In Silico Screening and DFT Analysis of Nelumbo nucifera Phytochemicals as Potential BACE-1 Inhibitors for Alzheimer’s disease

Rohit Todkar; Pramodkumar Shirote; Shrinivas Mohite

doi:10.56782/pps.379

Published : 2025-10-20

Vol. 23 No. 4 (2025)

In Silico Screening and DFT Analysis of Nelumbo nucifera Phytochemicals as Potential BACE-1 Inhibitors for Alzheimer’s disease

Rohit Todkar

Pramodkumar Shirote

Shrinivas Mohite

DOI: https://doi.org/10.56782/pps.379

Abstract

Alzheimer's disease (AD) stands as one of the primary neurological disorders affecting humans. This condition is marked by deterioration of central nervous system function. The enzyme β-secretase (BACE-1) plays a crucial part in AD pathogenesis by initiating the destruction of the amyloid precursor protein (APP). Consequently, BACE-1 has become a significant focus for therapeutic interventions in AD. Nelumbo nucifera phytochemical structures have been virtually scrutinized for the expansion of potent and selective therapeutic compounds. In silico analysis of 24 different phytochemical structures from Nelumbo nucifera have been carried out against the BACE-1 to explore the anti-Alzheimer potential. Anonaine, asimilobine, dehydroanonaine, liriodenine, and roemerin were found to be prominently binding with BACE-1 and found to be more stable in DFT analysis, which indicated physicochemical exploration of the Nelumbo nucifera may result in potent and selective anti-Alzheimer agents.

Keywords:

Alzheimer, Nelumbo nucifera, β-secretase, In Silico, Docking and DFT analysis

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Todkar, R., Shirote, P., & Mohite, S. (2025). In Silico Screening and DFT Analysis of Nelumbo nucifera Phytochemicals as Potential BACE-1 Inhibitors for Alzheimer’s disease. Prospects in Pharmaceutical Sciences, 23(4), 29–36. https://doi.org/10.56782/pps.379

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References

1. Cummings, J.; Zhou, Y.; Lee, G.; Zhong, K.; Fonseca, J.; Cheng, F. Alzheimer’s disease drug development pipeline: 2024. Alzheimers Dement. (NY). 2024, 10(2), Art. No: e12465. DOI: 10.1002/trc2.12465

2. Potbhare, M.S.; Barik, R.; Khobragade, D.S. Management of Alzheimer’s Disease : A Review of Herbal Drugs Having Potential Pharmacological and Therapeutic Activity. J. Young Pharm. 2023, 15(1), 13-30. DOI: 10.5530/097515050344

3. Temviriyanukul, P.; Sritalahareuthai, V.; Promyos, N.; Thangsiri, S.; Pruesapan, K.; Srinuanchai, W.; Nuchuchua, O.; Siriwan, D.; On-nom, N.; Suttisansanee, U. The Effect of Sacred Lotus (Nelumbo nucifera) and Its Mixtures on Phenolic Profiles, Antioxidant Activities, and Inhibitions of the Key Enzymes Relevant to Alzheimer’s Disease. Molecules 2020, 25(16), Art. No: 3713. DOI: 10.3390/molecules25163713

4. Khan, S.; Khan, H.U.; Khan, F.A.; Shah, A.;Wadood, A.; Ahmad, S.; Almehmadi, M.; Alsaiari, A.A.; Shah, F.U.; Kamran, N. Anti-Alzheimer and Antioxidant Effects of Nelumbo nucifera L. Alkaloids, Nuciferine and Norcoclaurine in Alloxan-Induced Diabetic Albino Rats. Pharmaceuticals 2022, 15(10), Art. No: 1205. DOI: 10.3390/ph15101205

5. Mitra, K.; Raihan, M.A.; Rahman, M.A.; Rouf, R.; Reza, H.M.; Shaikh, J.U.; Muhammad, I. Therapeutic Potential of Nelumbo nucifera (Sacred Lotus) in CNS Disorders. Dhaka Univ. J. Pharm. Sci. 2021, 20(3), 347 358. DOI: 10.3329/dujps.v20i3.59800

6. Divakaran, D.; Sriariyanun, M.; Suyambulingam, I.; Mavinkere Rangappa, S.; Siengchin, S. Exfoliation and physico-chemical characterization of novel bioplasticizers from Nelumbo nucifera leaf for biofilm application. Heliyon 2023, 9(12), Art. No: e22550. DOI: 10.1016/j.heliyon.2023.e22550

