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1.
Journal of Peking University(Health Sciences) ; (6): 792-796, 2018.
Article in Chinese | WPRIM | ID: wpr-941703

ABSTRACT

OBJECTIVE@#To establish a high performance liquid chromatography (HPLC) method for the determination of 8-methoxypsoralen (8-MOP) in mouse plasma and apply it to a pharmacokinetic study of 8-MOP.@*METHODS@#8-MOP was separated on a Waters Symmetry18 column (250 mm × 4.6 mm, 5 μm) and determined by HPLC using isocratic elution, and 5-methoxypsoralen was used as internal standard. The mobile phase consisted of methanol-water (55:45, V/V) at a flow rate of 1.0 mL/min. The excitation and emission wavelength of fluorescence detector were set at 334 nm and 484 nm respectively, and the internal standard method was used for quantitative analysis. In the study, 60 healthy ICR male mice were randomly divided into twelve groups. The mice in control group were administered intragastrically with 1% Tween 80, and the mice in the other eleven groups were administered intragastrically with 8-MOP (40 mg/kg). Plasma concentrations of 8-MOP in the mice at different time points after treatment were determined by HPLC. Pharmacokinetic parameters were calculated by DAS 2.0 software.@*RESULTS@#The calibration curve of 8-MOP was linear with a correlation coefficient of 0.999 3 over the concentration range of 0.05 to 10 mg/L, and the limit of detection was 0.015 mg/L. The average recoveries of 8? MOP at three different concentrations (0.10, 0.50, 2.5 mg/L) were from 92.5% to 100.6%. The intra-day precision of 8-MOP was from 3.3% to 8.2%, while the inter-day precision was from 3.4% to 6.7% at three spiked concentration levels. The extraction recoveries of 8-MOP were from 90.9% to 92.0%, and the plasma samples could be stored at -80°C for 15 days at least at three spiked concentration levels. 8-MOP could be detected in mouse plasma 5 min after intragastrical administration to the mice (1.4 mg/L). The concentration of 8-MOP in the mouse plasma reached a maximum 2 h after administration, and 8-MOP could still be detected 24 h after administration (1.1 mg/L). t1/2 was (39.21±3.65) h, Cmax was (2.31±0.02) mg/L, tmax was (2.00±0.00) h, and AUC0-t was (33.34±1.19) (h×mg)/L.@*CONCLUSION@#The proposed method is accurate and simple,suitable for pharmacokinetics of 8-MOP in mice.


Subject(s)
Animals , Male , Mice , Calibration , Chromatography, High Pressure Liquid , Methoxsalen/pharmacokinetics , Mice, Inbred ICR , Photosensitizing Agents/pharmacokinetics , Plasma , Random Allocation
2.
An. bras. dermatol ; 92(5): 704-706, Sept.-Oct. 2017. graf
Article in English | LILACS | ID: biblio-887026

ABSTRACT

Abstract: Pigmented purpuric dermatoses are chronic vascular inflammatory conditions characterized by the presence of pigmented macules. Among its different presentations, lichen aureus is distinguished by the lichenoid conformation of its plaques and the predilection for lower limb involvement. Its segmented form is rare and difficult to control, especially in cases of symptomatic lesions. We report a rare case of segmental lichen aureus with six years of evolution associated with light itching. We also discuss the main therapeutic approaches to control the disease.


Subject(s)
Humans , Female , Middle Aged , Lichenoid Eruptions/pathology , Sunlight , Betamethasone/therapeutic use , Photosensitizing Agents/therapeutic use , Lichenoid Eruptions/therapy , Glucocorticoids/therapeutic use , Methoxsalen/therapeutic use
3.
China Journal of Chinese Materia Medica ; (24): 2148-2156, 2015.
Article in Chinese | WPRIM | ID: wpr-337968

