Author(s):
Mokhamad Fahmi Rizki Syaban, Rislan Faiz Muhammad, Basyar Adnani, Gumilar Fardhani Ami Putra, Nabila Erina Erwan, Safira Dita Arviana, Agung Dwi Krisnayana, Dedy Budi Kurniawan
Email(s):
mokhamadfahmi@gmail.com
DOI:
10.52711/0974-360X.2022.00513 
Address:
Mokhamad Fahmi Rizki Syaban1*, Rislan Faiz Muhammad2, Basyar Adnani2, Gumilar Fardhani Ami Putra2, Nabila Erina Erwan2, Safira Dita Arviana2, Agung Dwi Krisnayana1, Dedy Budi Kurniawan2
1Faculty of Medicine, Brawijaya Univesity, Malang, 65111 Indonesia.
2Master Program in Biomedical Science, Faculty of Medicine, Brawijaya Univesity, Malang, 65111, Indonesia.
*Corresponding Author
Published In:
Volume - 15,
Issue - 7,
Year - 2022
ABSTRACT:
Alzheimer's disease (AD) is the most common form of dementia. In several studies we reviewed, curcumin can inhibit formation, extension, and destabilization of Amyloid A4 protein. Aim: This study aims to prove the consistency of curcumin as a candidate therapy for Alzheimer's disease using in silico approach. Methods: Biomolecular experimental study was conducted using in silico method supported by protein database, Pymol, Discovery studio, and PyRx software. A comprehensive literature search was conducted to found the potential target for Alzheimer's disease. We found Beta-secretase 1, Amyloid A4 protein, Gamma-secretase, and Glycogen synthase kinase (GSK)-3ß as a protein target. Pharmacokinetic analysis was conducted based on the Lipinski Rule of Five criteria on the Lipinski Rule of Five websites and using the PreADMET website. Results: From the pharmacokinetic analysis, curcumin had met all the Lipinski and PreADMET criteria. The HIA and plasma binding test results showed 94.4% and 88%, which represent a good pharmacokinetic and bioavailability profile as a drug. GSK-3ß had the strongest binding affinity with curcumin as recorded as -8.3 kcal/mol compared with the other four protein targets in this analysis. Conclusion: The strongest binding affinity between curcumin and GSK-3ß reveals the potential target protein for Alzheimer's Disease therapy. Those interactions represent the potential involvement in the pathogenesis of Alzheimer's Disease with a modification of the additional sites on the tau molecule. This drug candidate discovery shows a preferable pharmacokinetics and bioavailability substance profile with a promising target through the Structure-based Drug Design (SBDD) approach. However, curcumin ability for BBB penetration still needs to be modified to improve its pharmacokinetic properties for becoming a novel Alzheimer's disease drug
Cite this article:
Mokhamad Fahmi Rizki Syaban, Rislan Faiz Muhammad, Basyar Adnani, Gumilar Fardhani Ami Putra, Nabila Erina Erwan, Safira Dita Arviana, Agung Dwi Krisnayana, Dedy Budi Kurniawan. Molecular Docking Studies of Interaction Curcumin against Beta-secretase 1, Amyloid A4 Protein, Gamma-secretase and Glycogen Synthase Kinase-3β as Target Therapy for Alzheimer Disease. Research Journal of Pharmacy and Technology. 2022; 15(7):3069-4. doi: 10.52711/0974-360X.2022.00513
Cite(Electronic):
Mokhamad Fahmi Rizki Syaban, Rislan Faiz Muhammad, Basyar Adnani, Gumilar Fardhani Ami Putra, Nabila Erina Erwan, Safira Dita Arviana, Agung Dwi Krisnayana, Dedy Budi Kurniawan. Molecular Docking Studies of Interaction Curcumin against Beta-secretase 1, Amyloid A4 Protein, Gamma-secretase and Glycogen Synthase Kinase-3β as Target Therapy for Alzheimer Disease. Research Journal of Pharmacy and Technology. 2022; 15(7):3069-4. doi: 10.52711/0974-360X.2022.00513 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2022-15-7-35
REFERENCES:
1. Selkoe DJ. Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol. 2004 Nov;6(11):1054–61. doi.org/10.1038/ncb1104-1054.
2. Tiwari S. Atluri V. Kaushik A. Yndart A. Nair M. Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019 Jul 19;14:5541–54. doi.org/10.2147/IJN.S200490.
3. Korolev I. Alzheimer’s Disease: A Clinical and Basic Science Review. Med Stud Res J. 2014 Jan 1;4:24–33.
4. Querfurth HW. LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010 Jan 28;362(4):329–44. doi.org/10.1056/NEJMra0909142.
5. Alzheimer’s Association. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement. 2015;11(3):332–84. doi.org/10.1016/j.jalz.2015.02.003.
6. Tran L. Ha-Duong T. Exploring the Alzheimer amyloid-β peptide conformational ensemble: A review of molecular dynamics approaches. Peptides. 2015 Jul;69:86–91. doi.org/10.1016/j.peptides.2015.04.009.
