cinnamon, SIRT1, molecular docking, in silico


Background: Neurodegenerative diseases are the main cause of morbidity and disability in the elderly. SIRT1 activation has been gaining popularity as novel treatment target. Cinnamon is known to possess neuroprotective abilities, however the mechanism in which it protects the brain is still limited. Objective: This research aimed to determine the interaction between several cinnamon active compounds with SIRT1 Methods: We used in-silico method to determine the molecular interactions between cinnamon main compounds as the ligands to target protein SIRT1. SIRT1 3D structure was retrieved from the Protein Data Bank and 4 ligands (Cinnamaldehyde, Caffeic Acid, Epicatechin, and Trigonelline) structures were obtained from PubChem web server, and we used Resveratrol as positive control ligand. SwissADME, Pyrx, Pymol, and Biovia Discovery Studio software were utilized in this research Results: All four ligands fulfilled Lipinski Rule of 5 criteria therefore they are suitable for oral administration. It was discovered in this study that epicathecin had higher binding affinity than the control ligand Resveratrol and interacted with SIRT1 in the similar amino acid residue as Resveratrol did. The binding pocket interaction between all ligands and SIRT1 are the same. Conclusion: Epicathecin, as one of the main cinnamon compounds, may possess neuroprotective properties by interacting with SIRT1. We pproposed that further research be implemented to investigate epicathecin biological effects on SIRT1 in vitro or in vivo.


Erkkinen MG, Kim MO, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2018;10(4):a033118. . DOI:10.1101/cshperspect.a033118

Donmez G, Outeiro TF. SIRT1 and SIRT2: Emerging targets in neurodegeneration. EMBO Mol Med. 2013;5(3):344–52. . DOI:10.1002/emmm.201302451

Chi H, Chang HY, Sang TK. Neuronal cell death mechanisms in major neurodegenerative diseases. Int J Mol Sci. 2018;19(10):3082. . DOI:10.3390/ijms19103082

Machado de Oliveira R, F. Pais T, Fleming Outeiro T. Sirtuins: Common Targets in Aging and in Neurodegeneration. Curr Drug Targets. 2012;11(10):1270–80. . DOI:10.2174/1389450111007011270

Rivarti AW, Herawati L, Hidayati HB. Exercise Prevents Age-Related Memory Decline: the Role of Neurotrophic Factors. MNJ (Malang Neurol Journal). 2020;6(2):88–94. . DOI:10.21776/ub.mnj.2020.006.02.8

Manjula R, Anuja K, Alcain FJ. SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases. Front Pharmacol. 2021;11:1899. . DOI:10.3389/fphar.2020.585821

Ajami M, Pazoki-Toroudi H, Amani H, Nabavi SF, Braidy N, Vacca RA, et al. Therapeutic role of sirtuins in neurodegenerative disease and their modulation by polyphenols. Neurosci Biobehav Rev. 2017;73:39–47. . DOI:10.1016/j.neubiorev.2016.11.022

Zhong F, Liu L, Wei J-L, Hu Z-L, Li L, Wang S, et al. Brain-derived neurotrophic factor precursor in the hippocampus regulates both depressive and anxiety-like behaviors in rats. Front psychiatry. 2019;9:776.

Zhang Y, Anoopkumar-Dukie S, Arora D, Davey AK. Review of the anti-inflammatory effect of SIRT1 and SIRT2 modulators on neurodegenerative diseases. Eur J Pharmacol. 2020;867:172847. . DOI:10.1016/j.ejphar.2019.172847

Al-Dhubiab BE. Pharmaceutical applications and phytochemical profile of Cinnamomum burmannii. Pharmacogn Rev. 2012;6(12):125–31. . DOI:10.4103/0973-7847.99946

Khasnavis S, Pahan K. Cinnamon treatment upregulates neuroprotective proteins Parkin and DJ-1 and protects dopaminergic neurons in a mouse model of Parkinson’s disease. J Neuroimmune Pharmacol. 2014;9(4):569–81. . DOI:10.1007/s11481-014-9552-2

Yulug B, Kilic E, Altunay S, Ersavas C, Orhan C, Dalay A, et al. Cinnamon Polyphenol Extract Exerts Neuroprotective Activity in Traumatic Brain Injury in Male Mice. CNS Neurol Disord - Drug Targets. 2018;17(6):439–47. . DOI:10.2174/1871527317666180501110918

