ELUCIDATING THE MULTI-TARGETED EFFECTS OF Z-GUGGULSTERONE IN ALZHEIMER’S DISEASE: INSIGHTS FROM NETWORK PHARMACOLOGY AND MOLECULAR DOCKING

Abstract

Z-Guggulsterone (Z-GS) has exhibited notable neuroprotective and memory-enhancing effects.  The current bioinformatic analysis aims to elucidate the potential therapeutic effects of Z-GS against Alzheimer’s disease (AD) using network pharmacology and molecular docking.  Initially, the pharmacokinetic profile of Z-GS was assessed following the identification of potential target proteins from online databases. To elucidate the functional implications of the shared targets, GO enrichment and KEGG analysis were utilized to identify the relevant signaling pathways. Furthermore, a PPI network was subjected to functional and topological analyses, leading to the identification of hub targets. Finally, molecular docking was done to validate the interactions between Z-GS and the identified hub targets, providing insights into the binding affinity and interaction modes. The analysis identified ten key genes BACE1, BCHE, CTSD, PARP2, DRD2, SRD5A1, GRM1, CYP19A1, MAPK3, and TGFBR1. These are pivotal genes that significantly contribute to the complex pathology and progression of AD. Hence, this integrated analysis prioritized these genes as key targets, suggesting that Z-GS exerts potential therapeutic effects by modulating these critical proteins implicated in AD pathogenesis.