Neuroprotective Effects of Bioactive Molecules Derived from Tobacco as Potential Therapeutic Candidates for Alzheimer Disease

Abstract Neurodegenerative diseases are significant global health challenges, particularly with an aging population. While tobacco is traditionally linked to health risks, recent studies suggest it may contain compounds beneficial for neurodegenerative conditions. Herein, we explore the potential of bioactive compounds in tobacco as neuroprotective agents for Alzheimer’s disease (AD). Using genetic engineering, we developed a novel approach with neural progenitor cells (NPCs) derived from embryonic stem cells, equipped with an NF-κB reporter system to screen tobacco extracts. Our screenings identified three compounds with significant inhibitory effects on NF-κB activation, a key mediator of neuroinflammation in AD. Among these, rutin exhibited profound neuroprotective effects in an NPC damage model induced by Amyloid-β25-35, reducing apoptotic cell death, enhancing cellular proliferation, and activating critical survival signaling pathways. This modulation underlies rutin’s anti-inflammatory and neuroprotective activities. Together, our findings support the potential of tobacco-derived compounds in AD therapy and lay the foundation for further exploration of their pharmaceutical value.