ABSTRACT

The chemical constituents from lipophilic parts in the roots of Angelica dahurica var. formosana cv. Chuanbaizhi were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods on silica gel and HPLC, and the chemical structures of compounds were determined by spectral data analyses. Twenty-nine compounds were obtained and identified as isoimperatorin (1), β-sitosterol (2), imperatorin (3), bergapten (4), osthenol (5), xanthotoxin (6), isoimpinellin (7), dehydrogeijerin (8), phellopterin (9), isodemethylfuropinarine (10), 7-demethylsuberosin (11), alloimperatorin (12), xanthotoxol (13), isooxypeucedanin (14), alloisoimperatorin (15), demethylfuropinarine (16), 5-hydroxy-8-methoxypsoralen (17), oxypeucedanin methanolate (18), pabulenol (19), byakangelicin (20), marmesin (21), (+) -decursinol (22), heraclenol (23), oxypeucedanin hydrate (24), marmesinin (25), ulopterol (26), erythro-guaiacylglycerol-β-ferulic acid ether (27), threo-guaiacylglycerol-β-ferulic acid ether (28), and uracil (29). Compounds 5, 8, 11, 18, 21-23, and 26-28 were obtained from the roots of title plant for the first time.


Subject(s)
Angelica , Chemistry , Coumarins , Chemistry , Furocoumarins , Chemistry , Methoxsalen , Chemistry , Phytochemicals , Chemistry , Plant Roots , Chemistry
4.
Salvador; s.n; 2013. 65 p. ilus.
Thesis in Portuguese | LILACS | ID: lil-710689

ABSTRACT

Catecóis são derivados do benzeno, podendo apresentar citotoxicidade, que pode constituir um modelo experimental útil para o desenvolvimento de novos fármacos. No bioma brasileiro inúmeras plantas produzem metabólitos com atividades diversas, como antioxidantes, ou inibidores do crescimento celular. No Brasil, as neoplasias são a segunda causa de óbito, especialmente aquelas derivadas do sistema nervoso, aumentando o interesse por novos antineoplásicos e agentes neuroprotetores. Este trabalho caracteriza efeitos citotóxicos do 1,2-dihidroxibenzeno (CAT) e discretamina (DSC) em células do sistema nervoso in vitro. Determinou-se a EC50 de CAT e DSC usando brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium (MTT), investigou-se sua auto-oxidação por espectrofotometria, avaliou-se mudanças morfológicas e condensação/fragmentação nuclear por microscopia. Avaliou-se a proteção de DSC e 8-metoxipsoraleno (8-MOP) contra a citotoxicidade do CAT. O padrão de morte celular foi analisado por citometria de fluxo. A espoliação de glutation reduzido (GSH) foi analisada usando monoclorobimano. A toxicidade do CAT para células SH-SY5Y e C6 depende da dose e associa-se à formação de quinonas. Houve mudanças morfológicas, condensação/fragmentação da cromatina e morte apoptótica, não relacionada à espoliação de GSH. DSC não foi tóxica para células SH-SY5Y, porém protegeu contra os efeitos do CAT em baixas concentrações. DSC mostrou-se citotóxica para células de glioma (GL-15 e C6) e potencializou o CAT. Pré-tratamento por 30 minutos com DSC protegeu contra a ação do CAT após 72 horas. 8-MOP potencializou os efeitos do CAT, não revertendo seus efeitos na viabilidade celular, morfologia celular, condensação/fragmentação nuclear, e espoliação de GSH. Esses resultados caracterizam um modelo de citotoxicidade que pode ser aplicado no desenvolvimento de novos agentes farmacológicos. Estudos complementares são necessários para elucidar a proteção da DSC.


Catechols are benzene derivatives, which may exhibit cytotoxic activity that can be employed to develop new drugs. Plants are important sources of metabolites with pharmacological activities such as antioxidants, or cell growth inhibitors. In Brazil, cancer is the second leading cause of death, especially those derived from the nervous system, which increase the interest for new antineoplastic and neuroprotective drugs. The cytotoxic effects promoted by 1,2-dihydroxybenzene (CAT) and discretamine (DSC) in nervous system cells were characterized in vitro. The protective effects of DSC and 8-methoxypsoralen (8-MOP) against CAT-induced cytotoxicity were also evaluated. CAT and DSC EC50 was determined by using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT). CAT auto-oxidation was investigated by spectrophotometry. Morphological changes and nuclear condensation/ fragmentation were evaluated by microscopy. The pattern of cell death was obtained by flow cytometry. Reduced glutathione (GSH) depletion was analyzed by using monochlorobimane. CAT induced a dose-dependent toxicity to SH-SY5Y and C6 cells, associated with reactive quinones formation. It also induced morphological changes, nuclear condensation/fragmentation, and apoptotic death not caused by GSH depletion. DSC was not toxic to SH-SY5Y cells, but protected against CAT effects at low concentrations. DSC was be cytotoxic to glioma cells (GL-15 and C6) and potentiated CAT effects. However, pretreatment for 30 minutes with DSC protected them against CAT after 72 hours. 8-MOP also potentiated CAT effects instead to protect cells. These results characterize an experimental model useful for studies searching new pharmacological agents. However, further studies are needed to elucidate the DSC protective effects.


