Network pharmacology and bioinformatics approach reveals the therapeutic activity and action mechanism of curcumin in Alzheimer disease

Abstract

Abstract Curcumin is a natural anti-inflammatory and antioxidant substance which plays a major role in reducing the amyloid plaques formation, which is the major cause of Alzheimer’s disease (AD). Consequently, a methodical approach was used to select the potential protein targets of curcumin in AD through network pharmacology. In this study, through integrative methods AD targets of curcumin through SwissTargetPrediction database, STITCH database, BindingDB, PharmMapper, Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM) database were predicted followed by gene enrichment, network construction, network topology, and docking studies. Gene ontology analysis facilitated identification of a list of possible AD targets of curcumin (74 targets genes). The correlation of the obtained targets with AD was analysed by Gene Ontology (GO) pathway enrichment analyses and Kyoto Encyclopaedia of Genes and Genomes (KEGG). Applying network pharmacological approach to identified key genes. Further, we performed molecular docking for analysing the mechanism of curcumin. To validate the temporospatial expression of key genes in human central nervous system (CNS), we searched the Human Brain Transcriptome (HBT) dataset. We identify top five key genes namely, PPARγ, MAPK1, STAT3, KDR and APP. Further validate the expression profiling of these key genes in publicly available brain data expression profile databases. This study concluded with novel insights into the therapeutic mechanisms of curcumin which in the future will ease the treatment of AD with the clinical application of curcumin.