7. Xu, H.; Wang, C.; Gong, L. Hypoglycemic activity in vivo and in vitro of the Lotus (Nelumbo nucifera Gaertn.) seed skin (testa) phenolic-rich extracts. Food Chem. X. 2024, 22, Art. No: 101282. DOI: 10.1016/j.fochx.2024.101282

8. Kumaran, A.; Ho, C.C.; Hwang, L.S. Protective effect of Nelumbo nucifera extracts on beta amyloid protein induced apoptosis in PC12 cells, in vitro model of Alzheimer’s disease. J. Food Drug Anal. 2018, 26(1), 172-181. DOI: 10.1016/j.jfda.2017.01.007

9. Ahn, J.H.; Kim, E.S.; Lee, C. Chemical constituents from Nelumbo nucifera leaves and their anti-obesity effects. Bioorganic Med. Chem. Lett. 2013, 23(12), 3604-3608. DOI: 10.1016/j.bmcl.2013.04.013

10. Cho, E.J.; Yokozawa, T.; Rhyu, D.Y.; Kim, H.Y.; Shibahara, N.; Park, J.C. The inhibitory effects of 12 medicinal plants and their component compounds on lipid peroxidation. Am. J. Chin. Med. 2003, 31(6), 907-917. DOI: 10.1142/S0192415X03001648

11. Hu, P.; Ge, X.; Gao, M.; Wang, X.; Zhang, Y.; Li, Y. Nelumbo nucifera Gaertn: An updated review of the antitumor activity and mechanisms of alkaloids. Pharmacol. Res. Mod. Chin. Med. 2022, 5, Art. No: 100167. DOI: 10.1016/j.prmcm.2022.100167

12. Huang, C.F.; Chen, Y.W.; Yang, C.Y.; Lin, H.Y.; Way, T.D.; Chiang, W. Extract of lotus leaf (Nelumbo nucifera) and its active constituent catechin with insulin secretagogue activity. J. Agric. Food Chem. 2011, 59(4), 1087-1094. DOI: 10.1021/jf103382h

13. Jiang, X.L.; Wang, L.; Wang, E.J.; Zhang, G.L.; Chen, B.; Wang, M.K. Flavonoid glycosides and alkaloids from the embryos of Nelumbo nucifera seeds and their antioxidant activity. Fitoterapia 2018, 125, 184-190. DOI: 10.1016/j.fitote.2018.01.009

14. Kashiwada, Y.; Aoshima, A.; Ikeshiro, Y.; Chen, Y.P.; Furukawa, H.; Itoigawa, M. Anti HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids. Bioorg. Med. Chem. 2005, 13, 443 448. DOI: 10.1016/j.bmc.2004.10.020

15. Kaur, P.; Kaur, L.; Kaur, N.; Singh, A. A brief review on pharmaceutical uses of Nelumbo nucifera. J. Pharmacogn. Phytochem. 2019, 8(3), 3966-3972.

16. Ki, H.K.; Sang, W.C.; Shi, Y.R.; San, U.C.; Kang, R.L. Phytochemical constituents of Nelumbo nucifera. Nat. Prod. Sci. 2009, 15(2), 90-95.

17. Lin, H.Y.; Kuo, Y.H.; Lin, Y.L.; Chiang, W. Antioxidative effect and active components from leaves of lotus (Nelumbo nucifera). J. Agric. Food Chem. 2009, 57, 6623-6629. DOI: 10.1021/jf900950z

18. Liu, S.; Li, D.; Huang, B.; Chen, Y.; Lu, X.; Wang, Y. Inhibition of pancreatic lipase, α-glucosidase, α-amylase, and hypolipidemic effects of the total flavonoids from Nelumbo nucifera leaves. J. Ethnopharmacol. 2013, 149, 263-269. DOI: 10.1016/j.jep.2013.06.034

19. Mukherjee, P.K.; Mukherjee, D.; Maji, A.K.; Rai, S.; Heinrich, M. The sacred lotus (Nelumbo nucifera) - phytochemical and therapeutic profile. J. Pharm. Pharmacol. 2009, 61, 407 422. DOI: 10.1211/jpp/61.04.0001

20. Ono, Y.; Hattori, E.; Fukaya, Y.; Imai, S.; Ohizumi, Y. Anti-obesity effect of Nelumbo nucifera leaves extract in mice and rats. J. Ethnopharmacol. 2006, 106, 238 244. DOI: 10.1016/j.jep.2005.12.036