Subject(s)
Humans , /administration & dosage , /analysis , /pharmacology , /therapeutic use , Methoxsalen/analysis , Methoxsalen/pharmacology , Methoxsalen/therapeutic use , Neoplasms/pathology , Neoplasms/prevention & control
5.
China Journal of Chinese Materia Medica ; (24): 941-945, 2012.
Article in Chinese | WPRIM | ID: wpr-356039

ABSTRACT

<p><b>OBJECTIVE</b>To study the chemical constituents from the seeds of Notopterygium franchetii.</p><p><b>METHOD</b>Ethanol extracts of seeds N. franchetii were separated and purified by such methods as normal and reversed phase column chromatographies and thin-layer chromatography and structurally elucidated by MS and NMR evidences.</p><p><b>RESULT</b>Twenty nine compounds were separated, they were isoimperatorin (1), [3-sitosterol (2), phellopterin (3), bergapten (4), N-tetra, hexa, octacosanoylanthranilic acid (5-7), daucosterol (8), oxypeucedanin hydrate (9), umbelliferone (10), demethylfuropinnarin (11), (2S, 3S, 4R, 8E)-2-[(2'R)- 2'-hydroxydoco, trico, tetraco, entaco, hexaco sanosylamino] -octadecene-1, 3, 4-triol (12-16), (-)-oxypeucedanin (17), diosmetin (18), bergaptol-O-beta-D-glucopyranoside (19), nodakenin (20), 1'-O-beta-D-glucopyranosyl-(2R, 3S)-3-hydroxynodakenetin (21), uracil (22), decuroside V (23), 8-O-beta-D-glucopyranosyl-5-hydroxypsoralen (24), 8-O-beta-D-glucopyranosyl-5-methoxylpsoralen (25), diosmin (26), alaschanioside C (27), kynurenic acid (28) and mannitol (29).</p><p><b>CONCLUSION</b>All of these compounds were separated from the seeds of N. franchetii for the first time. Of them, 18, 22, 26 and 29 were firstly obtained from genus Notopterygium.</p>


Subject(s)
Apiaceae , Chemistry , Chromatography, Thin Layer , Coumarins , Chemistry , Diosmin , Chemistry , Flavonoids , Chemistry , Furocoumarins , Chemistry , Glucosides , Chemistry , Kynurenic Acid , Chemistry , Magnetic Resonance Spectroscopy , Mannitol , Chemistry , Methoxsalen , Chemistry , Seeds , Chemistry , Sitosterols , Chemistry , Uracil , Chemistry
6.
China Journal of Chinese Materia Medica ; (24): 381-383, 2012.
Article in Chinese | WPRIM | ID: wpr-274338

ABSTRACT

<p><b>OBJECTIVE</b>To determine bergapten's concentration in plasma and observe its pharmacokinetics in rats using a combined LC-MS/MS analytical method.</p><p><b>METHOD</b>Blood samples were separated on a Hypersil ODS column (4.6 mm x 250 mm, 5 mm) at a temperature of 30 degrees C, and mobile phase consisted of water and methanol (22.5: 77.5) at a flow rate of 0.8 mL x min(-1).</p><p><b>RESULT</b>The methodological study showed a good linear relationship of 8.12-162.4 g x L(-1) (r = 0.9999). The inner and inter-days relative standard deviations were both less than 10% , indicating legitimate precise and accuracy to the requirement of biological sample analysis.</p><p><b>CONCLUSION</b>The method is suitable for in vivo quantitative analysis for bergapten due to its accuracy, sensitivity and specificity. The pharmacokinetic process in rats forms a two-compartment model with first-order absorption.</p>


