Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Phytother Res. 2012 Aug;26(8):1113-8. doi: 10.1002/ptr.3688. Epub 2011 Dec 9.
The aim of this study was to assess the influence of the Panax notoginseng saponins (PNS) on the activities of the drug-metabolizing enzymes cytochrome P450 (CYP450) 1A2, 2 C9, 2D6 and 3A4 in rats. The activities of CYP1A2, 2 C9, 2D6 and 3A4 were measured using specific probe drugs. After pretreatment for 1 week with PNS or physiological saline (control group), probe drugs caffeine (10 mg/kg; CYP1A2 activity), tolbutamide (15 mg/kg; CYP2C9 activity), metoprolol (20 mg/kg; CYP2D6 activity) and dapsone (10 mg/kg; CYP3A4 activity) were administered to rats by intraperitoneal injection. The blood was then collected at different times for ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis. The data showed that PNS exhibited an induction effect on CYP1A2 by decreasing caffeine C(max) (36.3%, p < 0.01) and AUC(0-∞) (22.77%, p < 0.05) and increasing CL/F (27.03%, p < 0.05) compared with those of the control group. Western blot analysis was used to detect the effect of PNS on the protein level of CYP1A2, and the results showed that PNS could upregulate the protein expression of CYP1A2. However, no significant changes in CYP2C9, 2D6 or 3A4 activities were observed. In conclusion, the results indicate that PNS could induce CYP1A2, which may affect the disposition of medicines primarily dependent on the CYP1A2 pathway. Our work may be the basis of related herb-drug interactions in the clinic.
本研究旨在评估三七总皂苷（PNS）对大鼠细胞色素 P450（CYP450）1A2、2C9、2D6 和 3A4 代谢酶活性的影响。采用特异性探针药物测定 CYP1A2、2C9、2D6 和 3A4 的活性。用 PNS 或生理盐水（对照组）预处理 1 周后，通过腹腔注射给予大鼠探针药物咖啡因（10mg/kg；CYP1A2 活性）、甲苯磺丁脲（15mg/kg；CYP2C9 活性）、美托洛尔（20mg/kg；CYP2D6 活性）和氨苯砜（10mg/kg；CYP3A4 活性）。然后在不同时间采集血液进行超高效液相色谱/串联质谱（UPLC-MS/MS）分析。数据显示，与对照组相比，PNS 通过降低咖啡因 Cmax（36.3%，p<0.01）和 AUC（0-∞）（22.77%，p<0.05）以及增加 CL/F（27.03%，p<0.05），对 CYP1A2 表现出诱导作用。Western blot 分析用于检测 PNS 对 CYP1A2 蛋白水平的影响，结果表明 PNS 可上调 CYP1A2 蛋白表达。然而，CYP2C9、2D6 或 3A4 活性没有明显变化。总之，结果表明 PNS 可诱导 CYP1A2，这可能会影响主要依赖 CYP1A2 途径代谢的药物的处置。我们的工作可能是临床相关草药-药物相互作用的基础。
