三七总皂苷主要成分对人肝微粒体CYP3A4酶的抑制作用研究

目的：研究三七总皂苷主要成分人参皂苷Rg1、人参皂苷Rb1和三七皂苷R1对人肝微粒体CYP3A4酶的体外抑制作用.方法：采用人肝微粒体体外孵育法,在孵育体系中分别加入不同浓度的人参皂苷Rg1、人参皂苷Rb1和三七皂苷R1与探针底物睾酮共孵育,用LC-MS /MS 法测定代谢产物6β-羟基睾酮的生成量反映CYP3A4酶活性的影响.结果：人参皂苷Rg1在2～1 000 μmol·L-1的测试浓度范围内对CYP3A4未见剂量相关的抑制作用;人参皂苷Rb1在2～200 μmol·L-1的测试浓度范围内对CYP3A4未见剂量相关的抑制作用,在1 000 μmol·L-1的测试浓度下对CYP3A4具有轻微抑制作用;三七皂苷R1在2～1 000 μmol·L-1的测试浓度范围内对CYP3A4的IC50为126 μmol·L-1（＞100 μmol·L-1）.结论：三七总皂苷3个主要有效成分单体对CYP3A4酶的体外抑制作用不同,人参皂苷Rg1无抑制作用,人参皂苷Rb1高浓度下有轻微抑制作用,三七皂苷R1有弱抑制作用,三七总皂苷制剂与CYP3A4酶代谢相关的药物之间产生相互作用的可能性低.

Inhibition of Panax Notoginsenosides on Human Liver Microsomes CYP3A4

Objective ： To investigate the inhibitory effect of such main components of Panax notoginsenosides as ginsenoside Rg1, ginsenoside Rbl and notoginsenoside R1 on human liver microsomes CYP3A4 in vitro. Methods： The human liver microsomes were re- spectively incubated with ginsenoside Rgl, ginsenoside Rb1 and notoginsenoside R1 at different concentrations at the present of testoster- one. LC-MS/MS was used to detect the metabolite 613-hydroxytestosterone in the incubation systems to reflect the specific substrate of CYP3A4. Ketoconazole was used as the positive control. Results： Ginsenoside Rgl （2-1 000μmol · L-1 ） and ginsenoside Rb1 （2-200 μmol · L-1 ） had no inhibitory effect on CYP3A4. Ginsenoside Rb1（ 1 000 μmol · L-1 ） had mild inhibitory action on CYP3A4, and notoginsenoside R1（2-1 000μmol · L-1 ） showed the inhibition with IC50 of 126 μmol · L-1 （ 〉 100 μmol · L-1 ）. Conclusion： The 3 kinds of Panax notoginsenosides have different inhibitory action on human liver microsomes CYP3A4 in vitro. Panax notoginsenosides ex- hibit limited inhibition on CYP3A4, so show little interaction with the drugs metabolized by CYP3A4.