AI-Driven Scientific Prompting and Sequential Discovery Pipeline for Nrf2-Targeted Predictive Modeling and Therapeutic Insights in Alzheimer's Disease Using Glucomoringin from Moringa oleifera

Abstract

Alzheimer’s disease (AD) remains a major global health challenge with limited diseasemodifying therapies. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a central regulator of antioxidant and anti- inflammatory responses, has emerged as a promising therapeutic target. Natural products, particularly glucosinolates, provide diverse scaffolds for Nrf2 modulation. This review synthesizes current evidence on the neuroprotective potential of glucomoringin, a major glucosinolate from Moringa oleifera, as an Nrf2 activator in AD, and proposes an AI-driven sequential discovery pipeline to accelerate therapeutic development. A systematic literature search (2010–2025) across PubMed, Scopus, Web of Science, and Google Scholar identified studies on Nrf2 signaling in AD, glucomoringin neuroprotection, and AI applications in drug discovery. Evidence indicates diminished Nrf2 activity in AD brains, contributing to oxidative stress and neuroinflammation. Glucomoringin and its metabolite moringin significantly activate Nrf2 in neuronal and microglial models, enhancing antioxidant enzymes (HO-1, NQO1, SOD) and suppressing NF-κB-mediated inflammation. In silico studies confirm favorable Keap1 binding and drug-like properties. AI-driven approaches, including large language model (LLM)-based hypothesis generation, molecular docking, machine learning prediction, and ADMET modeling, are transforming natural product discovery by enabling rapid screening, property prediction, and iterative optimization. Integrating scientific prompting with predictive modeling and experimental validation offers a powerful strategy to overcome traditional bottlenecks. Glucomoringin thus represents a promising phytochemical for Nrf2- targeted AD intervention, and AI-enabled sequential pipelines may accelerate its translation into effective neuroprotective therapies.