Hypertrophic Lichen Planus in a 38-year-old Filipino male: A case report

@#Hypertrophic lichen planus (HLP) is a papulosquamous eruption presenting with extremely pruritic hyperkeratotic flat-topped papules, plaques, and nodules. This is a case of 38-year-old male who presented with a 2-month history of generalized erythematous-to-hyperpigmented papules, patches, and plaques topped with white-to-gray oyster shell-like scales on a background of hyperpigmented macules and patches. There was no involvement of the conjunctival, otic, oral, and genital mucosae, and palmar and plantar aspects of the hands and feet. Dermoscopy showed reticular pearly white structures corresponding to the Wickham striae, comedo-like openings, blue-gray dots, brownish-black dots, and scales. Histopathologic examination revealed marked compact hyperkeratosis, wedge-shaped hypergranulosis, irregular saw-toothed epidermal acanthosis, scattered dyskeratotic keratinocytes, and superficial perivascular lichenoid infiltrate of lymphocytes, histiocytes, and melanophages. The patient was managed as a case of HLP. He was started on methotrexate 10 mg per week, bath psoralen photochemotherapy (PUVA) three times a week, betamethasone valerate 1mg/g cream twice a day for 2 weeks alternating with tacrolimus 0.1% ointment twice a day for another 2 weeks, 10% lactic acid, emollients, and sunscreen. After 6 months of treatment, there was almost 80% improvement of lesions and relief of pruritus.

Protective effects of psoralen polymer lipid nanoparticles on doxorubicin - induced myocardial toxicity

Abstract Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.

Ameliorative effect of psoralen on acute liver injury induced by carbon tetrachloride in mice / 中国药科大学学报

@#To investigate the ameliorative effect of psoralen (PSO) on carbon tetrachloride (CCl4)-induced acute liver injury in mice and its potential mechanism, female C57BL/6J mice aged 6-8 weeks were continuously administrated with psoralen or positive control drug diallyl sulfide (DAS) intragastrically for 4 days.On day 4, except that the control group were treated with vehicle control, other groups were all given carbon tetrachloride intraperitoneally to establish a carbon tetrachloride acute liver injury model.Serum biochemical indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected; liver pathological changes were observed by HE staining; cytochrome P450 2E1 (CYP2E1) protein levels were detected by Western blot; the protein level of CYP2E1 were detected by immunohistochemistry (IHC) staining; and the gene levels of CYP2E1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by RT-PCR.Compared with the model group, psoralen could improve the inflammatory cell infiltration and hepatocyte necrosis caused by carbon tetrachloride, significantly reducing the serum ALT and AST levels, down-regulating the inflammatory factors TNF-α and IL-6 levels, and inhibiting CYP2E1 protein expression.The results show that psoralen can ameliorate the acute liver injury induced by carbon tetrachloride in mice, with the possible mechanism inhibiting the protein expression of CYP2E1.

Effect of Psoralen on Osteoporosis in Postmenopausal Rats and PI 3K/Akt/mTOR Signaling Pathway / 中国药房

