eruption is typically followed by pigmentation There are multiple mechanisms of phytophotodermatitis, but most such reactions are caused by plants containing furanocoumarins or psoralens, including certain members of the Umbelliferae and Rutaceae (citrus) [125]. The sensitizer can be spread with the hands or even thrown onto the skin from a string trimmer [126]. Of course, it is necessary to have adequate UV-A exposure in addition to contact with the plant. 

The main psoralen photosensitizing effect used in the treatment of certain skin diseases involves stimulating the pigmentation of melanocytes, increasing melanin synthesis on one hand and antiproliferative activity of psoriatic plaques on the other. The effects may, therefore, appear to be contradictory. However, recent findings explain that the two activities are likely to be connected to distinct cellular targets that are photomodified by psoralens in different ways. 

Besides their application in PUVA therapy to treat diseases characterized by hyperproliferation or the lack of pigmenting ability of some regions of the skin, in the last years, psoralens were also used in photopheresis, a therapeutic approach useful in treating immune disorders. 

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