Neuroprotective Potential of Oleic Acid and Alpha Tocopherol on Memory Function: In-Silico Docking and ADMETox

Regita Herlianda Cahyani; Emni Purwoningsih; Luhu Avianto Tapiheru; Humairah Medina Liza Lubis

doi:10.55606/jurrike.v5i2.10263

Authors

Regita Herlianda Cahyani Universitas Muhammadiyah Sumatera Utara
Emni Purwoningsih Universitas Muhammadiyah Sumatera Utara
Luhu Avianto Tapiheru Universitas Muhammadiyah Sumatera Utara
Humairah Medina Liza Lubis Universitas Muhammadiyah Sumatera Utara

DOI:

https://doi.org/10.55606/jurrike.v5i2.10263

Keywords:

Alpha-Tocopherol, ADMETox, Brain-Derived Neurotrophic Factor (BDNF), Molecular Docking, Oleic Acid

Abstract

Decreased levels of brain-derived neurotrophic factor (BDNF) are closely related to neurodegenerative diseases such as Alzheimer's. This causes a decrease in cognitive function, memory and behavior due to a decrease in the BDNF protein which has the main function of protecting nerve growth, plasticity, nerve resilience, as well as being an important shield against nerve degeneration. Objective: of this research is to analyze the interaction between the oleic acid and alpha tocopherol ligands with the BDNF protein by molecular docking, as well as to analyze the ADMETox compounds of oleic acid and alpha tocopherol. Methods: This research is descriptive analytical. Molecular docking uses the Autodock tools, LigandScout, Discovery Studio, and Marvin Sketch applications. ADMETox analysis uses the SwissADME, ADMETlab 2.0, and ProTox-II sites. Results: the binding energy of oleic acid compounds to BDNF, TrkB, and CREB is -3.13 kcal/mol, -6.13 kcal/mol, and -3.70 kcal/mol. The binding energy results for alpha tocopherol compounds on BDNF, TrkB, and CREB are -5.67 kcal/mol, -8.04 kcal/mol, and -7.04 kcal/mol. ADMETox found that alpha tocopherol and oleic acid compounds fulfill Lipinski's rule of five and do not inhibit cytochrome P450 enzymes. Conclusion: Oleic acid and alpha tocopherol bind to BDNF, TrkB and CREB proteins and are safe for oral consumption.

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References

Boittier, E. D., Tang, Y. Y., Buckley, M. E., Schuurs, Z. P., Richard, D. J., & Gandhi, N. S. (2020). Assessing molecular docking tools to guide targeted drug discovery of CD38 inhibitors. International Journal of Molecular Sciences, 21(15), 1–19. https://doi.org/10.3390/ijms21155183

Boros, B. V., Dascalu, D., Ostafe, V., & Isvoran, A. (2022). Assessment of the effects of chitosan, chitooligosaccharides and their derivatives on Lemna minor. Molecules, 27(18). https://doi.org/10.3390/molecules27186123

Brunton, L. L., Dandan, R. H., & Knollmann, B. C. (2023). Goodman & Gilman’s: The pharmacological basis of therapeutics (14th ed.). McGraw-Hill Education.

Colucci-D’Amato, L., Speranza, L., & Volpicelli, F. (2020). Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. International Journal of Molecular Sciences, 21(20), 1–29. https://doi.org/10.3390/ijms21207777

Gao, L., Zhang, Y., Sterling, K., & Song, W. (2022). Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Translational Neurodegeneration, 11(1). https://doi.org/10.1186/s40035-022-00279-0

Huang, Y., He, C., Hu, Z., Chu, X., Zhou, S., Hu, X., Deng, J., Xiao, D., Tao, T., Yang, H., Chen, A. F., Yin, Y., & Yang, X. (2023). The beneficial effects of alpha-tocopherol on intestinal function and the expression of tight junction proteins in differentiated segments of the intestine in piglets. Food Science & Nutrition, 11(2), 677–687. https://doi.org/10.1002/fsn3.3103

Ionescu-Tucker, A., & Cotman, C. W. (2021). Emerging roles of oxidative stress in brain aging and Alzheimer’s disease. Neurobiology of Aging, 107, 86–95. https://doi.org/10.1016/j.neurobiolaging.2021.07.014

Jeon, S., Lee, C. H., Liu, Q. F., Kim, G. W., Koo, B. S., & Pak, S. C. (2014). Alteration in brain-derived neurotrophic factor (BDNF) after treatment of mice with herbal mixture containing Euphoria longana, Houttuynia cordata and Dioscorea japonica. DARU Journal of Pharmaceutical Sciences, 22(1). https://doi.org/10.1186/s40199-014-0077-2