Angelopoulou E, Paudel YN, Piperi C, Mishra A. Neuroprotective potential of cinnamon and its metabolites in Parkinson’s disease: Mechanistic insights, limitations, and novel therapeutic opportunities. J Biochem Mol Toxicol. 2021;35(4):e22720. . DOI:10.1002/jbt.22720

de Ruyck J, Brysbaert G, Blossey R, Lensink MF. Molecular docking as a popular tool in drug design, an in silico travel. Adv Appl Bioinforma Chem. 2016;9(1):1. . DOI:10.2147/AABC.S105289

Muhammad DRA, Tuenter E, Patria GD, Foubert K, Pieters L, Dewettinck K. Phytochemical composition and antioxidant activity of Cinnamomum burmannii Blume extracts and their potential application in white chocolate. Food Chem. 2021;340:127983. . DOI:10.1016/j.foodchem.2020.127983

Dai H, Case AW, Riera T V., Considine T, Lee JE, Hamuro Y, et al. Crystallographic structure of a small molecule SIRT1 activator-enzyme complex. Nat Commun. 2015;6(1):1–10. . DOI:10.1038/ncomms8645

Sampangi-Ramaiah MH, Vishwakarma R, Shaanker RU. Molecular docking analysis of selected natural products from plants for inhibition of SARS-CoV-2 main protease. Curr Sci. 2020;118(7):1087–92. . DOI:10.18520/cs/v118/i7/1087-1092

Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):1–13. . DOI:10.1038/srep42717

Prasanth DSNBK, Murahari M, Chandramohan V, Panda SP, Atmakuri LR, Guntupalli C. In silico identification of potential inhibitors from Cinnamon against main protease and spike glycoprotein of SARS CoV-2. J Biomol Struct Dyn. 2021;39(13):4618–32. . DOI:10.1080/07391102.2020.1779129

Mullard A. Re-assessing the rule of 5, two decades on. Nat Rev Drug Discov. 2018;17(11):777. . DOI:10.1038/nrd.2018.197

Gupta M, Sharma R, Kumar A. Docking techniques in pharmacology: How much promising? Comput Biol Chem. 2018;76:210–7. . DOI:10.1016/j.compbiolchem.2018.06.005

Shargel, L., Andrew, B. C., & Wu-Pong S. Applied Biopharmaceutics & Pharmacokinetics, 7e [Internet]. McGraw Hill Medical; 2015 [cited 2022 Jan 2]. Available from:

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2012;64(SUPPL.):4–17. . DOI:10.1016/j.addr.2012.09.019

Athar Abbasi M, Raza H, Aziz-ur-Rehman, Zahra Siddiqui S, Adnan Ali Shah S, Hassan M, et al. Synthesis of novel N-(1,3-thiazol-2-yl)benzamide clubbed oxadiazole scaffolds: Urease inhibition, Lipinski rule and molecular docking analyses. Bioorg Chem. 2019;83:63–75. . DOI:10.1016/j.bioorg.2018.10.018

Do J, Kim N, Jeon SH, Gee MS, Ju YJ, Kim JH, et al. Trans-cinnamaldehyde alleviates amyloid-beta pathogenesis via the SIRT1-PGC1α-PPARγ pathway in 5XFAD transgenic mice. Int J Mol Sci. 2020;21(12):1–13. . DOI:10.3390/ijms21124492

Davari M, Hashemi R, Mirmiran P, Hedayati M, Sahranavard S, Bahreini S, et al. Effects of cinnamon supplementation on expression of systemic inflammation factors, NF-kB and Sirtuin-1 (SIRT1) in type 2 diabetes: A randomized, double blind, and controlled clinical trial. Nutr J. 2020;19(1):1–8. . DOI:10.1186/s12937-019-0518-3




How to Cite

Kalsum, U., Khotimah, H., Sulihah, N. T., Firdaus, T., Lisabilla, F. A., Fukata, E., Permatasari, H. K., & Andarini, S. (2022). NEUROPROTECTIVE EFFECT OF CINNAMON ACTIVE COMPOUNDS VIA ACTIVATION OF SIRT1: A MOLECULAR DOCKING APPROACH. Malang Neurology Journal, 8(2), 117–121.



Research Article