Analisis Interaksi Alfa Tokoferol dan Asam Oleat terhadap Asetilkolin dan Asetilkolinesterase Otak dengan Analisis Doking Molekuler

Nurul Nazla; Emni Purwoningsih; Luhu Avianto Tapiheru; Melviana Lubis

doi:10.55606/jurrike.v5i2.10309

Authors

Nurul Nazla Universitas Muhammadiyah Sumatera Utara
Emni Purwoningsih Universitas Muhammadiyah Sumatera Utara
Luhu Avianto Tapiheru Universitas Muhammadiyah Sumatera Utara
Melviana Lubis Universitas Muhammadiyah Sumatera Utara

DOI:

https://doi.org/10.55606/jurrike.v5i2.10309

Keywords:

Acetylcholine, Alpha Tocopherol, Alzheimer's, Molecular Docking, Oleic Acid

Abstract

Acetylcholine is an essential neurotransmitter in modulating the function of the human central nervous system. The pathogenesis of Alzheimer’s disease is characterized by an acetylcholine deficit resulting from the accumulation of beta-amyloid plaques and tau protein neurofibrillary tangles, which directly trigger cognitive decline in patients. To determine the binding energy and inhibition constants for the interactions between acetylcholine and acetylcholinesterase proteins with alpha-tocopherol and oleic acid. In silico analysis using molecular docking methods with Autodock Tools and Marvin Sketch software. The results of the docking analysis were then visualized using Discovery Studio and LigandScout software. The binding energies and inhibition constants of acetylcholine with oleic acid and alpha-tocopherol were -4.96 kcal/mol and 229.99 μM, and -6.35 kcal/mol and 22.13 μM, respectively. The binding energies and inhibition constants of acetylcholinesterase for oleic acid and alpha-tocopherol were -5.11 kcal/mol and 179.45 μM, and -8.35 kcal/mol and 0.75845 μM, respectively. Oleic acid and alpha-tocopherol can interact with acetylcholine and acetylcholinesterase through the formation of hydrogen bonds.

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References

Anthony, J. (2015). What Is an Inhibitory Constant (Ki) and How Does It Relate to Understanding Drug Interactions?

Bekdash, R. A. (2021). The Cholinergic System, the Adrenergic System and the Neuropathology of Alzheimer’s Disease. International Journal of Molecular Sciences, 22(3), 1273. https://doi.org/10.3390/ijms22031273

Breijyeh, Z., & Karaman, R. (2020). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25(24), 5789. https://doi.org/10.3390/molecules25245789

Castellano, J. M., Garcia-Rodriguez, S., Espinosa, J. M., Millan-Linares, M. C., Rada, M., & Perona, J. S. (2019). Oleanolic Acid Exerts a Neuroprotective Effect Against Microglial Cell Activation by Modulating Cytokine Release and Antioxidant Defense Systems. Biomolecules, 9(11), 683. https://doi.org/10.3390/biom9110683

Chen, Z. R., Huang, J. B., Yang, S. L., & Hong, F. F. (2022). Role of Cholinergic Signaling in Alzheimer’s Disease. Molecules, 27(6), 1816. https://doi.org/10.3390/molecules27061816

Dina, S. P., Herowati, R., & Nurrochmad, A. (2019). Uji In-Vitro Penghambatan Enzim Asetilkolinesterase dan Identifikasi Fitokimia Fraksi Aktif Ekstrak Etanol Buah Mengkudu (Morinda citrifolia L.).

Emeralda, G., Riyanti, S., & Karlina, Y. (2023). Potensi Ekstrak Jahe Merah (Zingiber officinale Roscoe var. Sunti), Pegagan (Centella asiatica (L.) Urb.) dan Kayu Manis (Cinnamomum burmanni) sebagai Herbal Penunda Kepikunan. Kartika: Jurnal Ilmiah Farmasi, 8(2), 67–76. https://doi.org/10.26874/KJIF.V8I2.650

Fadzillah, S. N., Hernawati, D., & Putra, R. R. (2024). Analisis In Silico: Aktivitas Antiinflamasi dan Prediksi Toksisitas Senyawa Metabolit Sekunder Daun Ciplukan (Physalis peruviana L.). Bioscientist: Jurnal Ilmiah Biologi, 12(1), 517. https://doi.org/10.33394/bioscientist.v12i1.9592

Fujii, T., Mashimo, M., & Moriwaki, Y. (2017). Physiological Functions of the Cholinergic System in Immune Cells. Journal of Pharmacological Sciences, 134(1), 1–21. https://doi.org/10.1016/j.jphs.2017.05.002

Halder, N., & Lal, G. (2021). Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.660342

Huang, Q., Liao, C., Ge, F., Ao, J., & Liu, T. (2022). Acetylcholine Bidirectionally Regulates Learning and Memory. Journal of Neurorestoratology, 10(2), 100002. https://doi.org/10.1016/j.jnrt.2022.100002

Indonesia, A. (2024). Alzheimer & Demensia. Alzheimer Indonesia.