Subject(s)
Animals , Male , Rats , Chromatography, Liquid , Methoxsalen , Blood , Pharmacokinetics , Rats, Sprague-Dawley , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Tandem Mass Spectrometry , Time Factors
7.
Chinese Journal of Biotechnology ; (12): 781-789, 2011.
Article in Chinese | WPRIM | ID: wpr-324538

ABSTRACT

Anthrax is a zoonosis caused by Bacillus anthracis, which seriously affects human health. In recent years, a special phenomenon is found that the metabolic active of a bacterium remains after it is killed. To development of a KBMA (killed but metabolically active) Bacillus anthracis vaccine candidate strain, a plasmid pMAD and a recombinase system Cre-loxP were used to knockout the uvrAB gene of B. anthracis AP422 which lacks both of two plasmids pXO1 and pXO2. The results of PCR and RT-PCR shows that uvrAB genes were deleted from B. anthracis AP422 chromosome successfully. The constructed B. anthracis AP422deltauvrAB was inactivated by photochemical treatment (PCT) including an exposure in a long-wave-length ultraviolet (UVA) light and a treatment of 8-Methoxypsoralen (8-MOP), then the metabolic activity were detected by the method of MTS. The results showed that the killed B. anthracis AP422deltauvrAB maintained a highly metabolic activity for at least 4 hours, showing a state of KBMA. The KBMA strain of B. anthracis AP422deltauvrAB provides the prospective vaccine candidate strain for anthrax.


Subject(s)
Anthrax , Allergy and Immunology , Microbiology , Anthrax Vaccines , Genetics , Allergy and Immunology , Radiation Effects , Bacillus anthracis , Genetics , Allergy and Immunology , Gene Knockout Techniques , Methoxsalen , Pharmacology , Ultraviolet Rays , Vaccines, Inactivated , Genetics , Allergy and Immunology
8.
An. bras. dermatol ; 85(4): 571-572, jul.-ago. 2010. ilus
Article in Portuguese | LILACS | ID: lil-560595

ABSTRACT

Duas adolescentes e uma menina com vitiligo clinicamente diagnosticado foram tratadas com 8-metoxipsoraleno a 0,2 por cento em creme Lanette com subsequente exposição solar. Um ano após, apresentaram máculas acrômicas na área do vitiligo. A biópsia de pele em um dos casos revelou melanócitos com escassa pigmentação melânica. Os achados clínicos e histológicos sugerem o diagnóstico de leucodermia punctata.


Two adolescent females and a girl, all with clinically diagnosed vitiligo, were treated with 0.2 percent 8-methoxypsoralen cream followed by exposure to solar ultraviolet light. One year later, they developed hypopigmented and achromic spots on the areas affected by the vitiligo. Biopsy of skin tissue taken from one of these cases showed a marked reduction in melanin. Clinical and histological findings point to a diagnosis of leukoderma punctata.


Subject(s)
Adolescent , Child , Female , Humans , Methoxsalen/adverse effects , PUVA Therapy/adverse effects , Photosensitizing Agents/adverse effects , Pigmentation Disorders/etiology , Methoxsalen/therapeutic use , Photosensitizing Agents/therapeutic use , Pigmentation Disorders/pathology , Vitiligo/drug therapy
9.
China Journal of Chinese Materia Medica ; (24): 58-62, 2010.
Article in Chinese | WPRIM | ID: wpr-346946

ABSTRACT

<p><b>OBJECTIVE</b>To study the chemical constituents of Incarvillea younghusbandii.</p><p><b>METHOD</b>The chemical constituents were isolated by various column chromatographic methods and structurally identified by NMR and MS evidence.</p><p><b>RESULT</b>Fifteen compounds were obtained and identified as isobergapten (1), sphondin (2), imperatorin (3), xanthotoxin (4), phellopterin (5), heraclenol (6), rivulobirin A (7), methyl oleanolate (8), methyl caffeate (9), grevillic acid (10), boschniakinic acid (11), tert-O-beta-D-glucopyranosyl-(R)-heraclenol (12), 5-methoxy-8-O-beta-D-glucopyranosyloxypsoralen (13), 1'-O-beta-D-glucopyranosyl-3-hydroxynodakenetin (14) and phenylethyl-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (15).</p><p><b>CONCLUSION</b>All of these compounds were isolated from this plant for the first time and most of them are furocoumarins.</p>


