periplocymarin and periplogenin

A sensitive and specific ultra-performance liquid chromatographic-tandem mass spectrometric method was developed and validated to simultaneously determine periplocin, periplocymarin (PM), periplogenin (PG), periplocoside M (PSM) and periplocoside N (PSN) in rat plasma. Acetonitrile was employed to precipitate plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a Waters HSS T3 column with a gradient elution using water and acetonitrile both containing 0.1% formic acid and 0.1 mm ammonium formate within 8 min. Detection was performed in positive ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. Using this method, the concentrations of periplocin, PM, PG, PSM and PSN were established after oral administration of Cortex Periplocae extract to rats, and the pharmacokinetic characteristics of periplocin, PM, PG, PSM and PSN were assessed. Generally, PM, PG, PSM and PSN were eliminated slowly and their half-lives were all >8 h. In addition, the systemic exposure of PSM showed significant differences between genders with more than 10 times higher area under the concentration-time curve in female rats than in male rats. The findings of this study provide useful information for further research on Cortex Periplocae.

Topics: Administration, Oral; Animals; Cardiac Glycosides; Chromatography, High Pressure Liquid; Digitoxigenin; Female; Male; Rats; Reproducibility of Results; Saponins; Tandem Mass Spectrometry

During a screening of Chinese plants traditionally used for the treatment of cancer and related diseases, extracts of the root bark of Periploca sepium Bunge showed strong cytotoxic activity.. Isolate and identify cytotoxic compounds from P. sepium and investigate the effects and mechanism of action on different cancer cell lines.. Extracts obtained with solvents of different polarities of the root bark of P. sepium were tested for their anti-proliferative effects. The most active extract was subjected to activity-guided fractionation using different chromatographic methods. The most active compound was further investigated on sarcoma cell lines regarding its effects concerning apoptosis, DNA damage and death receptor expression.. We isolated the cardiac glycosides periplocin, glucosyl divostroside, periplogenin, periplocymarin and periplocoside M with periplocin exhibiting the lowest IC. Periplocin displays a promising mechanism of action in sarcoma cells because altering the death receptor expression is an interesting target in sarcoma treatment especially to overcome TRAIL resistance.

Topics: Apoptosis; Cardiac Glycosides; Cell Line, Tumor; China; Digitoxigenin; Humans; Liposarcoma; Periploca; Plant Extracts; Plant Roots; Plants, Medicinal; Receptors, Death Domain; Saponins

Periplocin is a cardiac glycoside and has been used widely in the clinic for its cardiotonic, anti-inflammatory and anti-tumor effects. Although it is taken frequently by oral administration in the clinic, there have been no reports demonstrating that periplocin could be detected in vivo after an oral administration, so there is an urgen need to determine the characteristics of periplocin in vivo after oral administration. In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed and validated to identify and quantify periplocin and its two metabolites in rat tissue after a single dosage of perplocin at 50 mg/kg. The results demonstrated that periplocin and its two metabolites were detected in all of the selected tissues; periplocin could reach peak concentration quickly after administration, while periplocymarin and periplogenin reached maximum concentration > 4.83 h after administration. The tissue distribution of analytes tended to be mostly in the liver, and higher analyte concentrations were found in the heart, liver, spleen, lung and kidney, but a small amount of chemical constituents was distributed into the brain. The consequences obtained using this method might provide a meaningful insight for clinical investigations and applications.

Topics: Animals; Cardiac Glycosides; Chromatography, Liquid; Digitoxigenin; Linear Models; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Saponins; Sensitivity and Specificity; Tandem Mass Spectrometry; Tissue Distribution

A sensitive and reliable LC-MS/MS method was developed and validated for the simultaneous determination of periplocin and its two metabolites (periplocymarin and periplogenin) in rat plasma using psoralen as the internal standard (IS). After liquid-liquid extraction with ethyl acetate, chromatographic separation was performed on a C18 column with a 13 min gradient elution using 0.1% formic acid and acetonitrile as mobile phase at a flow rate of 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer via an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in the positive ionization mode. The lower limits of quantitation (LLOQs) for periplocin, periplocymarin and periplogenin were 0.5, 1 and 0.1 ng/mL, respectively. The mean recoveries of the analytes and IS were higher than 67.7%. The proposed method was successfully applied to evaluating the pharmacokinetic studies of periplocin and its metabolites (periplocymarin and periplogenin) in rats after a single oral administration of periplocin at 50 mg/kg.

Topics: Acetonitriles; Administration, Oral; Animals; Calibration; Cardiac Glycosides; Chromatography, Liquid; Digitoxigenin; Formates; Limit of Detection; Male; Plasma; Quality Control; Rats; Rats, Sprague-Dawley; Saponins; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry