Integrated Network Pharmacology and Molecular Docking Identify Neuroprotective Candidates from Nicotiana tabacum L. Against Alzheimer’s Disease
Abstract
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.
Downloads
References
Birks, J. S., & Harvey, R. J. (2018). Donepezil for dementia due to Alzheimer’s disease. Cochrane Database of Systematic Reviews, 2018(6). https://doi.org/10.1002/14651858.CD001190.pub3
Hanslik, K. L., & Ulland, T. K. (2020). The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer’s Disease. Frontiers in Neurology, 11. https://doi.org/10.3389/fneur.2020.570711
Heitman, E., & Ingram, D. K. (2017). Cognitive and neuroprotective effects of chlorogenic acid. Nutritional Neuroscience, 20(1), 32–39. https://doi.org/10.1179/1476830514Y.0000000146
Lauretti, E., Dincer, O., & Praticò, D. (2020). Glycogen synthase kinase-3 signaling in Alzheimer’s disease. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1867(5), 118664. https://doi.org/10.1016/j.bbamcr.2020.118664
Li, S., Ding, Q., & Wang, X. (2021). “Network Target” Theory and Network Pharmacology. In Network Pharmacology (pp. 1–34). Springer Singapore. https://doi.org/10.1007/978-981-16-0753-0_1
Li, Z., & Gong, C. (2025). NLRP3 inflammasome in Alzheimer’s disease: molecular mechanisms and emerging therapies. Frontiers in Immunology, 16. https://doi.org/10.3389/fimmu.2025.1583886
Marucci, G., Buccioni, M., Ben, D. D., Lambertucci, C., Volpini, R., & Amenta, F. (2021). Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology, 190, 108352. https://doi.org/10.1016/j.neuropharm.2020.108352
McManus, R. M., & Latz, E. (2024). NLRP3 inflammasome signalling in Alzheimer’s disease. Neuropharmacology, 252, 109941. https://doi.org/10.1016/j.neuropharm.2024.109941
Pinzi, L., & Rastelli, G. (2019). Molecular Docking: Shifting Paradigms in Drug Discovery. International Journal of Molecular Sciences, 20(18), 4331. https://doi.org/10.3390/ijms20184331
Sayas, C. L., & Ávila, J. (2021). GSK-3 and Tau: A Key Duet in Alzheimer’s Disease. Cells, 10(4), 721. https://doi.org/10.3390/cells10040721
Wu, X., Singh, S. K., Patra, B., Wang, J., Pattanaik, S., & Yuan, L. (2025). An overview of the regulation of specialized metabolism in tobacco. Current Plant Biology, 41, 100431. https://doi.org/10.1016/j.cpb.2024.100431
Zhang, W., Pan, X., Fu, J., Cheng, W., Lin, H., Zhang, W., & Huang, Z. (2024). Phytochemicals derived from Nicotiana tabacum L. plant contribute to pharmaceutical development. Frontiers in Pharmacology, 15. https://doi.org/10.3389/fphar.2024.1372456
Articles published in Indonesian Journal of Life Sciences are licensed under a Creative Commons Attribution-ShareAlike 4.0 International license. You are free to copy, transform, or redistribute articles for any lawful purpose in any medium, provided you give appropriate credit to the original author(s) and Indonesian Journal Life of Sciences, link to the license, indicate if changes were made, and redistribute any derivative work under the same license. Copyright on articles is retained by the respective author(s), without restrictions. A non-exclusive license is granted to Indonesian Journal Life of Sciences to publish the article and identify itself as its original publisher, along with the commercial right to include the article in a hardcopy issue for sale to libraries and individuals. By publishing in Indonesian Journal Life of Sciences, authors grant any third party the right to use their article to the extent provided by the Creative Commons Attribution-ShareAlike 4.0 International license.