OBJECTIVE：To stu dy the effect of psoralen on osteoporosis in postmenopausal rats and PI3K/Akt/mTOR signaling pathway. METHODS ：Totally 60 healthy female SD rats were randomly divided into normal group ，model group ，positive control group（0.09 mg/kg estradiol ），psoralen low-dose ，medium-dose and high-dose groups （22，44，88 mg/kg），with 10 rats in each group. Except for normal group ，the other groups were ovariectomized to establish Postmenopausal osteoporosis model. After 2 months of normal feeding after operation ，normal group and model group were given the constant volume of normal saline intragastrically，and administration groups were given the corresponding solution intragastrically ；the volume was 0.005 mL/g， once a day ，for consecutive 98 days. 24 h after last administration ，the BMD of femur and vertebra of right lower extremities in rats was determined. The contents of serum calcium ，osteocalcin and P1NP，the serum levels of BMP2 and VEGF were determined；mRNA and protein expression of PI3K，Akt and mTOR in femur tissue were detected.RESULTS ：Compared with normal group ，BMD of femur and vertebra ，serum contents of calcium ，osteocalcin，P1NP and serum levels of BMP 2，VEGF in model group were decreased significantly ，while the mRNA and protein expression of PI 3K，Akt and mTOR were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ，BMD of femur and vertebra ，serum levels of calcium ， osteocalcin，P1NP and serum levels of BMP2（except for psoralen medium-dose group ），VEGF（except for psoralen medium-dose group）were increased significantly in psoralen medium-dose and high-dose groups ，positive control group ，while the mRNA expression（except for psoralen low-dose group ）and protein expression of PI 3K，Akt and mTOR in administration groups were decreased significantly （P＜0.05 or P＜0.01）；BMD of femur ，serum levels of calcium ，BMP2 and PI 3K protein expression in psoralen high-dose group were significantly higher than positive control group （P＜0.05），and mTOR mRNA expression in psoralen high-dose group was significantly lower than positive control group （P＜0.05）. CONCLUSIONS ：Psoralen can improve osteoporosis in postmenopausal rats ，the mechanism of which may b e associated with inhibiting PI 3K/Akt/mTOR signaling pathway.

Original Research Article (Experimental): Design and Development of Unani Emulgel for Vitiligo

"Background: Vitiligo is not only a cosmetic problem, but also a social and psychological problemworldwide with the prevalence rate being highest in India. Treatment is unsatisfactory in WesternSystem of Medicine. Unani System of Medicine (USM) possesses various drugs to treat vitiligo inboth topical and oral dosage forms. Safoof-e-Bars (SB) is an important powdered dosage form usedwidely to treat vitiligo, internally as Zulal. Externally as Sufl (Sediment remained after decanting thesoaked drug) is used. Babchi, a component of SB, is reported to contain psoralen, an importanttherapeutically active compounds for treating vitiligo. But as Psoralen e the active marker compound is very slightly soluble in water, so only negligible amount of it comes in zulal and most ofthe amount remains in sufl. That might be the reason for local application of sufl as recommendedby Hakeems. But clinically it is observed that application of sufl is not followed by most of thepatients, due to side effects associated with its application on skin.Objective: The present study is designed to convert Safoof-e-Bars into a more convenient and appealingnewly evolved dosage form ‘emulgel’ of same composition as of SB, so that it can be used by the patientseasily without any side effects.Materials & methods: Various batches of emulgel were prepared as preliminary batches and final batchesusing hydro-alcoholic extract of SB and different excipients in different concentrations. Preliminarybatches were formed for selecting composition and concentration of extract and excipients for finalbatches. Total eight batches (F1eF8) were prepared as final batches. Among these eight batches, batch F7was selected as final batch, which was further evaluated on various parameters. Comparative quantitative analysis was done in Zulal, Hydro-alcoholic extract of SB and emulgel using HPLC.Results: Optimized emulgel showed good result in physicochemical parameters. Highest percentage ofpsoralen was found in SB extract while lowest percentage was found in zulal. No growth of yeast andmould, and viable aerobic were found in emulgel on microbiological analysis. Emulgel was found to bestable for 3 months.Conclusion: Newly developed emulgel may be recommended with zulal instead of traditionally used suflwith zulal. In future emulgel will provide a solution for topical delivery of hydrophobic drugs and moreconvenient dosage form to apply locally."