Subject(s)
Benzopyrans , Chemistry , Bignoniaceae , Chemistry , Caffeic Acids , Chemistry , Coumarins , Chemistry , Furans , Chemistry , Furocoumarins , Chemistry , Magnetic Resonance Spectroscopy , Methoxsalen , Chemistry , Molecular Structure
10.
Journal of Southern Medical University ; (12): 2565-2567, 2010.
Article in Chinese | WPRIM | ID: wpr-267733

ABSTRACT

<p><b>OBJECTIVE</b>To establish a high-performance liquid chromatography (HPLC)-based method for determining the contents of psoralene, bergapten and apigenin in Ficus hirta Vahl.</p><p><b>METHODS</b>A Hypersil C18 column (250 mm × 4.6 mm, 5 µm) was used with the mobile phase of methanol-water (60:40), flow rate of 1.0 ml/min, detection wavelength of 268.7 nm and column temperature of 30 degrees celsius.</p><p><b>RESULTS</b>The calibration curve was linear within the range of 10.0-30.0 µg/ml for psoralene (r=0.9998), 15.0-45.0 µg/ml for bergapten (r=0.9998) and 5.0-15.0 µg/ml for apigenin (r=0.9992). The average recovery of psoralene was 99.7% (RSD=1.99%), that of bergapten was 99.9% (RSD=1.71%) and that of apigenin was 100.3% (RSD=1.78%).</p><p><b>CONCLUSION</b>The method is simple, economic and accurate with good reproducibility for the contents of psoralene, bergapten and apigenin.</p>


Subject(s)
Apigenin , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Chemistry , Ficusin , Methoxsalen
11.
Journal of Zhejiang University. Medical sciences ; (6): 348-351, 2009.
Article in Chinese | WPRIM | ID: wpr-310342

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of 8-methoxypsoralen on human melanocytes [Ca(2+)]i and cytoskeleton actin organization in vitro.</p><p><b>METHODS</b>Human melanocytes were obtained from normal foreskins. Laser confocal microscope was employed to measure [Ca(2+)]i and rhodamine-conjugated phalloidin was used to visualize the cytoskeleton actin.</p><p><b>RESULTS</b>8-methoxypsoralen increased [Ca(2+)]i and induced organization of actin stress fiber cytoskeleton.</p><p><b>CONCLUSION</b>8-methoxypsoralen might influence the migration of melanocytes by increasing the intracellular free Ca(2+) concentration and cytoskeleton actin reorganization.</p>


Subject(s)
Humans , Actins , Genetics , Calcium , Metabolism , Cell Movement , Cells, Cultured , Cytoskeletal Proteins , Genetics , Melanocytes , Cell Biology , Metabolism , Methoxsalen , Pharmacology , Skin , Cell Biology
13.
Acta Pharmaceutica Sinica ; (12): 505-510, 2007.
Article in Chinese | WPRIM | ID: wpr-268608

ABSTRACT

Fourteen compounds were isolated from the ethanol extraction of Saposhnikovia divaricata (Turcz.) Schischk using column chromatographic methods after enrichment by macroporous adsorptive resins. They were identified as fangfengalpyrimidine (1), clemiscosin A (2), 5-hydroxy-8-methoxypsoralen (3), sec-O-glucosylhamaudol (4), hamaudol (5), nodakenetin (6), prim-O-glucosylcimifugin (7), cimifugin (8), 4'-O-beta-D-glucosyl-5-O-methylvisamminol (9), 5-O-methylvisamminol (10), marmesin (11), adenosine (12), daucosterol (13) and beta-sitosterol (14) by physico-chemical properties and spectral data. Compound 1 is a new compound. Compounds 2 and 3 were isolated from umbelliferae plants and Saposhnikovia divaricata (Turcz.) Schischk for the first time respectively.


