Isopsoralen

186.16

186.16

201-480-6

CZZ080D7BD

404563

DTXSID00200321

White crystalline solid

2932999099

39.4

2

Solid

1.4±0.1 g/cm3

142 °C

104°C/4mmHg(lit.)

173.1±23.7 °C

1.667

In water, 20 mg/L

2-8°C

9.7X10-6 mm Hg at 25 °C (est)

Slight hay-like odor

Henry's Law constant = 6.8X10-7 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 4.2X10-11 cu cm/mole-sec at 25 °C (est)|Ozone reaction rate constant = 2.1X10-17 cu cm/mole-sec at 25 °C (est)

NONH for all modes of transport

3

20/21/22-36/37/38-40

26-36/37/39-37/39-36

LV0940000

Xn,Xi

Stable under recommended storage conditions.

P261-P280-P305 + P351 + P338

H302 + H312 + H332-H315-H319-H335-H351

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 40 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Special hazards arising from the substance or mixture: Carbon oxides

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.|ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.|Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

IDENTIFICATION AND USE: Isopsoralen is a natural furocoumarin. It has been tested as experimental therapy. HUMAN STUDIES: Isopsoralen acted in vitro as ERalpha receptor agonists and promoted MCF-7 cell proliferation significantly. Angelicin forms DNA monoadducts when photoactivated. In human cells isopsoralen promoted sister-chromatid exchanges. ANIMAL STUDIES: Isopsoralen had potent tranquilizing, anticonvulsant, and central muscle relaxant activity in rats, mice, and rabbits when given both ip and orally. Isopsoralen was photomutagenic in bacterial and animal cells generating DNA monoadducts.

