■中药中的有效成分对细胞色素P450酶(CYP450)活性的影响是中药处方中应考虑的关键因素。Physcion,大黄的主要活性成分。(Polysho科),具有广泛的药理活性。
■研究了physcion对CYP450活性的影响,为使用提供了理论依据。
■实验在汇集的人肝微粒体(HLM)中进行。用相应的底物和探针反应评价CYP450同种型的活性。空白HLM设置为阴性对照,和典型的抑制剂用作阳性对照。用LineweaverBurk图拟合抑制模型。还评估了physcion的浓度(0、2.5、5、10、25、50和100μMphyscion)和时间依赖性(0、5、10、15和30分钟)影响。
■Physcion以浓度依赖性方式抑制CYP2C9、2D6和3A4,IC50值为7.44、17.84和13.50μM,分别。CYP2C9和2D6的抑制与3.69和8.66μM的Ki值竞争,分别。CYP3A4的抑制是非竞争性的,Ki值为6.70μM。此外,只有CYP3A4的抑制是时间依赖性的,KI和Kinact参数分别为3.10μM-1和0.049min-1。
■在临床处方中应考虑physcon对CYP450的抑制作用,研究设计可用于评估CYP450与其他草药的相互作用。
UNASSIGNED: The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of Rheum spp. (Polygonaceae), possesses wide pharmacological activities.
UNASSIGNED: The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use.
UNASSIGNED: The experiments were conducted in pooled human liver microsomes (HLMs). The activity of CYP450 isoforms was evaluated with corresponding substrates and probe reactions. Blank HLMs were set as negative controls, and typical inhibitors were employed as positive controls. The inhibition model was fitted with Lineweaver Burk plots. The concentration (0, 2.5, 5, 10, 25, 50 and 100 μM physcion) and time-dependent (0, 5, 10, 15 and 30 min) effects of physcion were also assessed.
UNASSIGNED: Physcion suppressed CYP2C9, 2D6 and 3A4 in a concentration-dependent manner with IC50 values of 7.44, 17.84 and 13.50 μM, respectively. The inhibition of CYP2C9 and 2D6 was competitive with the Ki values of 3.69 and 8.66 μM, respectively. The inhibition of CYP3A4 was non-competitive with a Ki value of 6.70 μM. Additionally, only the inhibition of CYP3A4 was time-dependent with the KI and Kinact parameters of 3.10 μM-1 and 0.049 min-1, respectively.
UNASSIGNED: The inhibition of CYP450s by physcion should be considered in its clinical prescription, and the study design can be employed to evaluate the interaction of CYP450s with other herbs.