Subject(s)
Apiaceae , Chemistry , Chromatography, Thin Layer , Chromones , Chemistry , Coumarins , Chemistry , Heterocyclic Compounds, 4 or More Rings , Chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Methoxsalen , Chemistry , Molecular Conformation , Molecular Structure , Monosaccharides , Chemistry , Plant Roots , Chemistry , Plants, Medicinal , Chemistry , Pyrimidines , Chemistry , Resins, Synthetic , Xanthenes , Chemistry
14.
China Journal of Chinese Materia Medica ; (24): 1883-1885, 2007.
Article in Chinese | WPRIM | ID: wpr-307570

ABSTRACT

<p><b>OBJECTIVE</b>To develop an RP-HPLC method for simultaneous determination of 5 constituents in Fructus Cnidii.</p><p><b>METHOD</b>Analysis was performed on an Alltech C18 (4.6 mm x 250 mm, 5 microm) column. The mobile phases were acetonitrile water and acetic acid with gradient elution. The flow rate was 1 mL x min(-1). The monitoring wavelength was 325 nm and 245 nm. The column temperature was 40 degrees C.</p><p><b>RESULT</b>The linear response ranges were 1-20 microg x mL(-1) (r = 0.999 9) for xanthotoxin, 1-20 microg x mL(-1) (r = 0.999 9) for isopimpinellin, 11-20 microg x mL(-1) (r = 0.999 8) for bergapten, 100-1 200 microg x mL(-1) (r = 0.999 7) for imperatorin, 100-2 000 microg x mL(-1) (r = 0.999 9) for osthole. The average recoveries were all above 95%.</p><p><b>CONCLUSION</b>The method is simple, sensitive and accurate with good reproducibility.</p>


Subject(s)
Chromatography, High Pressure Liquid , Methods , Cnidium , Chemistry , Coumarins , Fruit , Chemistry , Furocoumarins , Methoxsalen , Plants, Medicinal , Chemistry , Reproducibility of Results
15.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 742-4, 2007.
Article in English | WPRIM | ID: wpr-635030

ABSTRACT

To establish a simple and reliable animal model of skin photo-damage, 20 mice were treated with 8-MOP and exposed to UVA (UVA 320-400 nm) for 24 h. After irradiation, the structure of the epidermis and dermis, collagen fibers, elastic fibers were observed by using HE staining and Weigert technique and compared with the normal controls. The acanthosis and epidermis proliferation with accompanying hyperkeratosis and parakeratosis were observed. Inflammatory infiltration was noted in the dermis. The elastic fibers became coarse, irregularly arranged and clustered, with their number increased. The collagen fibers showed obvious degeneration and some amorphous materials could also be observed. The blood vessels were irregularly dilated and vascular walls were thickened, with infiltration of inflammatory cells. It is concluded that murine photodamage model can be quickly, conveniently and reliably established by means of 8-MOP/UVA.


Subject(s)
Dermis/pathology , Disease Models, Animal , Epidermis/pathology , Methoxsalen/pharmacology , Photosensitizing Agents/pharmacology , Skin/pathology , Skin Aging , Ultraviolet Rays
16.
China Journal of Chinese Materia Medica ; (24): 2049-2052, 2006.
Article in Chinese | WPRIM | ID: wpr-246023

ABSTRACT

<p><b>OBJECTIVE</b>To study the chemical constituents from the fruits of Paliurus ramosissimus.</p><p><b>METHOD</b>The constituents of P. ramosissimus were separated with various chromatographic techniques and their structures were elucidated by means of spectral analysis and physico-chemical properties.</p><p><b>RESULT</b>Nine compounds were isolated and identified as umbelliferone (1), scoparone (2), aurapten (3), bergapten (4), isopimpinellin (5), byakangelicin (6), xanthotoxol (7), isosakuranin (8), poncirin (9).</p><p><b>CONCLUSION</b>Compounds 1-9 were isolated from the fruits of P. ramosissimus for the first time.</p>


