应用大鼠肝微粒体筛选对细胞色素P4502D6有抑制作用的中药

目的从17种中药(单体、提取物和注射液)中快速筛选出对细胞色素P4502D6(CYP2D6)亚型有抑制作用的中药,建立高通量筛选对CYP2D6有抑制作用中药的技术平台。方法取大鼠空白肝微粒体,分别加入17种中药,HPLC法测定大鼠肝微粒体中CYP2D6的探针药物右美沙芬(DM)的代谢率,通过代谢率降低的现象初步筛选出能抑制肝微粒体中CYP2D6代谢的药物。结果槲皮素、黄芩苷、厚朴提取物、清开灵注射液、盐酸川芎嗪注射液可明显降低DM的代谢率(P<0.01)。结论初步筛选出槲皮素、黄芩苷、厚朴提取物、清开灵注射液、盐酸川芎嗪注射液这5种中药可抑制肝微粒体CYP2D6酶活性。此方法可作为高通量筛选对CYP2D6活性有抑制作用中药的技术平台。

Screening of Chinese materia medica possessed inhibitory effect on cytochrome P4502D6 in liver microsomes of rats

Objective To screen the chemical components, extract, and injection, which have the inhibitory effect on cytochrome P4502D6 (CYP2D6) in liver microsomes of rats, from 17 kinds of Chinese materia medica (CMM) and develop a technical method for screening CMM possessed inhibitory effect on CYP2D6 in liver microsomes of rats by high throughout. MethodsThe liver microsomes of rats were incubated with 17 kinds of CMM at the presence of Dextromethorphan (DM). DM Metabolic rate (DX/DM, DX: Dextrophan, metabolites of DM) in liver microsomal reconstituted system was measured by HPLC and used as probe to determine the activity of CYP2D6. The inhibition of CMM on rat CYP2D6 was identified by decreasing the metabolic rate. ResultsQuercetin, baicalin, extract of Flos Magnoliae Officinalis, Qingkailing Injection, and Tetramethylpytazine Hydrochloride Injection inhibited the DM metabolic rate (P<0.01). ConclusionFive kinds of CMM have been obtained, they are quercetin, baicalin, extract of Flos Magnoliae Officinalis, Qingkailing Injection, and Tetramethylpytazine Hydrochloride Injection, which can inhibit the activity of CYP2D6 in liver microsomes of rats. The method mentioned above can be used as a useful technique to high throughout screening of CMM possessed the inhibitory effect on CYP2D6.