Integrated Network Pharmacology and Molecular Docking Identify Neuroprotective Candidates from Nicotiana tabacum L. Against Alzheimer’s Disease

The neuroprotective potential of compounds from Nicotiana tabacum L. against Alzheimer’s disease was evaluated using network pharmacology, molecular docking, and ADME profiling. 25 compounds were screened, and the intersection of predicted targets with Alzheimer’s disease associated proteins yielded 90 overlapping proteins. Network topology using Degree prioritized three hub targets, IL-1β (Degree: 37), GSK3β (Degree: 25), and AChE (Degree: 19). Docking in YASARA against IL-1β (5R8Q), GSK3β (5K5N), and AChE (4EY7) produced binding energy ranges of -6.673 to -8.680, -9.769 to -10.614, and -10.349 to -12.275 kcal/mol, respectively. The β-amyrin ranked best among test ligands for IL-1β at -6.885 kcal/mol and for GSK3β at -10.178 kcal/mol, while citrostadienol ranked best for AChE at -10.881 kcal/mol. Dual-target profiles supported 28-Isofucosterol for GSK3β and AchE, and gramisterol for IL-1β and AChE. BOILED Egg analysis supported BBB-oriented prioritization of candidates with TPSA <79 Ų, while highly lipophilic sterol-type leads indicate formulation-dependent developability. Overall, Nicotiana tabacum L. provides non-nicotine sterol and triterpenoid scaffolds as multi-target chemotypes spanning inflammation, kinase signaling, and cholinergic dysfunction in Alzheimer’s disease.