Effect of kaempferol on the pharmacokinetics of nifedipine in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of kaempferol on the pharmacokinetics of nifedipine (NFP) in rats.</p><p><b>METHODS</b>Twenty male SD rats, weighing 220-260 g, were distributed randomly into 4 groups. The animals were fasted, but allowed free access to water for 12 h before the administration of drugs. NFP dissolved in corn oil was administered via gastric intubation to the rats in control group at a dose of 10 mg/kg. Kaempferol was administered orally to the other three groups with dose of 5, 10, 15 mg/kg, respectively, followed by oral administration of NFP 10 mg/kg. Blood samples were collected through tail vein in heparinized plastic microcentrifuge tubes before and after drug administration. The plasma concentration of NFP was monitored with reversed phase high-performance liquid chromatography (RP-HPLC). Nimodipine was used as the internal standard. Statistical data evaluation was performed with Student's t-test and one-way analysis of variances.</p><p><b>RESULTS</b>The maximal plasma concentration (C(max)) of the three treated groups were 0.51, 0.70 and 0.81 microg/ml, respectively. The area under the concentration-time curve (AUC(0-8)) were 1.81, 2.83 and 3.63 microg/(h.ml(-1)), respectively. The C(max), AUC(0-8) and the mean retention time (MRT(0-8)) of NFP were significantly increased by simultaneous oral treatment with kaempferol (P<0.01). On the other hand, there were no significant differences in the mean peak value time in plasma (T(max)) and the elimination half-life (t1/2(ke)) between the control and the treated groups.</p><p><b>CONCLUSION</b>The concomitant oral use of kaempferol with NFP may influence the pharmacokinetic parameters of NFP in rats, which suggests that kaempferol might reduce the first-pass metabolism of NFP.</p>

Human pregnane X receptor-mediated transcriptional regulation of cytochrome P450 3A4 by some phytochemicals / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To test the effect on human pregnane X receptor (hPXR)-mediated transcription regulation of CYP3A4 by five selected phytochemicals.</p><p><b>METHODS</b>Transient cotransfection reporter gene assays in HepG(2) cells were performed with the hPXR expression plasmid and the reporter gene plasmid which contains XRE in the promoter of CYP3A4 linked to luciferase.</p><p><b>RESULTS</b>In the dose-effect study, soybean isoflavone, luteolin and curcumin induced the CYP3A4 transcription via PXR in an evident dose-dependent manner, but isorhamnetin and rutin did not. The inducibility of soybean isoflavone, luteolin and curcumin was also increased in concentrations between 1 micromol/L and 50 micromol/L, 24 h after induction, 50 micromol/L soybean isoflavone, luteolin and curcumin exhibited a 5.46-fold, 2.87-fold, and 2.07-fold increase respectively, compared with 0.1% DMSO treated cells. In the time-effect study, 10 micromol/L and 50 micromol/L soybean isoflavone, luteolin and curcumin induced CYP3A4 transcription between 12 h and 48 h, the strongest induction appeared in 48 h. 48 h after induction, 50 micromol/L soybean isoflavone, luteolin and curcumin exhibited a 6.72-fold, 3.24-fold, and 2.13-fold increase respectively, compared with 0.1% DMSO treated cells.</p><p><b>CONCLUSION</b>Three phytochemicals, i.e. soybean isoflavone, luteolin and curcumin stimulate the PXR-mediated transcription of CYP3A4. Isorhamnetin and rutin have no effect on the CYP3A4 transcription via PXR.</p>

Effects of phytoestrogens on gap junctional intercellular communication / 中华预防医学杂志

<p><b>OBJECTIVE</b>To observe effects of phytoestrogens quercetin (QC), Genistein (GEN), coumestrol (COM), and enterolactone (ENL) on gap junctional intercellular communication (GJIC) in HaCaT cells.</p><p><b>METHODS</b>HaCaT cells were exposed to QC, GEN, COM, and ENL at 0.1, 1.0, 10.0 and 100.0 micromol/L for 24 hours. The effects of phytoestrogens on GJIC were determined by fluorescence redistribution after photobleaching (FRAP) technique of using a laser scanning confocal microscope (LSCM).</p><p><b>RESULTS</b>QC did not affect the GJIC at 0.1-10.0 micromol/L, whereas, GEN, COM, and ENL exhibited inhibition on the GJIC in some extent at 0.1-10.0 micromol/L without showing significant cytotoxicity. The ratio of fluorescence recovery were between 31.77% to 37.06%, which were significantly decreased compared the vehicle control (44.74%).</p><p><b>CONCLUSION</b>The phytoestrogens GEN, COM, and ENL, but not QC, could inhibit the GJIC function in HaCaT cells at concentrations could be reached in human serum in some instance, indicating they could, under certain conditions, be cancer promoters. Therefore, it should be prudent to use these chemicals as pharmaceuticals or dietary supplements.</p>