| Objective:To isolate the chemical constituents and screen the anti-oxidative and antineoplastic compounds from Psoralea corylifolia L. seeds; clarify the main components in the plasm from rats after oral administration of Psoralea corylifolia water extract; Study the drug metabolism process of isobavachalcone in rats.Methods:1. The methanol extract and 70% ethyl alcoho extract of Psoralea corylifolia were separated by a variety of column chromatography and the modern separation methods, the compounds were identified by nuclear magnetic resonance(NMR) and Eleetros Pray Ionization Mass Spectrogram(ESI-MS). 2. ABTS(2, 2- al nitrogen base- double-(3- ethyl benzothiazole Lin- 6- sulfonic acid) ammonium salt) and DPPH(1, 1-diphenyl-2- picrylhydrazyl) method were used to detect antioxidant activity, and determined by MTT(methyl thiazolyl tetrazolium) method to evaluate the antitumor activity of against two human hepatoma cells Hep G2 and human breast MDA-MB-231 cell lines. 3. A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was developed for detecting the main components in the serum of rats after oral administration of Psoralea corylifolia water extract and compared with the reference substance. 4. A simple and selective specific LC-MS/MS method for determination of isobavachalcone(IBC) in rat plasma was developed. This method was suitable for pharmacokinetic studies after oral administration of 80 mg/kg IBC in rats. Blood samples were collected from the vein after IBC administration, the plasma drug concentration in each time point was detected by the LC-MS/MS method and established mean plasma concentration-time profiles. The relevant pharmacokinetic parameters were calculated using DAS software. Results:1. Eighteen compounds were obtained and identified as phenylpropanoids: psoralen(1), isopsoralen(2), psoralidin(3), psoralenoside(4), isopsoralenoside(5); monoterpene phenols: bisbakuchiols A(6), bisbakuchiols B(7), bakuchiol(8), 13-hydroxyisobakuchiol(9),12,13-dihydro-12,13-epoxybabakuchiol(10); Flavonoids: isobavachlcone(11), bavachromene(12), corylinin(13), neobavaisoflavone(14), corylin(15), bavachin(16), isobavachin(17), bavachinin(18). 2. Compounds 3,6,7,12 shown scavenging effect to the DPPH radical; Compounds 8 ~ 9,11 ~ 14,16 shown scavenging effect to the ABTS radical; Compounds 3,8 ~ 9,11 ~ 18 displayed the antiproliferation effect to the Human hepatoma cells Hep G2 and Human breast cancer cells MDA-MB-231, Compounds 7 displayed the antiproliferatio effect to the Human hepatoma cells Hep G2. 3. Compounds 1, 2, 3, 4, 11 ~ 14, 16 ~ 18 were the main ingredients in rat plasm. 4. The drug metabolizing process of Isobavachalcone in rats fit a two-compartment model; the main pharmacokinetic parameters are listed as follows, peak time(Tmax): 2.25 ± 0.52 h, maximum plasma concentration(Cmax): 351.2 ± 229.2 ng/m L, half-life(T 1/2): 6.15 ± 1.99 h, The area under the plasma concentration–time curve(AUC(0–∞)): 1665.5 ± 270.9 ng/m L · h, plasma clearance(CL/F): 9.86 ± 1.78 L/h, apparent volume of distribution(V/F): 90.34 ± 47.17 L.Conclusions:1. Eighteen compounds were obtained from Psoralea corylifolia. Psoralidin, Bisbakuchiols A, Bisbakuchiols B, Bakuchiol, 13-hydroxyisobakuchiol, Isobavachlcone, Bavachromene, Corylinin, Neobavaisoflavone and Bavachin were endowed with antioxidant activity; Psoralidin, Bakuchiol, 13-hydroxyisobakuchiol, Isobavachlcone, Bavachromene, Corylinin, Neobavaisoflavone, Corylin, Bavachin, Isobavachin and Bavachinin were endowed with Antitumor activity. 2. The main ingredients in rat plasm were psoralen, isopsoralen, psoralenoside, isopsoralenoside, isobavachlcone, bavachromene, corylinin, neobavaisoflavone, bavachin, isobavachin, bavachinin. 3. The LC-MS/MS method was suitable for pharmacokinetic studies after oral administration of 80 mg/kg IBC in rats. We also obtained pharmacokinetic parameters and concentration-time profiles for IBC after oral administration of IBC in rats. |
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