Subject(s)
Coumarins , Chemistry , Fruit , Chemistry , Furocoumarins , Chemistry , Methoxsalen , Chemistry , Plants, Medicinal , Chemistry , Rhamnaceae , Chemistry , Umbelliferones , Chemistry
17.
Acta Pharmaceutica Sinica ; (12): 878-881, 2006.
Article in Chinese | WPRIM | ID: wpr-294921

ABSTRACT

<p><b>AIM</b>To investigate the penetration kinetics of xanthotoxin in human skin and stratum corneum.</p><p><b>METHODS</b>The penetration experiments were accomplished by the deposit of ethanolic xanthotoxin solution onto human skin and stratum corneum mounted on Franz cells. The diffused xanthotoxin in the receptor solution (1.4% human serum albumin) and the retained amount in the skin and in the stratum corneum after 24 h exposure were quantified by using high performance liquid chromatography.</p><p><b>RESULTS</b>Xanthotoxin flux was increased with the concentration deposited onto the human skin, and when the concentration is above 2.5 mg x mL(-1), there is no influence on the xanthotoxin flux. Similar results were obtained from the stratum corneum. And the peak time for the flux in the stratum corneum was preceded about 6 h earlier than that of the whole human skin. The retained xanthotoxin amount after 24 h exposure in the skin and in the stratum corneum increased according to the concentration deposited and has the tendency to saturate. The lag time of ethanolic xanthotoxin solution in the whole human skin is significantly higher than that in the stratum corneum (P < 0.05).</p><p><b>CONCLUSION</b>The characteristics of penetration kinetics of xanthotoxin will provide the information for concentration choice of topical formulation and give a reference for ultra violet A (UVA) irradiation time confirmation.</p>


Subject(s)
Female , Humans , Middle Aged , Administration, Cutaneous , Dose-Response Relationship, Drug , Epidermis , Metabolism , In Vitro Techniques , Methoxsalen , Pharmacokinetics , Photosensitizing Agents , Pharmacokinetics , Skin , Metabolism , Skin Absorption , Time Factors
18.
Article in English | IMSEAR | ID: sea-38118

ABSTRACT

BACKGROUND: Bath-PUVA-photochemotherapy has become a useful alternative to oral PUVA therapy due to a number of advantages over systemic PUVA, for example, no ophthalmologic risk and nausea, and a lower cumulative UVA doses. However, its major disadvantage is the logistical requirement for bath tubs in practice and some patients feel uncomfortable to share the same bath with others. Topical psoralen contained preparation may be a good candidate for safe, convenient, and useful regimen in the topical PUVA therapy. OBJECTIVES: The purpose of the present study was to investigate the intensity of the phototoxic response of 8-MOP bath solution to different concentrations of preparations of 8-MOP gels and creams. MATERIAL AND METHOD: Following informed consent, the test bath solution (0.375%), gels (0.0025% to 0.010%) and creams (0.0025% to 0.010%) were applied to the normal-appearing skin of the upper back of 23 volunteers who had no history of photosensitivity. The escalating UVA doses (0.25 to 7.0 J/cm2) were given 15 minutes after application of test substances. Seventy-two hours after UVA exposure minimal phototoxic doses (MPD) were defined visually and the intensity of the erythema response was also assessed by using a narrowband spectrophotometer The MPD and the dose-response curves for erythema response of the gels and creams were compared with those of the bath. RESULTS: There were no significant differences between the overall mean MPD of tested gels and that of bath solution (p > 0.05). On the contrary, the cream preparations induced phototoxic response (MPDs) to a lesser degree than bath solution and gels (p < 0.05). When comparing the slope of the dose-response curve for erythema of 0.0025% and 0.0100% gel to that of the bath solution, the correlation is very strong (R2 = 0.987 and 0.936, respectively, p < 0.0001). CONCLUSION: The present study shows that the threshold of phototoxic response of 0.0025% 8-MOP gel indicated by MPD is well correlated with those of the bath solution. The slope of the dose-response curve for erythema of this preparation also significantly corresponded to that of the bath solution. Thus, the penetration and drug delivery of 0.0025% 8-methoxypsoralen gel may be similar to 8-methoxypsoralen bath solution. This preparation may be a good candidate for a useful therapeutic modality for topical PUVA therapy, and further clinical trial should be performed.