Photochemical genotoxicity can be detected using appropriately adapted versions of most of the standard in vitro genotoxicity assays. The most sensitive approach to detect potentially photogenotoxic agents seems to be the investigation of DNA damage (DNA strand breakage, chromosomal aberrations, micronuclei) in mammalian cells in vitro. In a previous paper, we proposed the use of the micronucleus assay in Chinese hamster V79 cells for this purpose. This assay was found suitable to detect various photogenotoxic compounds with different photoactivation mechanisms. In order to extend the experimental experiences with this assay, we present here further data from a screening mode testing of 16 different potential photosensitizers. The photoclastogenic and photocytotoxic potential of the compounds was investigated concomitantly. So far, all substances detected in the photo-micronucleus assay as photogenotoxins also exhibited photocytotoxic properties but not vice versa. Among the compounds tested in the present study, tiaprofenic acid, 5-MOP, angelicin, nitrazepam, bendroflumethiazide, and dacarbazine were photogenotoxic and photocytotoxic. Further, 6-mercaptopurine, a metabolite of azathioprine was positive for both endpoints, whereas azathioprine was found negative. Azathioprine seems to be an example of a compound which lacks photo(geno)toxic properties in vitro but may be converted to a photosensitizer by enzymatical metabolization. With the results obtained in this study, the data base for the photo-micronucleus assay was extended to 35 compounds, which were tested using the same protocol and the same irradiation conditions. The photogenotoxicity results of all these compounds are summarized and discussed in correlation to their different photoactivation mechanisms, photocytotoxicity and photocarcinogenicity.|In this study we have found that the crude extract of Psoraleae Fructus inhibited acetylcholinesterase activity in vitro and ameliorated impairment of the inhibitory avoidance response and of the water maze spatial performance caused by scopolamine in rats. Among all fractions, the chloroform fraction showed the best inhibitory effect on acetylcholinesterase activity and could reduce the scopolamine-induced inhibitory avoidance response impairment. Psoralen and isopsoralen, two major constituents of the chloroform fraction of Psoraleae Fructus identified by high performance liquid chromatography, also reduced the extent of the inhibitory avoidance response impairment. The results suggest that psoralen and isopsoralen are the major active ingredients of Psoraleae Fructus responsible for the progressive reversal of scopolamine-induced amnesia, whose effects are partially associated with inhibition of AchE activity and hence activation of the central cholinergic neuronal system.|Monofunctional psoralens, plus UVA radiation are not erythemogenic and are less mutagenic than bifunctional psoralens plus UVA radiation. Thus, they have received considerable attention in recent years as potential therapeutic agents for various skin diseases. The purpose of this study was to examine the immunologic side effects following treatment of mice with a monofunctional psoralen plus UVA radiation. We report that angelicin plus UVA radiation suppressed the induction of contact hypersensitivity to dinitrofluorobenzene. This decreased immune response was associated with the presence of splenic suppressor cells that transferred suppression to normal recipients. Treatment with angelicin and UVA radiation also decreased the number of Thy-1+ and Ia+ dendritic epidermal cells in the treated site. We conclude that although this monofunctional psoralen is not phototoxic, it has immunosuppressive activity in mice.|Because of the undesirable side effects associated with the use of 8-methoxypsoralen and long-wave ultraviolet A (UVA) radiation in the treatment of skin disorders such as psoriasis, the use of monofunctional psoralens, which are less erythemogenic, less mutagenic, and generally non-phototoxic, has received considerable attention. Little is known, however, about the immunosuppressive properties of monofunctional psoralens. The purpose of this study was to examine the effect of parenteral administration of a monofunctional psoralen, angelicin, plus exposure to UVA radiation on the immune response. Injection of angelicin followed by exposure to UVA radiation significantly suppressed delayed-type hypersensitivity to alloantigen in a dose-dependent fashion. Similarly, the capacity of spleen cells from the angelicin and UVA-treated animals to proliferate to alloantigen was significantly suppressed. The suppression was specific for the alloantigen used to sensitize the angelicin and UVA-treated animals and was associated with the appearance of splenic antigen-specific suppressor T lymphocytes. These data demonstrate that the effect of systemic administration of a monofunctional psoralen followed by UVA exposure on the immune response is similar to that seen following the injection of bifunctional psoralens. These findings also suggest that the severe skin phototoxicity associated with the use of a bifunctional psoralen and UVA radiation is not necessary for the induction of systemic immuno-suppression. Furthermore, the induction of systemic antigen-specific immunosuppression by angelicin plus UVA, without overt skin phototoxicity, suggests the possibility of using this and related compounds to specifically inhibit unwanted immune reactions.|For more Interactions (Complete) data for Isopsoralen (12 total), please visit the HSDB record page.

LD50 Mice i.p. 254 mg/kg|LD50 Rat i.p. 165 mg/kg|LD50 Rat oral 322 mg/kg

Isopsoralen occurs in various plants and plant parts(1). Isopsoralen has been isolated and detected in various Umbelliferae, including angelica (Angelica atropurpurea), parsnip (Pastinaca sativa) and several hogweed (Heracleum) species(2). Isopsoralen has been detected in the fresh fruiting heads of Heracleum mantegazzianum at 292 mg/100g; Isopsoralen has been detected at 0.5 mg/g in the root of H. sphondylium; concentrations in roots of H. laciniatum were circa 0.05 mg/g of root for Isopsoralen(3). Isopsoralen is a main active component of Psoralea corylifolia, a traditional Chinese medicine(3,4), and has antibacterial, anti-inflammatory, and antitumor activities(4).

Isopsoralen's production and use as a medical research chemical(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 102(SRC), determined from a log Kow of 2.08(2) and a regression-derived equation(3), indicates that isopsoralen is expected to have high mobility in soil(SRC). Volatilization of isopsoralen from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.8X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). Isopsoralen is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.7X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2019).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 102(SRC), determined from a log Kow of 2.08(2) and a regression-derived equation(3), indicates that isopsoralen is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 6.8X10-7 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 74 days and greater than 1 year, respectively(SRC). According to a classification scheme(5), an estimated BCF of 11(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2019).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), isopsoralen, which has an estimated vapor pressure of 9.7X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase isopsoralen is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 9 hours(SRC), calculated from its rate constant of 4.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Vapor-phase isopsoralen is degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 13 hours(SRC), calculated from its rate constant of 2.1X10-17 cu cm/molecule-sec at 25 °C(SRC) derived using a structure estimation method(2). Particulate-phase isopsoralen may be removed from the air by wet and dry deposition(SRC). Isopsoralen absorbs UV light at wavelengths of 299 nm(3) and, therefore, is expected to be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC).

