Objective(s): To observe and determine the effect and mechanism of psoralen on tumor necrosis factor-α (TNF-α )-induced muscle atrophy. Materials and Methods: Three sets of C2C12 cells, including blank control, TNF-α (10 or 20 ng/ml) treatment and a TNF-α (10 or 20 ng/ml) plus psoralen (80 μ M) administration were investigated. Cell viability was assessed using Cell Counting Kit-8 (CCK-8) assay. Western blot analysis was used to detect protein expression of atrophic markers. Flowcytometry was used to observe the effect of psoralen on apoptosis. A quantitative real-time PCR (qRT-PCR) assay was performed to detect the mRNA level of miR-675-5P. Results: TNF-α (1, 10, 20 and 100 ng/ml) treatment inhibited C2C12 myoblast viability (P<0. 001), while 24 hr of psoralen administration increased the viability, and lowered TNF-α cytotoxicity (P<0. 001). MURF1, MAFbx, TRIM62 and GDF15 expressions were significantly increased in TNF-α (10 ng/ml or 20 ng/ml)-treated group (P<0. 001), and psoralen could significantly decrease the expression of these proteins (P<0. 001). Apoptotic rate of C2C12 myoblasts was increased after TNF-α (10 ng/ml and 20 ng/ml) treatment, and was significantly decreased after psoralen treatment (P<0. 001). miR-675-5P was increased in TNF-α-treated C2C12 myoblasts compared to control group, and it was significantly decreased after psoralen treatment. Conclusion: Psoralen could reduce TNF-α-induced cytotoxicity, atrophy and apoptosis in C2C12 myoblasts. The therapeutic effect of psoralen may be achieved by down-regulating miR-675-5P.

Introduction: Psoralens are photoactived naturally occurring plant biosynthetic metabolites. These compounds are widely used in the treatment of proliferate disorders and have been shown to be mutagenetic and carcinogenetic. The present study was done to investigate the effects of methoxsalen on the levels of sex hormones in the mice.Materials and Methods: For this experiment, the female mice were divided into three groups. Control (no injection), Sham (corn oil injection) and methoxsalen group (60 mg/kg i.p, consecutive doses for 15 days). Animals were killed at proestrus phase. Blood samples were collected and estrogen, LH and FSH levels were analyzed by radioimmunoassay. Data were analyzed using oneway ANOVA. Significance was set at p<0.05.Results: The observed level of estrogen was significantly decreased. There was a significant increase in LH and FSH levels as compared with control group.Conclusion: According to the results, it could be suggested that the consecutive dose of methoxsalen can exert significant effects on female mice. On the other hand, hormonal variations following short term methoxsalen administration may be responsible for changes in infertility pattern in mice.

Psoralen is one of the important secondary metabolites in Psoralea corylifolia. The important aspect of medicinal value of psoralen can be indicated to anticancer activity against leukemia, lung and breast cancers. In this research due to the pharmaceutical importance of psoralen, pathway of psoralen synthesis was studied. For the first time we isolate and characterized the gene coding psoralen key enzyme from the leaves of the Psoralea corylifolia by the different molecular techniques. Result of molecular analysis revealed that the length of this gene was 1237 bp. Also, the sequence analysis of nucleotides by using available bioinformatics data in NCBI found that psoralen synthase gene has 93% similarity with this gene in Ammi magus.

Background and Objective - Punch grafting is a therapy for vitiligo but, to our knowledge, its combination with outdoor topical psoralen plus ultraviolet A radiation (PUVA) has not yet been studied. This study was designed to evaluate the efficacy of combination of punch graft and outdoor topical PUVA in recalcitrant vitiligo. Methods - The study was performed in Razi Hospital, Tehran in 2000. After obtaining informed consent, 20 patients with stable and refractory vitiligo (4 segmental, 8 focal and 8 generalized) underwent treatment with punch grafting. After 3 months, outdoor topical PUVA with 8-methoxypsoralen was instituted and continued for a maximum of 4 months. Results - After the 3 months of punch grafting, only nine patients experienced 33 - 66% repigmentation. Four months after starting topical outdoor PUVA, 13 patients experienced 90 - 100% and three patients 25 - 50% repigmentation. One focal and three generalized patients showed no response. Conclusion - The combination of punch grafting and topical PUVA may be an effective treatment in stable and intractable vitiligo, especially the segmental and localized types.

