Integrative Network Pharmacology and Docking Analysis of Moringa oleifera in Alzheimer's Disease: Dual Targeting of MAPK1 and STAT3 by Active Phytochemical Compounds

Abstract

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder with limited therapeutic options. This study evaluated the potential of Moringa oleifera as a multi-target therapeutic candidate for AD using an integrative network pharmacology and molecular docking approach. From 209 screened phytochemicals, six compounds—hesperetin, cianidanol, campesterol, 24-methylenecholesterol, β-sitosterol, and 28-isoavenasterol acetate—met drug-likeness and oral bioavailability criteria. Target prediction identified 233 overlapping genes between M. oleifera compounds and AD-associated genes, forming a densely interconnected protein–protein interaction network with key hub proteins including HSP90AA1, SRC, MAPK1, and STAT3. Functional enrichment analysis revealed significant involvement in MAPK signaling, neuroactive ligand–receptor interaction, arachidonic acid metabolism, and amyloid-beta response pathways. Molecular docking demonstrated that sterol derivatives, particularly campesterol and 24-methylenecholesterol, exhibited the strongest binding affinities to MAPK1 (−8.2 kcal/mol), stabilizing critical residues such as ALA52, ILE31, VAL39, ASP111, and ASP167. In contrast, flavonoids such as hesperetin and cianidanol showed moderate binding affinities but more favorable pharmacokinetic and safety profiles. Several compounds also interacted with STAT3 at moderate affinities, suggesting partial modulation of neuroinflammatory signaling. Overall, these findings suggest that M. oleifera may exert neuroprotective effects through dual targeting of MAPK1-driven neuronal dysfunction and STAT3-mediated inflammation. These results are based on computational analyses and should be considered hypothesis-generating, warranting further experimental validation.

Received: 18 December 2025 | Revised: 2 February 2026 | Accepted: 24 February 2026

Conflicts of Interest

The authors declare that they have no conflicts of interest to this work. The authors declare that there are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data Availability Statement

The present study did not generate any new experimental data. All data used in this work were retrieved from publicly available databases, including phytochemical databases (such as PubChem), disease-associated gene databases, and protein structure repositories (Protein Data Bank). These resources are publicly accessible, and all relevant database sources are appropriately cited within the manuscript.

Author Contribution Statement

Israr Hussain: Methodology, Writing – original draft. Itazaz Ul Haq: Methodology. Muhammad Rahiyab: Software. Li Pinyi: Validation, Data curation. Ishaq Khan: Resources. Syed Shujait Ali: Writing – review & editing, Visualization. Mohammad Ali: Investigation. Arshad Iqbal: Conceptualization, Formal analysis, Supervision, Project administration.