摘要
目的：传统名方六味地黄方（LWDH）对治疗2型糖尿病具有较好疗效,α-葡萄糖苷酶（α-GC）是2型糖尿病发生发展的关键靶点,该文采用虚拟筛选技术分析LWDH中抑制α-GC活性的有效成分。方法：从文献中获取LWDH中己知的21种主要化学成分及代谢产物结构组成配体分子库,采用分子对接法将配体与α-GC的C端,N端分别逐一对接后,进行复合物自由结合能的数据分析;并以α-GC抑制剂阿卡波糖（ACR）的结合能作为阈值,预测LWDH中抑制α-GC活性潜在的有效成分。结果：与ACR和α-GC之N端,C端的结合能（-38.38,-36.38 J·mol-1）相比较,分别有2种LWDH的主要成分与α-GC的N端或C端结合能较低,其作用力主要为氢键和范德华力,且这几种成分均属于组成药物泽泻中的四环三萜类化合物。结论：基于分子对接的虚拟筛选可推断LWDH中抑制α-葡萄糖苷酶活性的有效物质,为深入开展六味地黄方治疗2型糖尿病的机理研究提供了科学数据。
Traditional famous prescription Liuwei Dihuang prescription（ LWDH） has a good effect in treating type 2 diabetes. α-Glucosidase（ α-GC） is the key target of development of type 2 diabetes. In this paper,we analyzed active α-GC inhibitors from LWDH by using virtual screening technique. Method： We obtained structures of 21 known main chemical components and metabolites in LWDH from literatures to compose the molecular ligand library. Ligands were combined with α-GC at terminal N and terminal C by using molecular docking. After docking,the lowest binding energy（ LBE） of the complexes was calculated to predict potential active α-GC inhibitors,with LBEs of α-GC inhibitor acarbose（ ACR） as the threshold（-38. 38,-36. 38 J·mol-1 at terminals N and C,respectively）. Result： Two components in LWDH,which belong to tetracyclic triterpenoids of Alismatis Rhizoma,had lower LBEs with α-GC than ACR at terminals N and C,respectively,with hydrogen bonds and Van der Waals force as the main acting forces. Conclusion： Virtual screening based on molecular docking could help us to predict active α-GC inhibitors in LWDH,and provide scientific evidence for further studies on the mechanism of LWDH in the treatment of type 2 diabetes.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2018年第5期64-70,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
江苏高校优势学科建设工程项目(PAPD)
江苏高校品牌专业建设工程项目(PPZY2015A070)
关键词
六味地黄方
虚拟筛选
Α-葡萄糖苷酶抑制剂
分子对接
2型糖尿病
Liuwei Dihuang prescription
virtual screening
α-glucosidase inhibitor
molecular docking
type 2 diabetes
