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

Neurodegenerative diseases have emerged as major global health challenges, particularly in the context of an increasingly aging population. Traditionally, tobacco has been associated with various health risks, but recent research is uncovering a different aspect of this plant, suggesting that it may contain compounds with potential therapeutic benefits for neurodegenerative conditions. In this study, we have delved into the potential of specific bioactive compounds found in tobacco to serve as neuroprotective agents in the context of AD. Leveraging genetic engineering, we have developed a novel approach using neural progenitor cells (NPCs) derived from embryonic stem cells, equipped with an NF-κB reporter system. This system was instrumental in screening and identifying bioactive tobacco extracts. Our screenings revealed three compounds that exhibited significant inhibitory effects on NF-κB activation, a key mediator of neuroinflammation implicated in AD pathology. Among these compounds, rutin stood out for its profound neuroprotective effects in an NPC damage model induced by Amyloid-β25-35. These effects were manifested through a reduction in apoptotic cell death, an enhancement in cellular proliferation, and the activation of critical survival signaling pathways. This modulation is suggested to underlie rutin's anti-inflammatory and neuroprotective activities. These findings not only provide a scientific rationale for the application of tobacco-derived active molecules in AD therapy but also lay the foundation for exploration of their pharmaceutical value.