Pimpinellin

246.21

246.22

D419UK1B4L

DTXSID20156831

Off-white needles from methylene chloride/hexane|Yellowish needles

2932999099

57.9

2.06

1.352±0.06 g/cm3(Predicted)

119 °C

441.0±45.0 °C(Predicted)

220.5±28.7 °C

1.612

In water, 647 mg/L at 25 °C (est)

1.20X10-6 mm Hg at 25 °C (est)

Henry's Law constant = 2.37X10-9 atm-cu m/mol at 25 °C (est)

146.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 2.13X10-10 cu cm/molec-sec at 25 °C (est)

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.

|Danger|H301 (50%): Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P271, P272, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P310, P311, P312, P321, P322, P330, P333+P313, P361, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

IDENTIFICATION AND USE: Pimpinellin is a component of Angelica dahurica roots which is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation. HUMAN STUDIES: Photoepicutaneous testing showed phototoxic effects from pimpinellin. Action spectrum studies demonstrated peak photosensitivity in the range 330-335 nm. It inhibited growth of human carcinoma cells. Moreover, pimpinellin inhibited the growth of tumor cells via the induction of tumor cell apoptosis. ANIMAL STUDIES: Pimpinellin was phototoxic the in vitro Candida test.

Investigations on light reactions in a patient with vitiligo are presented. The minimal erythema dose (MED) in the UVB area was approximately 1/3 of that in persons of skin type II. The application of furocoumarins (psoralens) increased light tolerance by 1 MED at 300-310 nm. Action spectrum studies with furocoumarins from Heracleum laciniatum showed the following order of potency: bergapten, pimpinellin, angelicin and sphondin. The efficacy was highest at 325-350 nm, with maxima at 330-335 nm. Pimpinellin was recently found to be phototoxic, but an action spectrum of sphondin is reported for the first time.

Pimpinellin is a compound found in many plants, including those from the Apiaceae and Rutaceae families(1). It is reported in Pimpinella saxifraga L., Heracleum spondylium L., H. lanatum, H. panaces L., Umbelliferae(2).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 320(SRC), determined from a structure estimation method(2), indicates that pimpinellin is expected to have moderate mobility in soil(SRC). Volatilization of pimpinellin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.4X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Pimpinellin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2019).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 320(SRC), determined from a structure estimation method(2), indicates that pimpinellin is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.4X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Pimpinellin is expected to undergo hydrolysis in the environment due to the presence of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(4), an estimated BCF of 6(SRC), from an estimated log Kow of 1.70(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. 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), pimpinellin, which has an estimated vapor pressure of 1.2X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase pimpinellin 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 2 hours(SRC), calculated from its rate constant of 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). The rate constant for the vapor-phase reaction of pimpinellin 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(2). This corresponds to an atmospheric half-life of about 13 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(3). Particulate-phase pimpinellin may be removed from the air by wet and dry deposition(SRC). Pimpinellin contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of pimpinellin with photochemically-produced hydroxyl radicals has been estimated as 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of pimpinellin 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 analogous isopsoralen is susceptible to alkaline hydrolysis(3); therefore, pimpinellin may undergo hydrolysis under alkaline environmental conditions(SRC). Pimpinellin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 6 was calculated in fish for pimpinellin(SRC), using an estimated log Kow of 1.70(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of pimpinellin can be estimated to be 320(SRC). According to a classification scheme(2), this estimated Koc value suggests that pimpinellin is expected to have moderate mobility in soil(SRC).

The Henry's Law constant for pimpinellin is estimated as 2.4X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that pimpinellin is expected to be essentially nonvolatile from water and moist soil surfaces(2). Pimpinellin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-6 mm Hg(SRC), determined from a fragment constant method(1).

Occupational exposure may be limited to dermal exposure where plants that contain pimpinellin are harvested or processed. The general public is not likely to be exposed to pimpinellin unless by dietary supplement or direct medical treatment. (SRC)

/EXPL THER/ The presented work reports anticholinesterase and antioxidant activities of extracts, fractions from aerial parts, fruits, flowers, roots and isolated compounds of roots from Leiotulus dasyanthus (bergapten, pimpinellin, umbelliferone, quercetin, rutin and kaempferol). Phenolic contents, antioxidant activities of samples were carried out by Folin-Ciocalteu, DPPH, TBA methods. Anticholinesterase activity was evaluated by Ellman's method. The highest and lowest total phenolic content were detected in root MeOH extract (88.6 mg GAE/g DW) and aerial part (51.83 mg GAE/g DW), respectively. The highest antioxidant activity among isolated secondary metabolites got coumarins umbelliferone, bergapten and pimpinellin. Pimpinellin (66.55%) and umbelliferone (61.09%) demonstrated strong inhibition towards acetylcholinesterase and butyrylcholinesterase, respectively. Dichloromethane fraction of root demonstrated significant inhibition against AChE (49.66%) and BuChE (92.21%) at 20 ug/mL. Dichloromethane fractions of roots had a notableness antioxidant and anticholinesterase activities. The further studies on roots will be important for development use of this plant for pharmaceutical and food research needs.

