Exploring the regulatory mechanism of Nao Tai Fang on vascular Dementia's biological network based on cheminformatics and transcriptomics strategy

Ethnopharmacological relevance: Nao Tai Fang (NTF) is modified from Buyang Huanwu Decoction. Modern pharmacological research showed that NTF has a good anti-cerebral ischemic effect and can improve the learning and memory ability of cerebrovascular disease.

Aim: The purpose of this study is to explore the regulation mechanism of NTF on the regulation mechanism of vascular dementia (VD)'s biological network based on chemoinformatics and transcriptomics strategies.

Method: First, the bilateral common carotid artery ligation method was used to create a rat VD model. After NTF intervention for 30 days, the treatment effect was evaluated by HE staining and water maze experiment. Then, the Agilent mRNA expression profiling chip was used to obtain mRNA expression data of hippocampal tissues of VD model rats before and after NTF intervention, and microarray analysis was used to screen for genes with significant differential expression. The BATMAN database was utilized to obtain the potential targets of NTF and the Genecards and OMIM were utilized to collect the VD potential genes. The cytoscape was utilized to construct and analyze the networks.

Result: The animal experiments showed that NTF can improve VD. A total of 180 up-regulated proteins and 289 down-regulated proteins were identified. The top 20 up- and down-regulated differentially expressed genes were utilized to construct differentially expressed gene's protein-protein interaction (PPI) network. A total of 677 NTF potential targets and 550 VD genes were obtained and were utilized to construct NTF-VD PPI network. The cheminformatics analysis showed that NTF can regulate a lot of biological processes and signaling pathways (such as inflammation modules, vasodilation and contraction modules, hypoxia modules, angiogenesis, coagulation, neurovascular unit modules, Neuroactive ligand-receptor interaction, Calcium signaling pathway, Serotonergic synapse).

Conclusion: NTF may play a role in the treatment of VD through the targets, signaling pathways and biological processes discovered in this study.