The rate constant for the vapor-phase reaction of isopsoralen with photochemically-produced hydroxyl radicals has been estimated as 4.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 9 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of isopsoralen with ozone has been estimated as 2.1X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 13 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). The lactone ring in isopsoralen is susceptible to alkaline hydrolysis(3); therefore, isopsoralen may undergo hydrolysis under alkaline environmental conditions(SRC). Isopsoralen absorbs UV light at wavelengths of 299 nm(3) and, therefore, is expected to be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC).

An estimated BCF of 11 was calculated in fish for isopsoralen(SRC), using a log Kow of 2.08(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of isopsoralen is estimated as 102(SRC), using a log Kow of 2.08(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that isopsoralen is expected to have high mobility in soil.

The Henry's Law constant for isopsoralen is estimated as 6.8X10-7 atm-cu m/mole(SRC) developed using a fragment constant estimation method(1). This Henry's Law constant indicates that isopsoralen is expected to be essentially nonvolatile from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 74 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as greater than 1 year(SRC). Isopsoralen's Henry's Law constant indicates that volatilization from moist soil surfaces is not likely to occur(SRC). Isopsoralen is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.7X10-6 mm Hg(SRC), determined from a fragment constant method(1).

Occupational exposure to isopsoralen may occur through dermal contact with this compound at workplaces where isopsoralen is produced or used. Limited monitoring data indicate that the general population may be exposed to isopsoralen via ingestion of food and plants containing isopsoralen. Dermal exposure to isopsoralen occurs by direct medical treatment. (SRC)|Skin disorders appear to represent a widespread but largely unrecognized problem among supermarket employees. Many of the rashes among these workers appear to be phytophotodermatitis, a well-circumscribed rash evoked by contact with linear furanocoumarins (psoralens), followed by exposure of the skin to long-wave ultraviolet light (350 nm). It is associated with exposure to a wide variety of fruits, flowers, and vegetables, including celery, dill, parsley, oil from lime peels, parsnip, oil of Bergamot, and chrysanthemums. Exposure to sunlight is sufficient to provoke phytophotodermatitis following contact with psoralens. However, the use of artificial ultraviolet light in tanning salons appears in the present instance to have enhanced this effect. ... It is not possible at present to ascribe the etiology of this outbreak to any single foodstuff. However, since only workers who had contact with fresh produce developed rash, it appears likely that the psoralen-containing agent in the present outbreak is to be found among the vegetables, fruits, or flowers handled in this market. Surveillance of skin rashes in supermarket workers and investigation of additional outbreaks may help to identify a specific etiologic agent(1). /Psoralens/

