RESUMEN
Gardeniae Fructus (GF) and Semen Sojae Praeparatum (SSP) are both medicine food homologies and widely used in Chinese clinical prescriptions together. The research investigated the pharmacokinetics of four iridoids in normal rats and isolfavones-fed rats, which were administered with isolfavones from SSP for 7, 14, 21 and 28 consecutive days. A validated LC-MS/MS method was developed for determining shanzhiside, genipin-1-gentiobioside, geniposide and their metabolite genipin in rat plasma. Plasma samples were pretreated by solid-phase extraction using paeoniflorin as the internal standard. The chromatographic separation was performed on a Waters Atlantis T3 (4.6 mm × 150 mm, 3μm) column using a gradient mobile phase consisting of acetonitril and water (containing 0.06％acetic acid). The mass detection was under the multiple reaction monitoring (MRM) mode via polarity switching between negative and positive ionization modes. The calibration curves exhibited good linearity (r>0.997) for all components. The lower limit of quantitation was in the range of 1-10 ng/mL. The intra-day and inter-day precisions (RSD) at three different levels were both less than 12.2％ and the accuracies (RE) ranged from -10.1％ to 16.4％. The extraction recovery of them ranged from 53.8％ to 99.7％. Pharmacokinetic results indicated the bioavailability of three iridoid glycosides and the metabolite, genipin in normal rats was higher than that in rats exposed to isoflavones. With the longer time of administration of iso-flavones, plasma concentrations of iridoids decreased, while genipin sulfate, the phase II metabolite of genposide and genipin-1-gentiobioside, appeared the rising exposure. The pharmacokinetic profiles of main iridoids from GF were altered by isoflavones.
RESUMEN
Objective:To observe the effect of Notch signal inhibitor DAPT (γ-secretase inhibitor ) on the pathological changes of atherosclerosis mice and the immune balance of Treg/Th17.Methods:24 ApoE knockout C57BL mice were randomly divided into blank group,model group and DAPT group.The blank group were fed with normal diet ,the model group and the experimental group were fed with high fat diet.After 5 weeks of feeding,the mice in the experimental group were injected with DAPT [100 mg/(kg· d),re-suspended in DMSO],and the other two groups were injected with the equivalent amount of DMSO .After another 5 weeks,pathological changes of the mice in each group were analyzed by HE staining .ELISA was used to detect the level of IL-17 in plasma,and the propor-tion of splenic Treg/Th17 cells in each group was detected by flow cytometry .Results:HE staining results showed that the model group had obvious plaque formation and foam cell formation ,which showed that the AS model was successfully prepared .The degree of arterial disease in the DAPT group was significantly less than that in the model group .The plasma levels of IL-17 in the blank group , model group and DAPT group were(293.94±28.59),(454.05±172.68) and (335.40±89.57) pg/ml,respectively .The percentages of Treg cells in the blank group,model group and DAPT group were(3.80±0.56)%,(2.54±0.38)%and(4.73±0.64)%,respective-ly.The Th17 cell subsets of mice in the blank group , model group and DAPT group were ( 3.46 ±0.23 )%, ( 4.52 ±0.85 )% and (1.38±0.37)%,respectively .Conclusion:DAPT decreased the plasma level of IL-17 in AS mice,inhibited the differentiation of Th17 cell subsets,and promoted the differentiation of Treg ,and reduced the atherosclerosis by changing the Treg/Th17 cells immune balance.