Effects of psoralen corylifolia extract on bone mineral density and bone biomechanics in osteoporosis rats / 中国组织工程研究

BACKGROUND: Long-term use of dexamethasone as a glucocorticoid will destroy the dynamic balance of osteogenesis and osteoclastation, reduce bone mineral density, damage bone biomechanics. A regulation of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) protein pathway may be an approach to improve bone mineral density and bone biomechanics in dexamethasone-induced osteoporosis rats. OBJECTIVE: To investigate the effects of psoralen corylifolia extract on bone mineral density and bone biomechanics in dexamethasone-induced osteoporosis rats based on RANKL/OPG pathway. METHODS: Osteoporosis models were established in Wistar rats, SPF grade, using intramuscular injection of dexamethasone. Lentiviral vectors containing OPG gene interference fragments at concentration of 1×107 TU/mL were selected for subsequent experiments. The model rats were randomly divided into model group, no-load group (lentivirus empty vector), OPG silencing group (lentivirus vector containing OPG gene interference fragment), psoralen corylifolia extract group, psoralen corylifolia extract+OPG silencing group, with 12 rats in each group. Another 12 rats were selected as the control group. After drug treatment, bone mineral density of the left femur in rats was measured by bone densitometer; the elastic modulus, maximum load and yield load of the right femur of rats were measured by mechanical testing machine; the mineral salt content in the femur of rats was determined; the levels of RANKL and OPG in the serum of rats were detected by ELISA kit; and the expression levels of RANKL and OPG in bone tissues of rats were detected by western blot. The study protocol was approved by the Animal Ethics Committee of Qinghai University Medical School with an approval No. 2017081501. RESULTS AND CONCLUSION: (1) Bone mineral density, modulus of elasticity, maximum load, yield load, bone mineral salt content, serum OPG level and OPG protein expression in bone tissues were measured, which were lower in the model group than the control group, lower in the OPG silencing group than the model group, higher in the psoralea corylifolia extract group than the model group, and higher in the psoralen corylifolia extract+OPG silencing group than the OPG silencing group, but lower than the psoralea corylifolia extract group (all P 0.05). (4) All these findings indicate that psoralea corylifolia extract can increase bone mineral density and improve bone biomechanics in dexamethasone-induced osteoporosis rats, possibly by up-regulating the expression of OPG and down-regulating the expression of RANKL.

Psoralen induces proliferation of rabbit endosteal mesenchymal stem cells and constructs cell-scaffold bone complex innonunionrepair / 中国组织工程研究

BACKGROUND: Psoralen is a plant estrogen, and a large number of studies have confirmed its role in promoting cell proliferation and differentiation. OBJECTIVE: To construct a cell-scaffold composite bone using psoralen, rabbit endosteal mesenchymal stem cells and polycaprolactone and to explore its effect on the treatment of rabbit nonunion. METHODS: (1) Rabbit endosteal mesenchymal stem cells were cultured and cultured until the third generation for each experiment. Passage 3 cells were seeded onto culture plates containing 50 mg/L bone morphogenetic protein 2 (positive control), 10-8, 10-7 and 10-6 mol/L psoralen (low-, middle-, and high-concentration psoralen groups) or the same volume of purified water (control group). The cell proliferation of each group was detected on the 3rd, 5th and 7th days after intervention using MTT method. (2) The three-dimensional polycaprolactone scaffold was added to the bottom of the cell culture plate, and rabbit endosteal mesenchymal stem cells were seeded into the scaffold at a density of 1×103 per well. Then, 10-6 mol/L of psoralen was added. Cell-scaffold composite bone was taken after 21 days of culture. (3) Animal models of radial nonunion were established in 27 New Zealand white rabbits, and were then randomized into experimental, scaffold and control groups followed by implantation of cell-scaffold composite bone, simple scaffold, and nothing, respectively. Pathological hematoxylin-eosin staining for observation of bone healing was performed at the 2nd, 4th, and 8th weeks after surgery. Healing of nonunion was observed on the X-ray films that were taken at the 4th week after surgery. RESULTS AND CONCLUSION: (1) Three concentrations of psoralen could induce the proliferation of rabbit endosteal mesenchymal stem cells. Compared with the control group, 10-6 mol/L psoralen exerted the strongest stimulation effect on rabbit endosteal mesenchymal stem cells (P 0.05). (2) Pathological hematoxylin-eosin staining of radial nonunion showed that the number of osteoblasts in the experimental group was higher than that in the scaffold and control groups (P < 0.05). (3) The X-ray films revealed bone healing in the experimental group, partial healing in the scaffold group and non-healing in the control group. Overall findings indicate that psoralen can promote the proliferation of rabbit endostealmesenchymal stem cells, and the effect is certainly related to the concentration of psoralen. Psoralen can be combined with rabbit endosteal mesenchymal stem cells and polycaprolactone scaffold to form composite bone, achieving good outcomes in the treatment of nonunion in animals.

