In Silico Evaluation of Dichrostachys cinerea Phytochemicals Against Alzheimer’s Disease: Network Pharmacology and Molecular Dynamics Insights
TL;DR
This study provides the first systems-level computational evidence for D. cinerea’s multi-target therapeutic potential in AD, establishing a molecular foundation for future experimental validation.
Abstract
Background: Alzheimer’s disease (AD) affects over 55 million individuals worldwide, and current therapies offer only symptomatic relief without modifying disease progression. The complex, multi-factorial pathology of AD — involving neuroinflammation, oxidative stress, tau hyperphosphorylation, and amyloid-β accumulation — demands a multi-target therapeutic strategy. Dichrostachys cinerea, a plant with well-documented ethnomedicinal use, presents unexplored neuroprotective potential. Aim: To investigate the multi-target anti-Alzheimer’s potential of phytochemicals derived from D. cinerea using an integrated computational approach combining GC-MS profiling, network pharmacology, molecular docking, and molecular dynamics simulation. Methods: GC-MS analysis of the hydroethanolic extract identified 134 metabolites, which were subjected to drug-likeness and ADMET screening. Network pharmacology was performed using SwissTargetPrediction and GeneCards to identify 249 common AD-related targets. PPI network analysis via STRING and CytoHubba identified hub genes. Molecular docking was carried out using AutoDock Vina against IL6 (PDB: 1ALU), GSK3β (PDB: 1Q5K), and PPARG (PDB: 6MS7). Molecular dynamics (MD) simulations were performed for 100 ns using GROMACS. Results: Among 134 identified metabolites, 92.5% exhibited favourable drug-like properties. Network analysis revealed IL6, PPARG, and GSK3β as key hub targets among 249 overlapping AD-related genes. Andrographolide demonstrated the highest binding affinities across all three targets (IL6: −8.4 kcal/mol; GSK3β: −8.8 kcal/mol; PPARG: −8.4 kcal/mol). MD simulations confirmed superior stability of the andrographolide–GSK3β complex with consistent RMSD convergence and persistent hydrogen bonding throughout 100 ns. Conclusion: This study provides the first systems-level computational evidence for D. cinerea’s multi-target therapeutic potential in AD, establishing a molecular foundation for future experimental validation. Major Findings: Andrographolide from D. cinerea showed strong, stable binding to IL6, GSK3β, and PPARG—key AD hub targets. The andrographolide–GSK3β complex had the best docking score (−8.8 kcal/mol) and greatest MD stability over 100 ns.