7. Armstrong, R. A. The Pathogenesis of Alzheimer’s Disease: A Reevaluation of the “Amyloid Cascade Hypothesis.” Int. J. Alzheimers Dis. 2011, 2011. https://doi.org/10.4061/2011/630865.
8. Hampel H. Vassar R. De Strooper B. Hardy J. Willem M. Singh N. et al. The β-Secretase BACE1 in Alzheimer’s Disease. Biol Psychiatry. 2020 Feb;S0006322320300639. doi.org/10.1016/j.biopsych.2020.02.001.
9. Wolfe MS. γ-Secretase as a target for Alzheimer’s disease. Adv Pharmacol San Diego Calif. 2012;64:127–53. doi.org/10.1016/B978-0-12-394816-8.00004-0.
10. Avila J. Wandosell F. Hernández F. Role of glycogen synthase kinase-3 in Alzheimer’s disease pathogenesis and glycogen synthase kinase-3 inhibitors. Expert Rev Neurother. 2010 May;10(5):703–10. doi.org/10.1586/ern.10.40.
11. Venugopalan P. Deepthi TV. Chemical and Pharmacological Studies on Curcuminoids. 2014;11.
12. Nagarnaik M. Sarjoshi A. Bodkhe A. Khanal B. Pise M. Pandya G. Characterization of active constituents in Turmeric powder and validation of method for curcumin in samples. Asian J Res Chem. 2015;8(10):643. doi.org/10.5958/0974-4150.2015.00102.9.
13. Prasad S. Aggarwal BB. Turmeric. the Golden Spice: From Traditional Medicine to Modern Medicine. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects [Internet]. 2nd ed. Boca Raton (FL): CRC Press/Taylor & Francis; 2011 [cited 2021 Feb 12]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK92752/
14. Chen M, Du Z-Y. Zheng X. Li D-L. Zhou R-P. Zhang K. Use of curcumin in diagnosis, prevention, and treatment of Alzheimer’s disease. Neural Regen Res. 2018 Apr;13(4):742–52. doi.org/10.4103/1673-5374.230303. doi.org/10.4103/1673-5374.230303.
15. Voulgaropoulou SD. van Amelsvoort TAMJ. Prickaerts J. Vingerhoets C. The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies. Brain Res. 2019 Dec 15;1725:146476. doi.org/10.1016/j.brainres.2019.146476. doi.org/10.1016/j.brainres.2019.146476.
16. Jadhav RP. Kengar MD. Narule OV. Koli VW. Kumbhar SB. A Review on Alzheimer’s Disease (AD) and its Herbal Treatment of Alzheimer’s Disease. Asian J Res Pharm Sci. 2019;9(2):112. doi.org/10.5958/2231-5659.2019.00017.1.
17. G S. B S. S P. A Review on Curcumin Nanoparticles and Its Controlled Delivery to Treat Degenerative Diseases-Indian Journals [Internet]. [cited 2021 Aug 4]. Available from: https://www.indianjournals.com/ijor.aspx?target=ijor:ajpt&volume=3&issue=4&article=017
18. den Haan J. Morrema THJ. Rozemuller AJ. Bouwman FH. Hoozemans JJM. Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics. Acta Neuropathol Commun. 2018 Aug 9;6(1):75. doi.org/10.1186/s40478-018-0577-2.
19. Lee W-H. Loo C-Y. Bebawy M. Luk F. Mason RS. Rohanizadeh R. Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Curr Neuropharmacol. 2013 Jul;11(4):338–78. doi.org/10.2174/1570159X11311040002.
20. Patil SV. Patil VK. Patil PA. Review on herbal medicines of alzheimer’s disease. Asian J Res Pharm Sci. 2020;10(3):171. doi.org/10.5958/2231-5659.2020.00033.8.
21. Yueniwati Y. Syaban MFR. Erwan NE. Putra GFA. Krisnayana AD. Molecular Docking Analysis of Ficus religiosa Active Compound with Anti-Inflammatory Activity by Targeting Tumour Necrosis Factor Alpha and Vascular Endothelial Growth Factor Receptor in Diabetic Wound Healing. Open Access Maced J Med Sci. 2021;9:1031–6. doi.org/10.3889/oamjms.2021.7068
22. Rahman PA. Syaban MFR. Anoraga SG. Sabila FL. Molecular Docking Analysis from Bryophyllum pinnatum Compound as A COVID-19 Cytokine Storm Therapy. Open Access Maced J Med Sci. 2022;10:779–84. doi.org/10.3889/oamjms.2022.8412
23. Yueniwati Y, Syaban MF, Faratisha IF, Yunita KC, Putra GF, Kurniawan DB, et al. Molecular docking approach of natural compound from herbal medicine in java against severe acute respiratory syndrome coronavirus-2 receptor. Open Access Maced J Med Sci. 2021;9:1181-6. doi.org/10.3889/oamjms.2021.6963
24. Bhat R. Xue Y. Berg S. Hellberg S. Ormö M. Nilsson Y. et al. Structural Insights and Biological Effects of Glycogen Synthase Kinase 3-specific Inhibitor AR-A014418. J Biol Chem. 2003 Nov;278(46):45937–45. doi.org/10.1074/jbc.M306268200.