Mechanism of psoralen in aggravating hepatotoxicity induced by CCl_4 by delaying liver regeneration / 中国中药杂志

This study aimed to investigate whether psoralen can aggravate hepatotoxicity induced by carbon tetrachloride(CCl_4) by inducing hepatocyte cycle arrest and delaying liver regeneration. Female C57 BL/6 mice aged 6-8 weeks were randomly divided into control group, model group(CCl_4 group), combined group(CCl_4+PSO group) and psoralen group(PSO group). CCl_4 group and CCl_4+PSO group were given CCl_4 intraperitoneally at a dose of 100 μL·kg~(-1) once; olive oil of the same volume was given to control group and PSO group intraperitoneally; 12 h, 36 h and 60 h after CCl_4 injection, PSO group and CCl_4+PSO group were administrated with PSO intragastrically at a dose of 200 mg·kg~(-1); 0.5% CMC-Na of the same volume was administrated to control group and PSO group intragastrically. The weight of mice was recorded every day. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured at 36 h, 60 h and 84 h after CCl_4 injection. Mice were sacrificed after collection of the last serum samples. Liver samples were collected, and liver weight was recorded. Histopathological and morphological changes of liver were observed by haematoxylin and eosin staining. The mRNA levels of HGF, TGF-β, TNF-α, p53 and p21 in liver were detected by RT-qPCR. Western blot was used to detect the levels of cell cycle-related proteins. According to the results, significant increase of serum ALT and AST and centrilobular necrosis with massive inflammatory cell infiltration were observed in CCl_4+PSO group. After PSO administration in CCl_4 model, the mRNA levels of HGF(hepatocyte growth factor) and TNF-α were reduced, while the mRNA expressions of TGF-β, p53 and p21 was up-regulated. The expression of PCNA(proliferating cell nuclear antigen) was significantly increased in CCl_4 and CCl_4+PSO group, while the relative protein level in CCl_4+PSO group was slightly lower than that in CCl_4 group. Compared with control and CCl_4 group, the expression of p27(cyclic dependent kinase inhibitor protein p27) was prominently increased in CCl_4+PSO group. These results indicated that hepatotoxicity induced by CCl_4 could be aggravated by intraperitoneal administration with PSO, and the repair process of liver could be delayed. The preliminary mechanism may be related to the inhibition of PCNA and regulation of some cell cycle-associated protein by psoralen, in which the significant up-regulation of p27, p53 and p21 may play important roles.

Effect of psoralen on rat osteoblasts injuries induced by TCP wear particles in vitro and its mechanism / 中国应用生理学杂志

To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro. Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10, 10, 10 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

To determine irradiance of ultraviolet A in ambient sunlight and optimum exposure time for PUVAsol in a North Indian location

Background: Psoralen with ultraviolet A is an effective photochemotherapeutic modality. A subtype of this, PUVAsol, uses sunlight as the natural source of ultraviolet A. The amount of sunlight received and the consequent ultraviolet A exposure vary according to the month in the year, time of the day and geographical location of a place. Aim: The aim of this study is to determine irradiance of ultraviolet A in ambient sunlight and optimum exposure time for PUVAsol. Materials and Methods: This was an observational study carried out at Postgraduate Institute of Medical Education and Research, Chandigarh (30.7333°N, 76.7794°E), India using a photometer. Ultraviolet A irradiance was recorded at a fixed place at 10 AM, once weekly for a period of 12 months. Results: The irradiance of peak ultraviolet A was found to be 3.1 mW/cm2 in June 2016 while irradiance of 0.64 mW/cm2 was recorded in January 2017. The exposure time needed for therapeutic dose of 2 J/cm2 was 11 min 6 s in June 2016 while exposure time for achieving therapeutic dose of 2 J/cm2 was 52 min 5 s in January 2017. The duration of exposure was found to be significantly longer in the winter months. Limitation: The limitation of the study is not determining ultraviolet B radiation and infrared exposure. Other limitation of this study is that the irradiance was measured only at 10 am. This data cannot be used to determine irradiance at different time points in the day as the patient may expose himself/herself to sunlight anytime depending on his/her convenience. Conclusions: The study demonstrates the mean exposure time required for a given therapeutic dose of ultraviolet A in different months. The wide variation in ultraviolet A irradiance in natural sunlight over the year in different months also suggests that exposure times for PUVAsol should be based on the season and geographical location at the site of therapy and not based on uniform guidelines.