/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/

/HUMAN EXPOSURE STUDIES/ Isolation of the furocoumarins (psoralens) bergapten, isobergapten, sphondin, isopimpinellin and pimpinellin from the Umbilliferous plant Heracleum laciniatum was carried out by column chromatography, and the structure and absorption spectra for the 5 furocoumarins isolated are described. Photoepicutaneous testing showed the strongest phototoxic effects from bergapten, marked effects from pimpinellin, weak effects from sphondin and none from the others. These in vivo findings were confirmed by the in vitro Candida test. Action spectrum studies demonstrated peak photosensitivity in the range 330-335 nm, bergapten being more than twice as phototoxic as pimpinellin.|/ALTERNATIVE and IN VITRO TESTS/ BACKGROUND: Cyrtomium fortumei (J.) Smith is an important Chinese herbal medicine because of its biological functions. However, systematic and comprehensive studies on the phytochemicals from Cyrtomium fortumei (J.) Smith and their bioactivity are limited. RESULTS: Using the bioassay-guided technique, the ethyl acetate and n-BuOH extracts of the rhizomes of Cyrtomium fortumei (J.) Smith were shown to exhibit good antitumor activities, consequently leading to the isolation of 23 compounds. All compounds were isolated from the plant for the first time. The inhibitory activities of these compounds were investigated on tumor cells MGC-803, PC3, and A375 in vitro by MTT (thiazolyl blue tetrazolium bromide) assay, and the results showed that pimpinellin (3) had potent cytotoxic activities against the three cell lines, with the IC50 values of 14.4 +/- 0.3 uM, 20.4 +/- 0.5 uM, and 29.2 +/- 0.6 uM, respectively. The mechanism of the antitumor action indicated that pimpinellin inhibited the growth of MGC-803 cells via the induction of tumor cell apoptosis, with apoptosis ratio of 27.44% after 72 hr of treatment at 20 uM. CONCLUSIONS: This study suggests that most of the compounds from the roots of Cyrtomium fortumei (J.) Smith could inhibit the growth of human carcinoma cells. Moreover, pimpinellin inhibited the growth of tumor cells via the induction of tumor cell apoptosis.

pimpinellin

Pimpinellin is a component of Angelica dahurica roots which is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation.|Pimpinellin was found in Yuanhu Zhitong tablet (Chinese medicine)

