Surface psoralen

A few drugs depend for their therapeutic action upon light activation. Included in this review are dithranol, which has been suggested to exert its antipsoriatic action in this way, and the psoralens, which have long been used in combination with sunbathing to treat various skin conditions and now are also used against surface cancers. 

PUVA is most useful for the treatment of severe psoriasis. Early (patch and plaque) stage cutaneous T-cell lymphoma (CTCL) also responds to PUVA therapy. In addition, patients in advanced stages of CTCL have been treated with a modification of PUVA known as extracorporeal photopheresis. In this therapy, blood from a CTCL patient who has taken psoralen is exposed to UVA light and returned to the patient. Lymphocytes are altered or destroyed by the treatment, and theoretically, the return of these abnormal cells triggers an immune response directed against certain lymphocyte surface antigens. The effectiveness of this modality appears to be variable. 

Zobel, A.M. and Brown, S.A. (1 991) Psoralens on the surface of seeds of Rutaceae and fruits of Umbelliferae and Leguminosae. Canadian Journal of Botany 1 69, 485-488. 

Photophoresis is a variant of PUVA treatment (Edelson et al., 1987 Horio, 2000). Leukocytes from patients with cutaneous T-cell lymphoma or autoimmune disorders (rheumatoid arthritis and systemic sclerosis) are exposed to UVA radiation in the presence of a psoralen and given back to the patients. It is believed that PUVA changes some surface markers of T-cells and thus triggers the immune system. Thus, this treatment can be regarded as a beneficial application of a photoallergic reaction. 

In psoriasis, PUVA therapy (psoralen and UVA) leads to an inhibition of abnormally high rates of epidermal cell growth associated with the disease [297]. It has been shown that photoactivated psoralens are also potent inhibitors of epidermal cell growth in vitro. There are several lines of evidence that indicate the psoralen receptor is not associated with the DNA [298]. Studies on the distribution of compounds in cells based on their fluorescence properties demonstrated that psoralen (2) was present in the cytoplasm and cell surface membranes [299]. When cell membrane Auction of HeLa cells were prepared, psoralen receptor binding could be detected [297]. Using [3H]-8-MOP (methoxypsoralen), the cellular distribution of covalently bound psoralen in HeLa cells was also examined [300]. In these experiments, cells were treated with [3H]-8-MOP, then pulsed with UV light. It was indicated that labeled 8-MOP was distributed in cytoplasm and membrane finctions. These results have been repeated in several laboratories and all of them implicate targets outside of the nucleus... 

Zobel, A.M., and S. A. Brown. 1991. Dermatitis-inducing psoralens on the surfaces of seven medicinal plant species. J. Toxicol. Cutan. Ocular Toxicol. 10(3) 223-231. 

The interaction of MNPs with DNA is a well-known phenomenon [86-89], and single- or double-strand DNA is decorated by MNPs, which can easily be imaged by transmission electron microscopy (TEM) or AFM [90-92]. Various surface-functionalized AuNPs have been prepared to attach AuNPs securely to DNA molecules. In numerous studies, such AuNPs were prepared by surface modifications with cationic thiols [54, 55, 92] or intercalators [93, 94]. The ID chains of AuNPs coated with cationic trimethyl(mercaptoundecyl) ammonium monolayers were electrostatically assembled along DNA molecules in solution by the relative molar quantities of AuNPs and DNA base pairs. Since psoralen acts as a specific intercalator for A-T base pairs, the functionalized AuNPs were assembled onto the pA-pT ds-DNA [93]. Furthermore, UV irradiations induced the reaction between the psoralen units and the thymine of DNA, and then covalently fixed AuNPs to the DNA. 

Hydrodiffusion is a steam distillation method, whereby steam is fed to the plant material from the top. Steam penetrating the plant matrix condenses and forces the essential oil to diffuse to the surface. Because of gravity, oil leaves the vessel together with the condensate water from the bottom of the still. Powdering the material results in better oil yields. This technique is suitable both for superficial and subcutaneous oils. The disadvantage of this technique is the undesired extraction of coumarins, psoralens, and chlorophyll into the oil. Therefore, hydrodiffusion has not become a widely used distillation technique. 

The most stable complex has the ligand perfectly intercalated between T and A, interacting only with those base pairs. During theMDsimulation the psoralen was however rotated 90 degrees from the initial pose to the final one, as is shown in Figure 3. In addition, the van der Waals surface is closed around the ligand... 

Figure 2 (a) Space-filling model of psoralen interacting with DNA bases for orientation 3 inserted between GC. (b) van derWaals contact surface between liquid and DNA. 

PUVA therapy consists of the patient receiving total body irradiation with ultraviolet A (UVA) light several times a week after taking a psoralen. Most commonly available psoralens for photochemotherapy include 8-methoxypsoralen or 8-MOP (also called methoxsalen or xanthotoxin), 5-methoxypsoralen or 5-MOP (or bergapten), angelicin, 4,5 -dimethylangelicin, and 4,5, 8-trimethoxypsoralen or 4,5, 8-trimethoxypsoralen (TMP) [104]. Psoralen is taken 2 h before irradiation and can be administered orally (5-MOP or 8-MOP) or topically, either painted onto the skin surface or, more frequently, using a bath delivery system... 

Decreased epidermal proliferation is considered to be the main mechanism of action of PUVA in the treatment of psoriasis. Once excited by UVA, psoralens can react with molecular oxygen, producing reactive oxygen species that cause mitochondrial dysfunction and lead to apoptosis of skin Langerhans cells, keratinocytes, and lymphocytes [134]. PUVA further decreases epidermal cell proliferation by noncompetitively binding to epidermal growth factor receptors and directly altering the cell surface membrane. 

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