An Experimental Study Of Vrikshayurveda Seed Treatments On Germination Rate And Active Ingredient Of Bakuchi (psoralea Corylifolia Linn.) By Hplc Method

Bakuchi (Psoralea corylifolia Linn.) is one of the important endangered medicinal plants used in Ayurveda and other Traditional systems. Its cultivation and propagation is difficult due to its low germination rate (5-7%) & prolonged seed dormancy. Bakuchi seeds made into 5 groups, the experiment was conducted in a complete randomized block design with 5 treatments and 5 replications totally 500 seeds in each group) & observed for 50 days. Control Group 1 no- seed treatment, Group 2- Standard treated with 1% conc H2SO4, Group 3 Vrikshayurvedic treatment done by soaking in milk subsequently fumigation of Vidanga & Ghee, Group 4- treated with paste of Brihati, Tila, Kamalanaala, Ghee & Group 5 treated by soaking in milk subsequently Cow dung, Vidanga & Honey applied. Number of seeds germinated, germination percentage, emergence index and relative seed germination parameters were observed. HPLC studies carried out of post harvested Bakuchi seeds of all 5 groups to know the effect of seed treatments on Psoralen content quantitatively. Overall results indicates that Group 4 (8.000 ± 0.8367) seeds soaked in 12 hrs milk followed by application of Brihati, Tila, Kamalanaala & Ghee paste for 12 hrs treatment is statistically significant (P value>0.05) in comparison with group 2 (4.600 ± 0.6782) Sulphuric acid treatment and Group 3 (4.200± 0.9165) fumigation with Honey & Vidanga. Rest of the groups shown insignificant changes on germination parameters. HPLC Results found that generally seed treatments may reduce the content of Psoralen as in control (Group 1) maximum percentage (0.04%w/w) of Psoralen is noticed. Among treatment groups Group 4 contains maximum (0.027%w/w) Psoralen next to control (0.039%w/w). Psoralen content is very less in standard Group 2 (0.022%w/w), Group 3 (0.023%w/w) & Group 4 (0.024%w/w). Maximum germination percentage was observed in Group 4 in comparison with the Group 2conventional method of treating with sulphuric acid. Estimation of Psoralen contents in the seeds from the plants grown by various treated seeds reveled that Group 4 is qualitatively better than standard, but inferior to the control, standard & other Vrikshayurveda seed treatment techniques used in the current experiment.

Psoralen inhibits malignant proliferation and induces apoptosis through triggering endoplasmic reticulum stress in human SMMC7721 hepatoma cells