/EXPL THER/ BACKGROUND: Modern studies have shown that psoralen has a significant inhibitory effect on tumor growth in a variety of animals and humans. OBJECTIVE: To obtain coumarin compounds - psoralen and isopsoralen - from traditional Chinese medicine Psoralea corylifolia L. using chromatographic techniques and isolation and purification methods, and to observe the transplanted tumor growth inhibitory effects and adverse reactions of psoralen and isopsoralen in nude rats with osteosarcoma. METHODS: Dried ripe fruits of Psoralea corylifolia L. were taken as the raw material to prepare crude extract of Psoralea corylifolia L. by ethanol reflux method. Column chromatography was used to isolate the crude extract; compounds were structurally identified based on (1)H-NMR, (13)C-NMR spectra, the two compounds were identified as psoralen andisopsoralen, and their contents were 99.7% and 99.6, respectively. Nude rat model of osteosarcoma was established; the rats were randomized into: normal saline group, psoralen low- and high-dose groups, isopsoralen low- and high-dose groups, and cisplatin group. Osteosarcoma volume and weight inhibition rates in nude rats in each group were observed; radioimmunoassay was used to determine the serum alkaline phosphatase activity; peripheral blood cell and bone marrow nucleated cell counts were determined; light microscopy was used to observe heart, liver, spleen, lung, kidney, and tumor histopathology; and electron microscopy was used to observe the fine structure of tumor cells. RESULTS: Tumor volume inhibition rates were 43.75% and 40.18%, respectively, in the psoralen and isopsoralen low-dose groups, and tumor weight inhibition rates were 38.83% and 37.77%. Tumor volume inhibition rates were 67.86% and 66.96%, respectively, in the psoralen and isopsoralen high-dose groups, and tumor weight inhibition rates were 49.47% and 47.87%. Psoralen and ispsoralen markedly lowered serum AKP level. Psoralen and isopsoralen induced apoptosis or necrosis of osteosarcoma. After administration of high doses of psoralen and isopsoralen, toxic reactions such as writhing, lassitude, and hypoactivity were seen. Kidney histopathology showed tubulointerstitial dilatation and congestion, and inflammatory cell aggregation in the renal intercellular space. Psoralen and isopsoralen did not cause any significant toxic side effects to the bone marrow, or other organs such as heart, lung, liver, and spleen. CONCLUSION: Psoralen and isopsoralen have growth inhibitory effects on transplanted tumor in nude rats with osteosarcoma, and can induce tumor cell apoptosis or necrosis, without significant toxic effects.|/EXPL THER/ Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 hr before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.|/EXPL THER/ Isopsoralen is a type of furocoumarin that exhibits estrogen-like activities. The aim of this study was to determine the estrogen-like neuroprotection of isopsoralen in an animal model of spinal cord injury (SCI). Results indicated that isopsoralen (intraperitoneal injection of 5 and 10 mg/kg per day for two weeks) significantly enhanced the hindlimb locomotor functions of mice with SCI, as revealed in the BMS score and angle of inclined plane tests. Morphological data showed that isopsoralen significantly attenuated the injury of the gray matter of spinal cord and induced the up-regulation of ERa levels. The neuroprotective effects of isopsolaren were blocked by the ERa antagonist MPP (0.3 mg/kg), but not by the ERbeta receptor antagonist PHTPP (0.3 mg/kg). Isopsolaren treatment increased phosphorylated PI3K and AKT (P-PI3K and P-AKT) in the spinal cord of SCI mice and showed a significant anti-apoptotic activity. These results suggest that isopsoralen performs estrogen-like neuroprotection against SCI-induced apoptosis by activating ERa and regulating the PI3K/AKT pathway.|/EXPL THER/ Previous studies have reported that angelicin exerted antiproliferative effects on several types of tumor cell. However, to the best of our knowledge, the effects of angelicin monotherapy on human liver cancer remain to be investigated. In the present study, the antitumor activity of angelicin was evaluated in vitro and in vivo, and the molecular mechanisms underlying its effects were investigated. The present results revealed that angelicin induced apoptosis in liver cancer cells in a dose- and time-dependent manner. Furthermore, in HepG2 and Huh-7 cells, angelicin-induced apoptosis was demonstrated to be mitochondria dependent, involving the phosphatidylinositol-4,5-bisphosphate 3-kinase/RAC-a serine/threonine-protein kinase signaling pathway. In addition, administration of angelicin to mice bearing liver tumor xenografts inhibited tumor growth, without producing significant secondary adverse effects. These results suggested that angelicin may have potential as a novel therapeutic agent for the treatment of patients with liver cancer.|/EXPL THER/ BACKGROUND: Angelicin is a furocoumarin found in Psoralea corylifolia L. fruit. The purpose of this study was to investigate the protective ability of angelicin against inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced in vivo acute lung injury model. MATERIALS AND METHODS: The concentrations of tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6 in the culture supernatants of RAW 264.7 cells were determined 24 hr after LPS administration. ALI was induced by intratracheal instillation of LPS. Six hours after LPS inhalation, bronchoalveolar lavage fluid and lung tissue samples were obtained for enzyme-linked immunosorbent assay, histologic, and Western blotting analyses. RESULTS: The results showed that pretreatment with angelicin markedly downregulated TNF-a and IL-6 levels in vitro and in vivo, and significantly decreased the amount of inflammatory cells, lung wet-to-dry weight ratio, and myeloperoxidase activity in LPS-induced ALI mice. Furthermore, Western blotting analysis results demonstrated that angelicin blocked the phosphorylation of IkappaBa, NF-kappaBp65, p38 MAPK, and JNK in LPS-induced ALI. CONCLUSIONS: These results suggest that angelicin was potentially advantageous to prevent inflammatory diseases by inhibiting NF-kappaB and MAPK pathways. Our data indicated that angelicin might be a potential new agent for prevention of inflammatory reactions and diseases in the clinic.