21. Paudel, K.R.; Panth, N. Phytochemical profile and biological activity of Nelumbo nucifera. Evid.-based Complement. Altern Med. 2015, 2015, Art. No: 789124. DOI: 10.1155/2015/789124

22. Temviriyanukul, P.;Sritalahareuthai, V.; Promyos, N.; Thangsiri, S.;Pruesapan, K.;Srinuanchai, W. The Effect of Sacred Lotus (Nelumbo nucifera) and Its Mixtures on Phenolic Profiles, Antioxidant Activities, and Inhibitions of the Key Enzymes Relevant to Alzheimer’s Disease. Molecules 2020, 25(16), Art. No: 3713. DOI: 10.3390/molecules25163713

23. Wang, H.M.; Yang, W.L.; Yang, S.C.; Chen, C.Y. Chemical constituents from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. Chem. Nat. Compd. 2011, 47, 316-318. DOI: 10.1007/s10600-011-9919-z

24. Wen, Y.P.; Fu, H.J.; Chen, Q.; Lan, C.; Qin, D.L.; Wu, J.M. Exploring the therapeutic potential of Nelumbo nucifera leaf extract against amyloid-beta-induced toxicity in the Caenorhabditis elegans model of Alzheimer’s disease. Front. Pharmacol. 2024, 15, Art. No: 1408031. DOI: 10.3389/fphar.2024.1408031

25. Wu, C.H.; Yang, M.Y.; Chan, K.C.; Chung, P.J.;Ou, T.T.; Wang, C.J. Improvement in high-fat diet-induced obesity and body fat accumulation by a Nelumbo nucifera leaf flavonoid-rich extract in mice. J. Agric. Food Chem. 2010, 58, 7075-7081. DOI: 10.1021/jf101415v

26. Zhang, Y.; Xu, Y.; Wang, Q.; Zhang, J.; Dai, X.; Miao, S. The antioxidant capacity and nutrient composition characteristics of lotus (Nelumbo nucifera Gaertn.) seed juice and their relationship with color at different storage temperatures. Food Chem. X. 2023, 18, Art. No: 100669. DOI:10.1016/j.fochx.2023.100669

27. DassaultSystèmes, BIOVIA Discovery Studio Visualizer, (2020).

28. Crystal structure of BACE1 in complex with 2-aminooxazoline 3 azaxanthene inhibitor 2. Available online: https://www.rcsb.org/structure/5i3w (accessed on 30 August 2023).

29. Dallakyan, S.; Olson, A.J. Small-Molecule Library Screening by Docking with PyRx. Methods Mol. Biol. 2015, 1263, 243-50. DOI:10.1007/978-1-4939-2269-7_19

30. Jordan, J.B.; Whittington, D.A.; Bartberger, M.D.; Sickmier, E.A.; Chen, K.; Cheng, Y. Fragment-Linking Approach Using 19F NMR Spectroscopy to Obtain Highly Potent and Selective Inhibitors of β-Secretase. J. Med. Chem. 2016, 59, 3732 3749. DOI: 10.1021/acs.jmedchem.5b01917

31. Daina, A., Michielin, O., Zoete, V. Swiss ADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017, 7, Art. No: 42717. DOI: 10.1038/srep42717

32. Walsh, E.J. ACD/ChemSketch 1.0 (freeware); ACD/ChemSketch 2.0 and its Tautomers, Dictionary, and 3D Plug ins; ACD/HNMR 2.0; ACD/CNMR 2.0, J. Chem. Educ. 1997, 74. DOI: 10.1021/ed074p905

33. Rochlani, S.; Bhatia, M.; Rathod, S.; Choudhari, P; Dhavale, R. Exploration of limonoids for their broad spectrum antiviral potential via DFT, molecular docking and molecular dynamics simulation approach. Nat. Prod. Res. 2023, 38(5), 891 896. DOI: 10.1080/14786419.2023.2202398

34. Bakale, R.D.; Phatak, P.S.; Rathod, S.S.; Choudhari, P.B.; Rekha, E.M. In vitro and in silico exploration of newly synthesized triazolyl isonicotinohydrazides as potent antitubercular agents. J. Biomol. Struct. Dyn. 2023, 1372 1391. DOI: 10.1080/07391102.2023.2291826