BACKGROUND: Psoralen is a coumarin-like and coumarin-related benzofuran glycoside, which is a commonly used traditional Chinese medicine to treat patients with kidney and spleen-yang deficiency symptom. Psoralen has been reported to show estrogen-like activity, antioxidant activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. However, the antitumor mechanism of psoralen is not fully understood. This study aimed to investigate the therapeutic efficacy of psoralen in human hepatoma cell line SMMC7721 and the mechanism of antitumor effects. RESULTS: Psoralen inhibited proliferation of SMMC7721 in a dose- and time-dependent manner, and promoted apoptosis. Further, psoralen activated the ER stress signal pathway, including the expansion of endoplasmic reticulum, increasing the mRNA levels of GRP78, DDIT3, ATF4, XBP1, GADD34 and the protein levels of GDF15, GRP78, IRE1α, XBP-1s in a time-dependent manner. Psoralen induces cell cycle arrest at G1 phase by enhancing CyclinD1 and reducing CyclinE1 expression. Moreover, TUDC couldn't inhibit the psoralen-induced ER stress in SMMC7721 cells. CONCLUSIONS: Psoralen can inhibit the proliferation of SMMC7721 cells and induce ER stress response to induce cell apoptosis, suggesting that psoralen may represent a novel therapeutic option for the prevention and treatment hepatocellular carcinoma.

Study on the Vasodilatory Effect Mechanism of Psoralen and Bakuchiol / 中国药房

OBJECTIVE： To investigate the vasodilatory effect mechanism of psoralen and bakuchiol. METHODS： The rat thoracic aorta was isolated to prepare vascular rings and de-endothelium vascular rings. Using contraction rate as index， the intact endothelium or de-endothelium vascular rings were pre-incubated with N-nitro-L-arginine methyl ester （L-NAME， 100 μmol/L）； vasodilatory effect of low-dose， medium-dose and high-dose of psoralen or bakuchiol（0.1，1，10 μmol/L）on aortic vessels pre- contracted with norepinephrine （NE， 1 μmol/L） or potassium chloride （KCl， 60 mmol/L） were investigated. The de-endothelium vascular rings were pre-incubated with calcium dependent potassium channel inhibitors tetraethylammonium chloride （TEA， 0.1 mmol/L） and inward rectifying potassium channel inhibitor barium chloride （BaCl2，0.1 mmol/L）； vasodilatory effect of low-dose， medium-dose and high-dose of bakuchiol （0.1， 1， 10 μmol/L） on de-endothelium vascular vessels pre-contracted with NE （1 μmol/L） were investigated. The microvascular endothelial cells were isolated by collagenase-neutral protease digestion； the effects of low-dose， medium-dose and high-dose of psoralen or bakuchiol （0.1， 1， 10 μmol/L） on the expression of eNOS protein were studied by ELISA. RESULTS： Psoralen and bakuchiol could significantly reduce the contraction rate of endothelium-intact aortic rings pre-contracted with NE（P＜0.01）； medium-dose and high-dose of psoralen and bakuchiol could significantly reduce the contraction rate of  endothelium-intact aortic rings pre-contracted with KCl（P＜0.05 or P＜0.01）； while the contraction rate could be increased by de-endothelium and NOS inhibition significantly （P＜0.05 or P＜0.01）. The medium-dose and high-dose of bakuchiol could significantly reduce the contraction rate of  de-endothelium vascular vessels pre-contracted with NE （P＜0.05 or P＜0.01）. The contraction rate could be increased by inhibiting inward rectifier potassium channels in vascular smooth muscle （P＜0.01）. Different dosages of psoralen and bakuchiol could significantly increase the expression levels of eNOS protein in rat cardiac microvascular endothelial cells（P＜0.01）. CONCLUSIONS： Psoralen and bakuchiol may play a role in vasodilation via endothelium-dependent NO pathway and by promoting eNOS protein expression in endothelial cells； bakuchiol may play a role in vasodilation via non-endothelium dependent pathway as opening inward rectifying potassium channel.

