Discovery of combinational targets for Alzheimer’s disease based on traditional Chinese medicinal prescription (654.10)

Abstract

The present one‐drug, one‐target paradigm for anti‐Alzheimer’s disease (AD) treatment appears to be clinically unsuccessful, the combinational targets which composed of several biomolecules based on bio‐network may be optimum for the discovery of anti‐AD drugs. This study aims to search the combinational targets for AD based on traditional Chinese medicine (TCM) using network pharmacology strategy. The nootropic effects of five TCM prescriptions, namely Liuwei‐Dihuang decoction (LW), Bawei‐Dihuang decoction (BW), Huanglian‐Jiedu decoction (HL), Danggui‐Shaoyao‐San (DSS) and Tiaoxin Recipe (TXF), were validated by cognitive behavior test in senescence accelerated mouse prone 8 (SAMP8), and the combinational therapeutic targets were investigated using cDNA microarray, RT‐PCR, bioinformatics and computational biology techniques. The results showed LW, BW, HL, DSS, and TXF significantly improve the cognitive behavior of SAMP8. There are 117 genes expression in hippocampus and 122 genes expression in cerebral cortex regulated by LW, BW, HL, DSS and TXF in SAMP8. These genes regulated by five prescriptions involve in the biomolecular network. The hub nodes included 9 molecules, that is STUB1, STRN4, RPS6KA1, ROCK1, MAP3K3, TICAM2, MAPT, UBE2D2 and PHB. Furthermore, RPS6KA1, SLC17A7 and FHIT are the common nodes effected by one of five prescriptions and may be potential therapeutic target candidates for AD.Grant Funding Source: the National Science and Technology Major Project (2012ZX09301003‐002‐001, 2013ZX09508104)