35. Rathod, S.; Bhande, D.; Pawar, S.; Gumphalwad, K.; Choudhari, P.; More, H. Identification of Potential Hits against Fungal Lysine Deacetylase Rpd3 via Molecular Docking, Molecular Dynamics Simulation, DFT, In-Silico ADMET and Drug Likeness Assessment. Chem. Afr. 2023, 7, 1151–1164. DOI: 10.1007/s42250-023-00766-5

36. Bursch, M.; Mewes, J.M.; Hansen, A.; Grimme, S. Best-Practice DFT Protocols for Basic Molecular Computational Chemistry. Angew. Chem., Int. Ed. 2022, 61(42), Art. No: e202205735. DOI: 10.1002/anie.202205735

37. Jensen F. Atomic orbital basis sets. WIREs Comput. Mol. Sci. 2013, 33, 273–295. DOI: 10.1002/wcms.1123

38. Mardirossian, N.; Head-Gordon, M. Thirty years of density functional theory in computational chemistry: an overview and extensive assessment of 200 density functionals. Mol. Phys. 2017, 115, 2315 2372. DOI: 10.1080/00268976.2017.1333644

39. Piela, L. Chasing the Correlation Dragon: Density Functional Theory (DFT). In Ideas of Quantum Chemistry, 3rd ed.; Piela, L., Ed.; Elsevier: Amsterdam, Netherlands, 2020; 1, pp. 191–252. DOI: 10.1016/B978-0-44-464248-6.00011-9

40. Tirado-Rives, J.; Jorgensen, W.L. Performance of B3LYP density functional methods for a large set of organic molecules. J. Chem. Theory Comput. 2008, 4(2), 297 306. DOI: 10.1021/ct700248k

41. Neese, F. Software update: The ORCA program system—Version 5.0. WIREs Comput. Mol. Sci. 2022, 12(5), Art. No: e1606. DOI: 10.1002/WCMS.1606

42. Neese, F.; Wennmohs, F.; Becker, U.; Riplinger, C. The ORCA quantum chemistry program package. J. Chem. Phys. 2020, 152, Art. No: 224108. DOI: 10.1063/5.0004608.

43. Snyder, H.D.; Kucukkal, T.G. Computational Chemistry Activities with Avogadro and ORCA. J. Chem. Educ. 2021, 98, 1335 1341. DOI: 10.1021/acs.jchemed.0c00959

44. Rathod, S.; Shinde, S.; Choudhari, P.; Sarkate, A.; Chaudhari, S.; Shingan, A. Exploring binding potential of two new indole alkaloids from Nauclea officinalis against third and fourth generation EGFR: druglikeness, in silico ADMET, docking, DFT, molecular dynamics simulation, and MMGBSA study. Nat. Prod. Res. 2025, 39(10), 2970-2977. DOI: 10.1080/14786419.2023.2301678

45. Kilbile, J.T.; Tamboli, Y.; Ansari, S.A.; Rathod, S.S.; Choudhari, P.B.; Alkahtani, H.; Sapkal, S.B. Synthesis, Biological Evaluation, and Computational Studies of 6 Fluoro 3 (Piperidin 4 yl) 1,2 Benzisoxazole Sulfonamide Conjugates. Polycycl. Aromat. Compd. 2023, 44(6), 4157 177. DOI: 10.1080/10406638.2023.2247117

46. Puthanveedu, V.; Muraleedharan, K.Phytochemicals as potential inhibitors for COVID-19 revealed by molecular docking, molecular dynamic simulation and DFT studies. Struct. Chem.2022, 33, 1423 1443. DOI: 10.1007/s11224 022 01982-4

Rohit Todkar

sandiphonmane@gmail.com

Affiliation:

Rajarambapu College of Pharmacy, Kasegaon, Shivaji University, Kolhapur-415409, Maharashtra, India. India

Bio Statement (e.g., department and rank)

Department of Chemistry

Pramodkumar Shirote

padmpamod@ediffmail.com

Affiliation:

Sarojani College of Pharmacy, Kolhapur, Shivaji University, Kolhapur-416013, Maharashtra, India. India

Bio Statement (e.g., department and rank)

Department of Chemistry

Shrinivas Mohite

mohite_shrinivas@rediffmail.com

Affiliation:

Rajarambapu College of Pharmacy, Kasegaon, Shivaji University, Kolhapur-415409, Maharashtra, India. India

Bio Statement (e.g., department and rank)

Department of Chemistry