A method of microwave-assisted extraction coupled with high-speed counter-current chromatography was established for separation and purification of isopimpinellin, pimpinellin and phellopterin from Toddalia asiatica (L.) Lam. The conditions of MAE including the extraction solvent, size of sample, solid/liquid ratio, extraction temperature and extraction time were optimized by a mono-factor test. That is, 2.0 g dried powder of T. asiatica (L.) Lam of 0.30-0.15 mm size was extracted with 20 mL (solid/liquid ratio of 1:10, g/mL) methanol under 50 °C for 1 min. The crude extract was separated and purified by high-speed counter-current chromatography with hexane-ethyl acetate-methanol-water (5:5:5.5:4.5, v/v/v/v) solvent system. 0.85 mg/g of isopimpinellin, 2.55 mg/g of pimpinellin and 0.95 mg/g of phellopterin were obtained from original sample in one-step within 240 min, the purity determined by high performance liquid chromatography was 95.0%, 99.1% and 96.4%, respectively. Their chemical structures were further identified by mass spectroscopy and nuclear magnetic resonance spectroscopy. The results demonstrated that microwave-assisted extraction coupled with high-speed counter-current chromatography was a feasible, economical and efficient technique for rapid extraction, separation and purification of effective compounds from natural products.|A reversed-phase HPLC method with atmospheric pressure chemical ionisation MS detection has been developed for the separation and identification of coumarins in plants of Peucedanum palustre L. (Moench) and Angelica archangelica (L.) var. archangelica. The Turbo Method Development program was utilised to optimise the mobile phase with two organic solvents (acetonitrile and methanol) and two aqueous solutions (1.0% formic acid and 10 mM ammonium acetate). Optimisation of the solvent gradients for the method was performed with the aid of the DryLab program. Analyses were carried out using a Phenomenex Prodigy RP C18 column. Fifty-two peaks (14 of which were associated with coumarins) were separated in 30 min from extracts of P. palustre, and 48 peaks (15 associated with coumarins) from extracts of A. archangelica. A total of 21 different coumarin-type compounds were identified in the aerial and the underground parts of the title plants. Isopimpinellin and pimpinellin were found for the first time in P. palustre and were identified by comparison of retention times and MS data obtained following the analysis of pure standards. This is the first report of the coumarin composition of the umbels of P. palustre.|A simple, rapid, and sensitive HPLC-UV method was developed for qualitative and quantitative analysis of 12 coumarin compounds (skimin, scopolin, scopoletin, umbelliferone, 6,7-dimethoxycoumarin, coumarin, psoralen, xanthotoxin, 5,7-dimethoxycoumarin, pimpinellin, imperatorin, and osthole) in bamboo leaves. The samples were extracted with ethanol-water (70 + 30, v/v) by ultrasonication and purified by Florisil SPE. The method was validated for linearity, LOD, LOQ, accuracy, precision, and recovery. The standard curves in the corresponding ranges had good linearity. LOD was at the range of 0.19 to 0.85 mg/kg and LOQ 0.64 to 2.82 mg/kg. The values of RSD for accuracy and intraday and interday precision were less than 3%, except for 6,7-dimethoxycoumarin. Recoveries from spiked samples at 30, 20, and 10 mg/kg in Dendrocalamus giganteus Munro were higher than 70%, except for scopoletin, 6,7-dimethoxycoumarin, and coumarin. The method was validated using field-collected samples taken from Beijing and Changning Counties, SiChuan, China. Six coumarins, namely, skimin, scopolin, scopoletin, umbelliferone, coumarin, and pimpinellin, were found in the extracts of 11 species of bamboo leaves. The concentrations of total coumarins were in the range of 8.67 to 99.2 mg/kg. The maximum concentration of total coumarins was found in Bambusa pervariabilis, and the minimum was in.|A rapid resolution liquid chromatography coupled with a triple quadrupole mass spectrometry (RRLC-QQQ) was employed to identify and quantify the major bioactive constituents in Yuanhu Zhitong tablet (YZT), a traditional Chinese medicine. Seventeen constituents were simultaneously determined and quantified by reference standards in 9 min, namely scopoletin, protopine, alpha-allocryptopine, tetrahydropalmatine, coptisine, tetrahydroberberine, corydaline, berberine, byakangelicin, byakangelicol, xanthotoxin, bergapten, pimpinellin, oxypeucedanin, imperatorin, osthole and isoimperatorin. All of them were performed on an Agilent XDB C(18) column (4.6 mm x 50 mm, 1.8 um) with linear gradient elution of acetonitrile-0.3% formic acid water (pH 2.7). The proposed method was applied to analyze 15 batches of samples with acceptable linearity (r(2), 0.9938-0.9999), precisions (RSD, 1.01-4.92%), repeatability (RSD, 1.33-4.91%), stability (RSD, 1.46-4.86%), recovery (RSD, 1.11-4.81%) of the seventeen compounds. Furthermore, the Hierarchical Cluster Analysis was applied to classify 15 samples based on characteristics of the 17 compound markers. As a result, the analytical method possessing high sensitivity and speed is suitable for the quality control of YZT.

A rapid and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for simultaneous determination of three bioactive coumarins of Toddalia asiatica extract including pimpinellin, isopimpinellin and phellopterin in rat plasma for the first time. Phenacetin was used as the internal standard (IS). Plasma samples were extracted by liquid-liquid extraction with methyl tert-butyl ether. The chromatographic separation was carried out on an ACQUITY UPLC BEH C18 column with an isocratic mobile phase consisting of methanol-5 mmol/L ammonium acetate (65:35, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with positive ionization mode. The method was linear for all analytes over investigated range with all correlation coefficients greater than 0.9942. The lower limits of quantification (LLOQ) were 25.0 ng/mL for pimpinellin, 10.0 ng/mL for isopimpinellin and 5.00 ng/mL for phellopterin. The intra- and inter-day precision (RSD%) was within 12% and the accuracy (RE%) ranged from -2.3% to 5.5%. The rapid and sensitive method was fully validated and successfully applied to the pharmacokinetic study of pimpinellin, isopimpinellin and phellopterin in rats following oral administration of Toddalia asiatica extract.