Analysis of standard decoction of salt-processed Psoraleae Fructus / 中国中药杂志

The traditional Chinese medicine standard decoction is prepared on the basis of the theory of traditional Chinese medicine and clinical application. With reference to the modern extraction method,the single decoction of traditional Chinese medicine is prepared by the standardized process,and the establishment of its quality standards is conducive to standardizing clinical medication. This research is to set an evaluation standard for the quality of salt-processed Psoraleae Fructus standard decoction. Twelve batches of salt-processed Psoraleae Fructus standard decoctions were prepared. The contents of psoralen and isopsoralen were determined,the transfer and extract rates were calculated,and the pH value was measured; HPLC fingerprint method was established for analysis. The results of the 12 batches of samples revealed that the transfer rates of psoralen and isopsoralen were 17. 10%-26. 40%,14. 70%-22. 70%,respectively; the extract rate was between 14. 7%-27. 0%,and the pH value was between 5. 4-6. 9. Moreover,7 common chromatographic peaks were determined based on fingerprint by using similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine( 2012 A).The similarities of the 12 batches of samples were analyzed and compared,and the results showed that the similarities were all higher than0. 9. In this study,the preparation method for salt-processed Psoraleae Fructus decoction was standard,with high similarities in fingerprint. This study build a convenient and reliable method of comprehensive quality evaluation,with a high precision,stability and repeatability,which can provide a reference for the quality control of salt-processed Psoraleae Fructus dispensing granules.

Psoralen and isopsoralen improve lipid metabolism disorder via inhibition of NF-κB activation in LO2 cells / 中国中药杂志

The aim of this paper was to investigate the mechanism and effect of psoralen and isopsoralen in the treatment of lipid accumulation in LO2 cells. Human LO2 cells nonalcoholic fatty liver models were established by using palmitic acid( PA). Then psoralen and isopsoralen were administered for intervention. Intracellular triglyceride( TG) and total cholesterol( TC) content,the cell supernatant alanine aminotransferase( ALT) and aspartate aminotransferase( AST) levels were determined by enzyme method. Cell supernatant proinflammatory cytokines( IL-6,TNF-α) and chemokines( IL-8,MCP-1) were determined by ELISA method. Western blot method was conducted to detect the protein expression of intracellular nuclear factor( NF-κB) p65 phosphorylation( p-p65),nonphosphorylated protein( p65),and transforming factor TGF-β1. Result showed that as compared with the model group,intracellular TG and TC levels,the cell supernatant ALT and AST levels,proinflammatory cytokines and chemokines were decreased( P < 0. 01,P <0. 05); the p-p65/p65 ratio and TGF-β1 protein expression were also significantly decreased( P< 0. 01,P< 0. 05) in psoralen intervention group. As compared with the model cells,intracellular TG content had no significant changes,but all the other indexes were reduced( P<0. 01,P<0. 05) in the cells of isopsoralen intervention group. Psoralen exhibited better effect than isopsoralen( P< 0. 01,P<0. 05). It is concluded that psoralen could improve the adipogenesis of LO2 cells induced by PA; both psoralen and isopsoralen are effective in ameliorating LO2 cells injury induced by PA,reducing inflammation via inhibiting the activation of NF-κB and down-regulating the expression of TGF-β1.

Advance in phytoestrogenic effects of psoralen / 上海交通大学学报（医学版）

Psoralen is one of the effective ingredients extracted from Chinese herbal medicine Psoralea corylifolia. Studies have found that psoralen has an estrogenic effect and can regulate the estrogen receptor. Psoralen can exert phytoestrogenic effects such as anti-tumor, anti-osteoporosis, anti-oxidation and protection of cardiovascular. This article reviewed the research progress of phytoestrogenic effects of psoralen.

Formulation optimization, in situ intestinal absorption and permeability of psoralen and isopsoralen / 中草药·英文版

Objective: To optimize a self-emulsifying drug delivery system (SEDDS) formulation for psoralen and isopsoralen (PSO and IPSO) isolated from Psoraleae Fructus. Methods: A D-optimal design was used to investigate the influence of oil percentage, surfactant percentage and cosurfactant percentage on several properties of SEDDS including particle size, polydispersity, equilibrium solubility, in situ intestine absorption rate and intestinal permeability. Furthermore, the desirability function approach was applied to obtain the optimal formulation for the system. Results: The oil percentage, surfactant percentage and cosurfactant percentage were optimized to be 53.6%, 35.7% and 10.7%, respectively, which means the model is available. Conclusions: The D-optimal design is valuable to optimize the SEDDS formulation and understand formulation compositions’ functions on SEDDS properties.