Kandel, P., Semerci, F., & Mishra, R. (2022). Oleic Acid Is an Endogenous Ligand of TLX/NR2E1 That Triggers Hippocampal Neurogenesis. Proceedings of the National Academy of Sciences, 119(13). https://doi.org/10.1073/pnas.2023784119

Karoglu-Eravsar, E. T., Tuz-Sasik, M. U., & Karaduman, A. (2023). Long-Term Acetylcholinesterase Depletion Alters the Levels of Key Synaptic Proteins while Maintaining Neuronal Markers in the Aging Zebrafish (Danio rerio) Brain. Gerontology, 69(12), 1424–1436. https://doi.org/10.1159/000534343

Kezia, I., Erlina, L., Mudjihartini, N., & Fadilah, F. (2023). Molecular Simulation for Screening Bioactive Compounds as Potential Candidate for Alzheimer’s Disease. Eksakta: Berkala Ilmiah Bidang MIPA, 24, 179–192. https://doi.org/10.24036/eksakta/vol24-iss02/401

La Torre, M. E., Cianciulli, A., & Monda, V. (2023). α-Tocopherol Protects Lipopolysaccharide-Activated BV2 Microglia. Molecules, 28(8), 3340. https://doi.org/10.3390/molecules28083340

Lanctôt, K. L., Hviid Hahn-Pedersen, J., & Eichinger, C. S. (2023). Burden of Illness in People with Alzheimer’s Disease: A Systematic Review of Epidemiology, Comorbidities and Mortality. Journal of Prevention of Alzheimer’s Disease. https://doi.org/10.14283/JPAD.2023.61

Lee, K. H., Cha, M., & Lee, B. H. (2020). Neuroprotective Effect of Antioxidants in the Brain. International Journal of Molecular Sciences, 21(19), 7152. https://doi.org/10.3390/ijms21197152

Markowicz-Piasecka, M., Sikora, J., Szydłowska, A., Skupień, A., Mikiciuk-Olasik, E., & Huttunen, K. M. (2017). Metformin – A Future Therapy for Neurodegenerative Diseases. Pharmaceutical Research, 34(12), 2614–2627. https://doi.org/10.1007/s11095-017-2199-y

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

Moreira, N. C. dos S., Lima, J. E. B. de F., Marchiori, M. F., Carvalho, I., & Sakamoto-Hojo, E. T. (2022). Neuroprotective Effects of Cholinesterase Inhibitors: Current Scenario in Therapies for Alzheimer’s Disease and Future Perspectives. Journal of Alzheimer’s Disease Reports, 6(1), 177–193. https://doi.org/10.3233/ADR-210061

Nicole, S., Azuma, Y., Bauché, S., Eymard, B., Lochmüller, H., & Slater, C. (2017). Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions. Journal of Neuromuscular Diseases, 4(4), 269–284. https://doi.org/10.3233/JND-170257

Pebralia, J., Restianingsih, T., Sirait, Y., & Regina, I. (n.d.). Analisis Molekular Docking in Silico terhadap Bakteri Mycobacterium tuberculosis pada Daun Tanaman Herbal Eukaliptus Lemon (Corymbia citriodora).

Pharmacology and Physiology for Anesthesia. (2019). Elsevier. https://doi.org/10.1016/C2014-0-04139-1

Purnomo, V. C. M. R. (2021). Kajian Pustaka Efektivitas dan Efek Samping Donepezil pada Pasien Penderita Alzheimer.

Roda, A., Serra-Mir, G., Montoliu-Gaya, L., Tiessler, L., & Villegas, S. (2022). Amyloid-beta Peptide and Tau Protein Crosstalk in Alzheimer’s Disease. Neural Regeneration Research, 17(8), 1666. https://doi.org/10.4103/1673-5374.332127

Sakurai, K., Shen, C., Shiraishi, I., Inamura, N., & Hisatsune, T. (2021). Consumption of Oleic Acid on the Preservation of Cognitive Functions in Japanese Elderly Individuals. Nutrients, 13(2), 284. https://doi.org/10.3390/nu13020284

Turana, Y., Tengkawan, J., Suswanti, I., Suharya, D., Riyadina, W., & Pradono, J. (2019). Primary Prevention of Alzheimer’s Disease in Indonesia. International Journal of Aging Research. https://doi.org/10.28933/IJOAR-2019-06-2506

Wu, A., & Zhang, J. (2023). Neuroinflammation, Memory, and Depression: New Approaches to Hippocampal Neurogenesis. Journal of Neuroinflammation, 20(1), 283. https://doi.org/10.1186/s12974-023-02964-x