A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the ANTI-ANXIETY AGENTS (minor tranquilizers), ANTIMANIC AGENTS, and the ANTIPSYCHOTIC AGENTS (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. (See all compounds classified as Tranquilizing Agents.)|Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)|Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA. (See all compounds classified as Intercalating Agents.)

OBJECTIVE: To investigate the nasal absorption regularities of psoralen and isopsoralen of different concentrations. METHOD: Building an experimental model of rat in situ nasal recirculation and determining the contents of psoralen and isopsoralen by HPLC. RESULT: The nasal absorption of psoralen and isopsoralen fitted in with zero order kinetics, getting saturated with the increase of concentration. CONCLUSION: A suitable concentration is necessary for the preparation of nasal remedies psoralen and isopsoralen.|Coumarin components from Psoralea corylifolia L. are novel drugs in which psoralen and isopsoralen are the active components. The pharmacokinetics, tissue distribution and excretion of the two compounds were studied by liquid chromatography-tandem mass spectrometry after intravenous administration to Wistar rats. The elimination half-lives of psoralen and isopsoralen were 4.88 and 5.35 hr. After dosing, the area under the curves of the tissues decreased in the following order: liver > lung > heart > kidney > spleen > brain for psoralen; and kidney > lung > liver > heart > spleen > brain for isopsoralen. After dosing, 51.27% of psoralen and 56.25% of isopsoralen were excreted as prototype, and urine was the major excretion route. In addition, the pharmacokinetics of psoralen and isopsoralen after oral administration to Wistar rats were also studied. The elimination half-lives of psoralen and isopsoralen were 4.13 and 5.56 hr, and their relative bioavailabilities were 61.45% and 70.35%. Overall, the results show that coumarin components from P. corylifolia L. have high oral bioavailability, they are rapidly and widely distributed into tissues after intravenous administration, but they are slowly cleared and excreted

...The elimination half-lives of psoralen and isopsoralen /after iv administration to Wistar rats/ were 4.88 and 5.35 hr. ...The elimination half-lives of psoralen and isopsoralen /after oral administration to Wistar rats/ were 4.13 and 5.56 hr...