Kadry, H., Noorani, B., & Cucullo, L. (2020). A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids and Barriers of the CNS, 17(1). https://doi.org/10.1186/s12987-020-00230-3

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

Marcelino, G., Hiane, P. A., Freitas, K. de C., Santana, L. F., Pott, A., Donadon, J. R., & Guimarães, R. de C. A. (2019). Effects of olive oil and its minor components on cardiovascular diseases, inflammation, and gut microbiota. Nutrients, 11(8). https://doi.org/10.3390/nu11081826

Mudjihartini, N. (2021). Brain-derived neurotrophic factor (BDNF) dan proses penuaan: Sebuah tinjauan. Jurnal Biomedika dan Kesehatan, 4(3), 120–129. https://doi.org/10.18051/JBiomedKes.2021.v4.120-129

Numakawa, T., & Odaka, H. (2022). The role of neurotrophin signaling in age-related cognitive decline and cognitive diseases. International Journal of Molecular Sciences, 23(14). https://doi.org/10.3390/ijms23147726

Nusantoro, Y. R., & Fadlan, A. (2020). Analisis sifat mirip obat, prediksi ADMET, dan penambatan molekular isatinil-2-aminobenzoilhidrazon dan kompleks logam transisi Co(II), Ni(II), Cu(II), Zn(II) terhadap BCL2-XL. Akta Kimia Indonesia, 5(2), 114. https://doi.org/10.12962/j25493736.v5i2.7881

Opo, F. A. D. M., Rahman, M. M., Ahammad, F., Ahmed, I., Bhuiyan, M. A., & Asiri, A. M. (2021). Structure-based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-83626-x

Ou, Z., Pan, J., Tang, S., Duan, D., Yu, D., Nong, H., & Wang, Z. (2021). Global trends in the incidence, prevalence, and years lived with disability of Parkinson’s disease in 204 countries/territories from 1990 to 2019. Frontiers in Public Health, 9. https://doi.org/10.3389/fpubh.2021.776847

Paulson, O. B. (2002). Blood-brain barrier, brain metabolism and cerebral blood flow. European Neuropsychopharmacology, 12, 495–501. https://doi.org/10.1016/S0924-977X(02)00098-6

Pinzi, L., & Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. International Journal of Molecular Sciences, 20(18). https://doi.org/10.3390/ijms20184331

Putra, A. M. J. (2016). Sifat-sifat substansi pangan fungsional yang aman. Indonesia Natural Research Pharmaceutical Journal, 1(1).

Renantha, R. R., Liga, A. R., Tanugroho, C. B., Denovian, L. X., Budiyanto, S. L. A. Z., & Parikesit, A. A. (2022). Flavonoids as potential inhibitors of dengue virus 2 (DENV2) envelope protein. Journal of Pharmacy and Pharmacognosy Research, 10(4), 660–675. https://doi.org/10.56499/jppres22.1375_10.4.660

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), 1–10. https://doi.org/10.3390/nu13020284

Salvatore, S. R., Vitturi, D. A., Fazzari, M., Jorkasky, D. K., & Schopfer, F. J. (2017). Evaluation of 10-nitro oleic acid bio-elimination in rats and humans. Scientific Reports, 7. https://doi.org/10.1038/srep39900

Shannon, M. W., Borron, S. W., & Burns, M. J. (2007). Haddad and Winchester’s clinical management of poisoning and drug overdose. Saunders.

Song, J., Kim, Y.-S., Lee, D. H., Lee, S. H., Park, H. J., Lee, D., & Kim, H. (2019). Neuroprotective effects of oleic acid in rodent models of cerebral ischaemia. Scientific Reports, 9(1), 10732. https://doi.org/10.1038/s41598-019-47057-z

Wang, D., Zheng, J., Sun, X., Xie, L., & Yang, Y. (2024). Study on the pharmacological mechanism of icariin for the treatment of Alzheimer’s disease based on network pharmacology and molecular docking techniques. Metabolites, 14(1). https://doi.org/10.3390/metabo14010001

Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., Huai, C., Shen, L., Zhang, N., He, L., & Qin, S. (2021). Cytochrome P450 enzymes and drug metabolism in humans. International Journal of Molecular Sciences, 22(23). https://doi.org/10.3390/ijms222312808