Study on Virtual Screening of Active Components from Yiqi Ziyin Decoction in the Treatment of Type 2 Diabetes Mellitus / 中国药房

ABSTRACT

OBJECTIVE： To conduct virtual screening for active component， target and pathway of TCM Yiqi ziyin decoction in the treatment of type 2 diabetes mellitus， and to elucidate the pharmacodynamic mechanism of this decoction in the treatment of type 2 diabetes mellitus at molecular level so as to provide theoretical basis for its popularization， application and rational organization. METHODS： Chemical compounds isolated from 10 ingredients of Yiqi ziyin decoction were retrieved from Handbook of Chemical Constituents of Original TCM Plants. Drug/drug-like molecules for the treatment of type 2 diabetes mellitus were retrieved from DrugBank database. Three-dimensional molecular structures of each component were downloaded from PubChem Compound database. The structure was optimized by using Cerius2 4.10 software， and the small molecular data set of Yiqi ziyin decoction was established. Using “type 2 diabetes mellitus” as keywords， target protein of type 2 diabetes mellitus were retrieved and screened from target protein databases， and their three-dimensional structures were downloaded from protein database. The selected compound molecules （ligands） were docked with target proteins （receptors）， and small molecules with high activity （sorted according to the values of Degree and Betweenness） and target proteins with high correlation were found. The interaction mechanism between ligand and receptor was discussed by taking the fine docking of selected small molecules with target protein （N-trans-caffeoyl tyrosine molecule and glycogen synthase kinase-3β） as an example. RESULTS： There were 732 kinds of chemical components and 127 drug/drug-like molecules； 30 target proteins of type 2 diabetes mellitus were screened. According to the values of Degree and Betweenness， 8 molecules with high activity （such as N-trans-caffeoyl tyrosine， hyperin and so on） and 10 target proteins with high correlation （such as carbonic anhydrase1， glycogen synthetase kinase-3β and so on） were screened out. The interaction between N-trans-caffeoyl tyrosine and glycogen synthase kinase-3β could form hydrogen bonds and π alkylation， thus affecting the structural stability and activity of the latter and reducing blood glucose. CONCLUSIONS： In this study， it found there existed not only one molecule compound interacting with multiple targets， but also different molecule compound  interacting with the same target on Yiqi Ziyin decoction for the treatment of type 2 diabetes mellitus by virtual screening， it revealed the characteristics of multi-component and multi-target synergism of TCM prescriptions at the molecular level， providing reference for screening lead compounds and structural modification of new drug for diabetes mellitus.