Subject(s)
Administration, Topical , Adolescent , Adult , Aged , Baths , Dermatitis, Phototoxic/etiology , Dose-Response Relationship, Drug , Female , Gels , Humans , Male , Methoxsalen/administration & dosage , Middle Aged , PUVA Therapy , Photosensitizing Agents/administration & dosage
19.
Braz. j. med. biol. res ; 37(4): 559-568, Apr. 2004. ilus, tab, graf
Article in English | LILACS | ID: lil-357106

ABSTRACT

8-Methoxy psoralen (8-MOP) exerts a short-term (24 h) mitogenic action, and a long-term (48-72 h) anti-proliferative and melanogenic action on two human melanoma cell lines, SK-Mel 28 and C32TG. An increase of intracellular calcium concentration was observed by spectrofluorometry immediately after the addition of 0.1 mM 8-MOP to both cell lines, previously incubated with calcium probe fluo-3 AM (5 µM). The intracellular Ca2+ chelator BAPTA/AM (1 µM) blocked both early (mitogenic) and late (anti-proliferative and melanogenic) 8-MOP effects on both cell lines, thus revealing the importance of the calcium signal in both short- and long-term 8-MOP-evoked responses. Long-term biological assays with 5 and 10 mM tetraethylammonium chloride (TEA, an inhibitor of Ca2+-dependent K+ channels) did not affect the responses to psoralen; however, in 24-h assays 10 mM TEA blocked the proliferative peak, indicating a modulation of Ca2+-dependent K+ channels by 8-MOP. No alteration of cAMP basal levels or forskolin-stimulated cAMP levels was promoted by 8-MOP in SK-Mel 28 cells, as determined by radioimmunoassay. However, in C32TG cells forskolin-stimulated cAMP levels were further increased in the presence of 8-MOP. In addition, assays with 1 µM protein kinase C and calcium/calmodulin-dependent kinase inhibitors, Ro 31-8220 and KN-93, respectively, excluded the participation of these kinases in the responses evoked by 8-MOP. Western blot with antibodies anti-phosphotyrosine indicated a 92 percent increase of the phosphorylated state of a 43-kDa band, suggesting that the phosphorylation of this protein is a component of the cascade that leads to the increase of tyrosinase activity.


Subject(s)
Humans , Melanoma , Methoxsalen , Photosensitizing Agents , Potassium Channels , Protein-Tyrosine Kinases , Indoles , Signal Transduction , Spectrometry, Fluorescence , Time Factors , Tumor Cells, Cultured
20.
Korean Journal of Dermatology ; : 983-987, 2004.
Article in Korean | WPRIM | ID: wpr-215728

ABSTRACT

BACKGROUND: Photochemotherapy (PUVA) is the effective treatment for vitiligo. It is necessary to measure the minimal phototoxic dose (MPD) in order to ascertain a safe, effective UVA dose needed for irradiation during photochemotherapy. OBJECTIVE: The purpose of this study was to standardize the MPD for vitiliginous lesions. METHOD: The MPD was measured in 124 vitiligo patients. The number of patients monitored for topical and systemic MPD using the photosensitiser, 8-methoxypsoralen (8-MOP) were 41 and 83, respectively. MPD was also analysed according to sex, age, site of the vitiliginous lesions, duration of disease, season and administration route of the photosensitiser. RESULTS: 1. In the group assessed for topical application of 8-MOP cream, mean MPD was 0.62+/-0.59J/cm2. 2. In the group assessed for systemic administration of 8-MOP, mean MPD was 2.68+/-1.83J/cm2. 3. MPD in the group systemically administrated with 8-MOP was 4.32-fold to that of the topical application group (p<0.01). 4. In the case of both topical and systemic administration of the photosensitiser, 8-MOP, no significant differences in MPD were found due to the sex, age, site of vitiliginous lesions, duration of disease, or season in which MPD was administered to patients. CONCLUSION: There was a significant difference in MPD between the topical application group and the systemic administration group.


Subject(s)
Humans , Methoxsalen , Photochemotherapy , Seasons , Skin , Vitiligo
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