The combined action of 365 NM UV light & angelicin inhibited the injection of phage lambda into the host. The inhibition of injection is discussed in terms of photochemically induced crosslinking of the dna inside the phage heads. The electronic structures in the 1st excited states calculated by means of quantum chemistry according to the ppp method were very similar for xanthotoxin, psoralen, & angelicin.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ENDOCRINE MODULATION/ The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.|/GENOTOXICITY/ The transient nuclease sensitivity of repair patches during excision repair of UV or angelicin damage in T98g cells was independent of the initial distribution of DNA damage in chromatin. Repair patches produced in response to a linker-specific damaging agent became distributed randomly in chromatin, which suggested that nucleosome cores do not necessarily return to their original sites along a DNA strand after the DNA is repaired.|/GENOTOXICITY/ Photoactivated 8-methoxypsoralen (8-MOP) has been proven to be clinically effective for a number of dermatological conditions including lichen planus, mycosis fungoides, and psoriasis. 8-MOP forms two types of covalent photoproducts with DNA, monoadducts, and bifunctional adducts which cross-link the two DNA strands. Angelicin is a congener of 8-MOP which forms only monoadducts. We have used the combined density and isotopic labeling technique to study repair replication in cultured human fibroblasts treated with either of these compounds and exposed to near-ultraviolet light. In human diploid fibroblasts (WI-38), the time course of repair replication for both compounds is similar. Drug concentration and ultraviolet dose responses are also similar for 8-MOP and angelicin. No repair replication was stimulated by either compound in xeroderma pigmentosum cells from Complementation Group A (XP12BE). These results suggest that repair replication in response to 8-MOP is primarily a response to monoadducts and that the enzymatic pathway for this repair synthesis shares at least one step with the pathway for repair of pyrimidine dimers. Cross-link persistence in treated cells was assayed by use of the single-strand-specific S1 nuclease to digest DNA that did not renature readily following heat denaturation. Partial removal of cross-links was observed in normal, xeroderma pigmentosum variant, and Fanconi's anemia fibroblasts, but not in xeroderma pigmentosum Group A cells.|/GENOTOXICITY/ The comparative photosensitizing effects to near-UV irradiation (UVA) of several naturally occurring furocoumarins, 5-methoxypsoralen (5MOP), psoralen, 8-methoxypsoralen (8MOP) and angelicin in producing chromosome damage in vitro in cells derived from hamster, normal human, ataxia telangiectasia (AT) and xeroderma pigmentosum (XP) patients were studied. In Chinese hamster cells, lethality was greatest with psoralen and least with angelicin; 8MOP and 5MOP were intermediate. 8MOP and 5MOP produced sister-chromatid exchanges with almost equal efficiency and to a larger extent by far than angelicin. In all human cell lines studied, 8MOP and 5MOP were similarly effective in the production of sister-chromatid exchanges and chromosomal aberrations. AT and XP cells responded with higher frequencies of sister-chromatid exchanges as well as chromosomal aberrations than normal human cells to 5MOP, 8MOP and angelicin. Evidence is presented which suggests that cell death in Chinese hamster cells following angelicin photosensitization is not clearly related to the production of sister-chromatid exchanges. AT cells were unexpectedly more sensitive to angelicin than normal cells. The presence of 5MOP in some sun-tan preparations is not acceptable in view of the present evidence of its biological activity.|For more Human Toxicity Excerpts (Complete) data for Isopsoralen (10 total), please visit the HSDB record page.

angelicin

Psoralens are natural furocoumarins well-known for their photosensitizing potential. Porphyrins, including hematoporphyrin derivatives (HPD), are also potent photosensitizers. ... Psoralens ... have an action spectrum in the UV-A range. /Psoralens/

Psoralea corylifolia leaves were dried, pulverized, extracted with ether, & the extract treated with 5% sodium carbonate & then with 5% sodium hydroxide to give an aqueous fraction, which was neutralized in 10% sulfuric acid, & extracted with chloroform. The original phase was evaported, dissolved in petroleum ether & crystallized to give crystalline psoralen & angelicin.|TLC on silufol LIV-254 plates with a luminescent indicator was used for the separation of psoralen & angelicin. The solvent system was petroleum ether-ethyl acetate (2:1). The furocoumarins were eluted from silufol by heating with 95% alcohol for 3 hr & determined by spectrophotometric analysis of the eluate at 246 nm. The spectrophotometric analysis limit for angelicin was 0.6 ug.|Furocoumarins from different parts of heracleum laciniatum were separated by TLC & indirectly quantified by fluorospectrophotometry. Benzene/ether (2.5:1) gave the best separation on silica gel plates. Bergapten, pimpinellin, angelicin, sphondin, isobergapten, & isopimpinellin were identified. The contents of furocoumarins in the extracts from roots & leaves were approx equal & slightly higher than that of fruits. The stems contained only small amounts.|A colorimetric method based on a diazotizing reaction for psoralen & isopsoralen (angelicin), alone, in mixtures, & in tablet dosage forms.