摘要
目的 探讨五酯胶囊通过CYP3A4影响其他药物代谢的作用机制。方法 首先采用分子对接技术虚拟筛选五酯胶囊中6种主要活性成分(即五味子甲素、五味子乙素、五味子丙素、五味子醇甲、五味子醇乙及五味子酯甲)和阳性对照药物伊曲康唑与CYP3A4的作用机制,应用Molecular Operating Enviroment软件的Dock功能进行分子对接,得出对接评分(S)。之后利用表面等离子共振(SPR)评估各活性成分及阳性对照与CYP3A4的亲和力。结果 分子对接结果显示五酯胶囊的6种主要成分与CYP3A4在空间结构上互补性高,其中五味子酯甲的S值最低,为-8.4517。SPR显示五味子酯甲与CYP3A4的亲和力最强,K_(d)值为3.21×10^(-8) mol·L^(-1),其次为五味子甲素,五味子醇甲与五味子丙素与CYP3A4的亲和力相对较弱。亲和力拟合曲线显示五酯胶囊的6种主要活性成分与CYP3A4亲和力均较好。结论 五味子酯甲与CYP3A4的结合力最强,相较于伊曲康唑,其他成分与CYP3A4同样存在较强的结合能力,这可能是五酯胶囊通过CYP3A4影响其他药物代谢的主要原因。
Objective To determine the mechanism of Wuzhi capsules affecting the metabolism of other drugs through CYP3A4.Methods Molecular docking was used to screen the mechanism of six main active components of Wuzhi capsules:schisandrin A,schisandrin B,schisandrin C,schisandrol A,schisandrol B,and schisantherin A,along with the positive control drug itraconazole with CYP3A4.The docking function of Molecular Operating Environment software was used to obtain the docking scores (S).Subsequently,surface plasmon resonance (SPR) was used to assess the affinity of each active component and the positive control with CYP3A4.Results The molecular docking showed that the six main components of Wuzhi capsules were highly complementary to CYP3A4 in terms of space structure,among which schisantherin A had the lowest S-value of -8.4517.SPR showed that schisantherin A had the strongest binding affinity to CYP3A4,with a K_(d) of 3.21×10^(-8) mol·L^(-1),followed by schisandrin A.The affinity of schisandrin C,and schisandrol A propin to CYP3A4 was relatively weak.In the affinity fitting curves,the six main components of pentosan capsules had better affinity with CYP3A4.Conclusion Schisantherin A shows the strongest binding to CYP3A4.As compared with the itraconazole,other components also show strong binding ability to CYP3A4,which may be the main reason how Wuzhi capsules affect the metabolism of other drugs through CYP3A4.
作者
叶倩倩
蒋跃平
葛成昱
王柠柠
刘韶
YE Qian-qian;JIANG Yue-ping;GE Cheng-yu;WANG Ning-ning;LIU Shao(Department of Pharmacy,Xiangya Hospital of Central South University,Changsha 410008;National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Changsha 410008)
出处
《中南药学》
CAS
2024年第12期3187-3192,共6页
Central South Pharmacy
基金
湖南省自然科学基金(No.2022JJ80047)
国家老年疾病临床医学研究中心资助项目(No.2021LNJJ20)。
关键词
五酯胶囊
分子对接
表面等离子共振
相互作用
Wuzhi capsule
molecular docking
surface plasmon resonance
drug interaction