Background: Topical corticosteroids and oral psoralen plus ultraviolet A radiation (PUVA therapy) are two common treatment methods for vitiligo. The aim of this study was to compare the efficacy, complications and patterns of repigmentation of these two methods.Methods: This prospective randomized clinical trial was conducted from July 2007 to October 2008. Patients with disseminated vitiligo were divided into two groups. PUVA therapy was administered in one group and topical clobetasol was used in the other group.Results were recorded in 4 categories and therapeutic findings and complications were compared after 24 weeks.Results: Among 37 participants in the PUVA therapy group, 18 (48.6%) patients achieved marked and 14 (37.8%) patients showed good repigmentation. Similarly, among 35 participants in the clobetasol group, 6 (17.1%) patients showed marked and 8 (22.8%) patients showed good repigmentation. treatment complications were observed in 16.2% of the participants in PUVA group and 28.6% of the participants in clobetasol group. The patterns of repigmentation were different in the two groups.Conclusion: PUVA showed better therapeutic effects, and did not cause significant complications. Therefore, it could be used as one of the first line medications in the treatment of vitiligo.

Chronic graft versus host disease (GVHD) remains the most common late complication of allogenic stem cell transplantation and the most frequent cause of morbidity and mortality in these patients. To control this condition, ImmunosuppreSlve drugs are usually administered at a high dose and for a long time, which may result in several side effects. Five clinically and patients with histopathologically established cGVHD (3 lichenoid, 1 sclerodermoid and 1 mixed lichenoid-sclerodermoid) , who failed to respond to conventional immunosuppressive therapy were treated with psoralen and UVA (PUVA). Treatment was administered in a standard protocol three times a week on nonconsecutive days and were continued at least for 12 weeks. All 3 lichenoid cases showed complete improvement. In the sclerodermoid case there was partial response and in the mixed type case the partial response of sclerodermoid lesion and complete response of lichenoid lesions were observed. With the exception of a slight increase in liver tranferases, no other adverse reactions occurred. In conclusion, PUVA can be a safe and effective therapy in conjunction with systemic agents for chronic GVHD especially in lichenoid form.

Background: Chronic graft versus host disease (ch.GVHD) is the most frequent late complication after allogenic stem-cell transplantation. Systemic immunosuppressive agents are usually required to control the disease. Psoralen plus UVA (PUVA) has been used for the treatment of ch.GVHD with variable beneficial effects. The objective of this study was to assess the efficacy and safety of a relatively lower dose of oral psoralen compared with previous reports, for the treatment of ch.GVHD patients with PUVA.Methods: Eleven patients who received allogenic bone marrow transplantation and had severe progressive ch.GVHD that was unresponsive to conventional immunosuppressive treatments were treated with oral 8-methoxypsoralen (0.2 mg/kg, up to 10 mg) two hours before exposure to UVA.Results: The patients received a median of 43 treatments (range: 18 to 72). Mean cumulative dose of UVA was 200.5 J/cm2 (range, 116.5-306.5 J/cm2). In four of the 11 patients, there was a complete resolution of cutaneous ch.GVHD and the remaining seven patients achieved partial response with PUVA treatment. Complete and partial remission was observed in four and six patients with lichenoid lesions, respectively, but all of the four patients with sclerodermoid GVHD showed partial response to PUVA treatment. We observed no side effects like phototoxicity, nausea and vomiting, and exacerbation of GVHD. Liver enzymes raised in five patients, causing no significant morbidity for them. Conclusion: Low-dose psoralen plus UVA can be a safe and effective therapy for chronic cutaneous GVHD. Although the number of treatments and total cumulative exposure to UVA was rather high in our study, we observed no phototoxic reaction or severe irreversible liver damage due to phototherapy, which may be because of a relatively lower dose of methoxsalen used in our patients. Psoralen plus UVA is effective particularly in lichenoid GVHD lesions but sclerodermoid lesions may also benefit from this therapy.