25. Bustanji Y. Taha MO. Almasri IM. Al-Ghussein MAS. Mohammad MK. Alkhatib HS. Inhibition of Glycogen Synthase Kinase by Curcumin: Investigation by Simulated Molecular Docking and Subsequent in vitro/in vivo Evaluation. J Enzyme Inhib Med Chem. 2009 Jun;24(3):771–8.
26. Lauretti E. Dincer O. Praticò D. Glycogen Synthase Kinase-3 Signaling in Alzheimer’s Disease. Biochim Biophys Acta BBA - Mol Cell Res. 2020 May;1867(5):118664. doi.org/10.1016/j.bbamcr.2020.118664.
27. Sayas CL. Ávila J. GSK-3 and Tau: A Key Duet in Alzheimer’s Disease. Cells. 2021 Mar 24;10(4):721. doi.org/10.3390/cells10040721.
28. Hemalatha K. Girija K. Evaluation of Drug Candidature of some Benzimidazole Derivatives as Biotin Carboxylase Inhibitors: Molecular docking and Insilico studies. Asian J Res Pharm Sci. 2016;6(1):15. doi.org/10.5958/2231-5659.2016.00002.3.
29. Teleanu D. Chircov C. Grumezescu A. Volceanov A. Teleanu R. Blood-Brain Delivery Methods Using Nanotechnology. Pharmaceutics. 2018 Dec 11;10(4):269.
30. Syaban MFR. Erwan NE. Syamsuddin MRR. Zahra AF. Sabila FL. Insilico Study and Analysis Antibacterial Activity of Beta-glucan against Beta-Lactamase and Protein Binding Penicillin-2A. Research Journal of Pharmacy and Technology. 2022; 15(5):1948-2. doi.org/10.52711/0974-360X.2022.00324
31. Pinzi L. Rastelli G. Molecular Docking: Shifting Paradigms in Drug Discovery. Int J Mol Sci. 2019 Sep 4;20(18):4331. doi.org/10.3390/ijms20184331.
32. Syaban MFR. Faratisha IFD. Yunita KC, Erwan E. Kurniawan DB. Putra GFA. Molecular Docking and Interaction Analysis of Propolis Compounds Against SARS-CoV-2 Receptor. Journal of Tropical Life Science. 2022;12(2):12. doi.org/10.11594/jtls.12.02.08
33. Chandran M. George S. Santhalingam K. Gangwar P. Molecular Docking of 3, 5, 7-Trihydroxy-2-(4-Hydroxy-3-Methoxyphenyl)- 4h-Chromen-4-One Derivatives Against Il-6 for Rheumatoid Arthritis. 2011;4.
34. Dhananjayan K. Sumathy A. Palanisamy S. Molecular Docking Studies and in-vitro Acetylcholinesterase Inhibition by Terpenoids and Flavonoids. 2013;7.
35. Sharma R. Kumari N. Ashawat MS. Verma CPS. Standardization and phytochemical screening analysis for herbal extracts: Zingiber officinalis, Rosc., Curcuma longa Linn., Cinnamonum zeylanicum Nees., Piper longum, Linn., Boerhaavia diffussa Linn. Asian J Pharm Technol. 2020;10(3):127. doi.org/10.5958/2231-5713.2020.00022.7.
36. Sindhu TJ. Arathi KN. Devi A. Aswathi TA. Noushida M. Midhun M. et al. Synthesis, Molecular Docking and Antibacterial Studies of Novel Azole derivatives as Enoyl ACP Reductase Inhibitor in Escherichia coli. Asian J Res Pharm Sci. 2019;9(3):174. doi.org/10.5958/2231-5659.2019.00027.4.
37. Griebel G. Stemmelin J. Lopez-Grancha M. Boulay D. Boquet G. Slowinski F. et al. The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer’s disease in rodents. Sci Rep. 2019 Dec;9(1):18045. doi.org/10.1038/s41598-019-54557-5.
38. Fiorentini A. Rosi MC. Grossi C. Luccarini I. Casamenti F. Lithium Improves Hippocampal Neurogenesis, Neuropathology and Cognitive Functions in APP Mutant Mice. Zars T, editor. PLoS ONE. 2010 Dec 20;5(12):e14382. doi.org/10.1371/journal.pone.0014382.
39. Ly PTT. Wu Y. Zou H. Wang R. Zhou W. Kinoshita A. et al. Inhibition of GSK3β-Mediated BACE1 Expression Reduces Alzheimer-Associated Phenotypes. J Clin Invest. 2013 Jan 2;123(1):224–35. doi.org/10.1172/JCI64516.
40. Lee SJ. Chung YH. Joo KM. Lim HC. Jeon GS. Kim D. et al. Age-Related Changes in Glycogen Synthase Kinase 3β (GSK3β) Immunoreactivity in the Central Nervous System of Rats. Neurosci Lett. 2006 Dec;409(2):134–9. doi.org/10.1016/j.neulet.2006.09.026.