Validation of a photostability indicating method for quantification of furanocoumarins from Brosimum gaudichaudii soft extract

ABSTRACT A validation study of a reverse-phase high-performance liquid chromatographic assay for the quantification of two furanocoumarins (psoralen and bergapten) in soft extract obtained from Brosimum gaudichaudii Trécul, Moraceae, roots was conducted. The developed method was sensitive, rapid, reproducible, easy and precise, and showed linearity (r > 0.99) in the range of 10-64 µg/ml for psoralen, and 9-56 µg/ml for bergapten. It also showed a good efficiency for the photodegradation analysis of psoralen and bergapten in the soft extract. The photostability results showed that the Higuchi model presented the best fitting to the obtained data. Both chemical markers showed stability over 2.6 days, suggesting potential applications of the extract in obtaining intermediate products from this plant material. Furanocoumarins take around 30 min to be activated by UV light, reaching the maximum biological potential. Thus, the results obtained to the Higuchi model, corresponding to 2.6 days of stability, shows feasibility with future applications of these chemical markers.

Quality evaluation system for standard decoction of salt-processed Psoraleae Fructus / 中草药

Objective To establish a quality evaluation system for standard decoction of salt-processed Psoraleae Fructus (PF). Methods Fifteen batches of crude drugs were collected and processed into decoction pieces with salt complied with the 2015 Edition of the Chinese Pharmacopoeia, and then the standard decoctions of salt-processed PF were prepared as freeze-dried powders. Based on the established HPLC fingerprint, seven common peaks were recognized and the main chemical constituents were identified in combination with time-of-flight mass spectrometry. Results Benzofuran glycosides and furanocoumarins turned out to be the main composition of standard decoction of salt-processed PF. The dry extract yielding rate varied from 16.31% to 20.59%, while the total contents of psoralen and isopsoralen were 1.17%—1.50% with a transfer rate ranging from 13.55% to 23.57%, and the fingerprint similarity of 15 batches of samples were all higher than 0.9. Conclusion This stable and reliable method of comprehensive quality evaluation for standard decoction of salt-processed PF may provide reference for quality control of salt-processed PF dispensing granules and related preparations.

Cloning and expression analysis of GlPS1, GlPS2 gene in Glehnia littoralis / 中草药

Objective: To clone the full-length cDNA sequences of psoralen synthase (PS) genes from Glehnia littoralis so as to perform the bioinformatic and expression pattern analysis. Methods: Based on our previous transcriptome sequencing data of G. littoralis, the gene sequences GlPS1 and GlPS2 with high expression level were screened. The 3’cDNA ends of GlPS1 and GlPS2 genes were cloned by the RACE (rapid amplification of cDNA ends) method and the full-length cDNA of genes were assembled by using DNAMAN software. And then encoded GlPS proteins were analyzed by the bioinformatics tools. The issue specific expression of GlPS1 and GlPS2 genes were detected using qPCR. Results: The full-length cDNA of GlPS1 gene was 1 885 bp, which encoding a protein of 495 amino acids with a predicted molecular weight of 55 740.7 and isoelectric point of 8.28; The full-length cDNA of GlPS2 gene was 1 971 bp, which encoding a protein of 502 amino acids with a predicted molecular weight of 56 363.9 and isoelectric point of 6.62. GlPS1 and GlPS2 proteins belong to the cytochrome P450 superfamily, which share one transmembrane zone acting as hydrophilic protein. Phylogenetic analysis showed GlPS1 and GlPS2 were genetically closely related to the PS of Pastinaca sativa, Apium graveolens, Ammi majus. Higher expression of GlPS1 gene was observed in roots than leaves. However, GlPS2 gene was expressed at a relatively higher level in flowers than in roots. Conclusion: The full-length cDNA of GlPS1 and GlPS2 genes were obtained and the expression patterns were explored in G. littoralis for the first time, which provided a foundation for further studies on gene function and genetic regulatory mechanism of GlPS.