isopsoralenoside and psoralenoside

Absorption is crucial to the resultant efficacy of oral drugs where the intestinal bacteria flora functions as one of the first-pass effects.The present study investigated the biotransformation of psoralenoside and isopsoralenoside in Chinese medicine Psoraleae Fructus(the dried fruit of Psoralea corylifolia) with the internationally recognized human intestinal bacteria flora model in vitro.Pso-ralenoside and isopsoralenoside were anaerobically incubated with human intestinal bacteria flora at 37 ℃, respectively, and biotransformation products were analyzed and identified using high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS) and comparison with reference standards.The main biotransformation products of psoralenoside were psoralen and a small amount of 6,7-furano-hydrocoumaric acid, and the main biotransformation products of isopsoralenoside were isopsoralen and a small amount of 5,6-furano-hydrocoumaric acid.

Topics: Bacteria; Benzofurans; Biotransformation; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Fruit; Glycosides; Humans; Psoralea

Coumarins are the main active components in Psoraleae Fructus. To study the multi-component pharmacokinetics of Psoraleae Fructus, this study established a sensitive and rapid ultra-pressure liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of psoralen, isopsoralen, psoralenoside, and isopsoralenoside in rat plasma. After validation, the method was applied to the investigation of pharmacokinetics of psoralen, isopsoralen, psoralenoside, and isopso-ralenoside in rats after single and multiple administration of Psoraleae Fructus extract. The results revealed that the exposure of psoralen and isopsoralen in rat plasma was high after a single intragastric administration of Psoraleae Fructus extract, with an AUC_(0-∞) of 443 619-582 680 and 167 314-276 903 ng·mL~(-1)·h~(-1), respectively. Compared with these two compounds, the exposure of psoralenoside and isopsoralenoside was lower with marked gender difference. After 7-day administration of Psoraleae Fructus extract to rats, the AUC_(0-∞) of psoralen and isopsoralen was 29 701-81 783 and 39 234-89 914 ng·mL~(-1)·h~(-1), respectively, which was significantly lower than that at the first day(P<0.05), and that of psoralenoside and isopsoralenoside was 7 360-19 342 and 8 823-45 501 ng·mL~(-1)·h~(-1), respectively. There was no significant gender difference in exposure of psoralenoside and isopsoralenoside in male and female rats. However, the exposure of psoralenoside and isopsoralenoside in male rats was reduced(P<0.05), and the t_(1/2) and mean residence time(MRT) were shortened, suggesting that the removal of these two compounds from the body was accelerated.

Topics: Administration, Oral; Animals; Benzofurans; Chromatography, High Pressure Liquid; Chromatography, Liquid; Drugs, Chinese Herbal; Ficusin; Furocoumarins; Glycosides; Psoralea; Rats; Tandem Mass Spectrometry

Fructus Psoraleae, a traditional Chinese medicine, is widely used for preventing and treating various diseases such as vitiligo, osteoporosis and psoriasis. Coumarin, such as psoralenoside, isopsoralenoside, psoralen and isopsoralen, are important compounds in Fructus Psoraleae. In our study, ultra performance liquid chromatography coupled with diode array detector was employed for an excellent method validation for simultaneous quantification of psoralenoside, isopsoralenoside, psoralen and isopsoralen, which was further applied in performing general survey of Fructus Psoraleae from the different origins and chemical identification of the roasted from raw Fructus Psoraleae in the light of illuminating the transformed rule of psoralenoside and isopsoralenoside. There is a reciprocal relationship between (iso)psoralenoside and (iso)psoralen, and the total content remains balance in Fructus Psoraleae from the different origins. In addition, we found that (iso)psoralenoside in the powder of the raw Fructus Psoraleae could be easily transformed into (iso)psoralen in methanol aqueous solution, especially above 50% water, rather than the roasted one. Thus, we proposed a hypothesis that transformation between (iso)psoralenoside and (iso)psoralen was hindered by inactivation of β-glucosidase in the process of roasting Fructus Psoraleae, which was further verified by observing transformation of (iso)psoralenoside under the different conditions, such as temperature, pH and β-glucosidase. Therefore, we developed a feasible method to distinguish the roasted from raw Fructus Psoraleae by observing conversion from (iso)psoralenoside to (iso)psoralen in 50% methanol aqueous solution. In summary, these results pave the way for elevating quality standard for Fructus Psoraleae and distinguishing the salt-processed from raw Fructus Psoraleae.

Topics: Benzofurans; China; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Fruit; Glycosides; Medicine, Chinese Traditional; Psoralea

The dried fruit of Psoralea corylifolia L. has been used to prevent and treat vitiligo, osteoporosis, arthralgia and asthma in Traditional Chinese Medicine for some 1600 years. Psoralen (P), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) are the major coumarins and coumarin-related benzofuran glycosides in Psoraleae Fructus, which have been reported to show estrogen-like activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. The first aim of this study is to develop a rapid, sensitive and selective ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) approach for simultaneous determination of PO, IPO, P and IP in rat plasma and samples collected from in vitro incubation experiments. The second aim is to investigate the pharmacokinetic properties of PO, IPO, P and IP after oral administration of Psoralea corylifolia extract (PCE) to rats. The third aim is to confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions.. A UPLC-MS/MS method with a C18 column and a mobile phase of methanol-0.1% aqueous formic acid was validated according to the criteria in FDA guidelines about bioanalytical method, which was developed to investigate the pharmacokinetic behavior of PO, IPO, P and IP from PCE and the metabolic pathways of PO to P or IPO to IP.. The criteria for establishment of a new UPLC-MS/MS method including selectivity, linearity, accuracy, precision, extraction recovery, matrix effect and stability were validated. This method was successfully applied to the quantitative determination of PO, IPO, P and IP in biological samples collected from both in vitro incubations and in vivo rat experiments. After oral administration of PCE to rat, pharmacokinetic parameters of these four compounds indicated that in vivo biotransformation may occur between PO and P or IPO and IP. Purified benzofuran glycosides fraction (PBGF), containing only PO and IPO, was orally administered to rats to further confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. An in vitro incubation study elucidated that PO and IPO were metabolized to P and IP by intestinal microflora through de-glucosylation.. This paper developed a rapid, sensitive and selective UPLC-MS/MS method for simultaneous determination of PO, IPO, P and IP from PCE in biological samples, and investigated on their comprehensive in vivo and in vitro pharmacokinetic studies. These obtained results showed that the metabolism by intestinal bacteria plays an important role in pharmacological effects of orally administered PCE.

Topics: Animals; Benzofurans; Chromatography, Liquid; Ficusin; Fruit; Furocoumarins; Glycosides; Male; Molecular Structure; Plant Extracts; Psoralea; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Fructus Psoraleae, a widely used traditional Chinese medicine, is well known as a health supplement ingredient. In our study, an improved and comprehensive HPLC fingerprint of Fructus Psoraleae was established. Two important new benzofuran glycosides, psoralenoside and isopsoralenoside, were identified as characteristic constituents for the first time. HPLC separation was performed on an RP-C8 column. The mobile phase was acetonitrile and 0.1% acetic acid solution with linear gradient change of acetonitrile from 10 to 82% in 40 min. The flow rate was 1.0 mL/min, and the detection wavelength was set at 310 nm. The HPLC chromatograms of twenty-six samples from different regions of China showed a similar pattern. Twelve peaks were selected as characteristic peaks and further identified as psoralenoside, isopsoralenoside, psoralen, isopsoralen, bavachromene, corylifolin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, and bakuchiol, respectively. Nine of them were simultaneously quantitatively analyzed for the first time. A more comprehensive analytical method was established for the fingerprint of Fructus Psoraleae. It is very useful for authentication and quality assessment of the crude drug.

Topics: Benzofurans; Chalcones; Chromatography, High Pressure Liquid; Coumarins; Drugs, Chinese Herbal; Ficusin; Flavonoids; Fruit; Furocoumarins; Glycosides; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Phenols; Psoralea; Solvents

Two new benzofuran glycosides, called psoralenoside and isopsoralenoside, were isolated from the fruits of Psoralea corylifolia, together with nine known compounds. Their structures were elucidated by detailed spectral analyses including extensive two dimensional (2D) NMR spectra.

Topics: Benzofurans; Fruit; Glycosides; Hydrolysis; Light; Magnetic Resonance Spectroscopy; Plant Extracts; Psoralea; Scattering, Radiation; Spectrometry, Mass, Electrospray Ionization