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International Journal of Molecular Biotechnological Research Original Research

Exploring the Therapeutic Potential of Grapeseed Phytoconstituent Through Molecular Docking Analysis for Multiple System Atrophy Treatment

  1. Fatima Abdul Azeez Student, Department of Biotechnology, Mar Athanasius College, Kothamangalam

Abstract

Objective: Alpha-synuclein (α-Syn) aggregates are a common neurodegenerative disorder associated with Parkinson’s disease and multiple system atrophy (MSA). As a fruit that is extensively grown, grapes have several pharmacological advantages when it comes to reducing oxidative stress. Research has indicated that grape seed phytoconstituents have a major effect on α-Syn. The objective of this study is to inquire into the pharmacological characteristics and potential therapeutic applications of grape seed derivatives against the targeted protein, α-Syn.

Methods: To assess their binding affinity with α-Syn, thirty distinct grape seed components and their phytoconstituents were chosen for this investigation. The PyRx virtual tool was employed for molecular docking processes, utilizing computational analysis based on the molecular structures of both phytocompounds and α-Syn. The protein structure was verified using a collection of tools, such as the PDBsum generator and BIOVIA Discovery studio program. Furthermore, ADMET filters were used to evaluate the ligands pharmacologically.

Result: The molecular docking studies indicated that thiamine, the ligand, had a low binding affinity for the protein α-Syn, which was the target.

Conclusion: As thiamine has been shown to be a therapeutic agent against α-Syn in Parkinson’s disease research, it may be a good choice for MSA and can be utilized to lessen its effects. To validate these results, in vitro studies are still necessary

Keywords

References (39)

  1. Sakakibara R. Multiple System Atrophy. Neurourology. 2019:549-562. doi:10.1007/978-94-017-7509-0_65
  2. Herrera‐Vaquero M, Heras‐Garvin A, Krismer F, Deleanu R, Boesch S, Wenning GK, et al. Signs of early cellular dysfunction in multiple system atrophy. Neuropathology and Applied Neurobiology. 2020;47(2):268-282. doi:10.1111/nan.12661
  3. Dickson DW, Liu WK, Hardy J, Farrer M, Mehta N, Uitti R, et al. Widespread Alterations of α-Synuclein in Multiple System Atrophy. The American Journal of Pathology. 1999;155(4):1241-1251. doi:10.1016/s0002-9440(10)65226-1
  4. Campese N, Fanciulli A, Stefanova N, Haybaeck J, Kiechl S, Wenning GK. Neuropathology of multiple system atrophy: Kurt Jellinger`s legacy. Journal of Neural Transmission. 2021;128(10):1481-1494. doi:10.1007/s00702-021-02383-3
  5. Kaplan S, Xie H, Wang J. Estimating the prevalence and incidence of multiple system atrophy in the USA: Insights from a national claims database. Parkinsonism & Related Disorders. 2023;117:105920. doi:10.1016/j.parkreldis.2023.105920
  6. Jellinger KA. Multiple system atrophy - a clinicopathological update. Free Neuropathol. 2020;1:1–17. doi:10.17879/freeneuropathology-2020-2813.
  7. Fitzgerald E, Murphy S, Martinson HA. Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson’s Disease. Frontiers in Neuroscience. 2019;13. doi:10.3389/fnins.2019.00369
  8. Srinivasan E, Chandrasekhar G, Chandrasekar P, Anbarasu K, Vickram AS, Karunakaran R, et al. Alpha-Synuclein Aggregation in Parkinson's Disease. Frontiers in Medicine. 2021;8. doi:10.3389/fmed.2021.736978
  9. Stefanova N, Bücke P, Duerr S, Wenning GK. Multiple system atrophy: an update. The Lancet Neurology. 2009;8(12):1172-1178. doi:10.1016/s1474-4422(09)70288-1
  10. Compagnoni GM, Fonzo AD. Understanding the pathogenesis of multiple system atrophy: state of the art and future perspectives. Acta Neuropathol Commun. 2019;7(1):113. doi:10.1186/s40478-019-0730-6.01
  11. Lee HJ, Ricarte D, Ortiz D, Lee SJ. Models of multiple system atrophy. Experimental & Molecular Medicine. 2019;51(11):1-10. doi:10.1038/s12276-019-0346-8
  12. Koga S, Dickson DW. Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy. Journal of Neurology, Neurosurgery & Psychiatry. 2017;89(2):175-184. doi:10.1136/jnnp-2017-315813
  13. Yazawa I, Giasson BI, Sasaki R, Zhang B, Joyce S, Uryu K, et al. Mouse Model of Multiple System Atrophy α-Synuclein Expression in Oligodendrocytes Causes Glial and Neuronal Degeneration. Neuron. 2005;45(6):847-859. doi:10.1016/j.neuron.2005.01.032
  14. Farooqui AA, Farooqui T, Madan A, Ong JHJ, Ong WY. Ayurvedic Medicine for the Treatment of Dementia: Mechanistic Aspects. Evidence-Based Complementary and Alternative Medicine. 2018;2018(1). doi:10.1155/2018/2481076
  15. Kumar S, Dobos GJ, Rampp T. The Significance of Ayurvedic Medicinal Plants. Journal of Evidence-Based Complementary & Alternative Medicine. 2016;22(3):494-501. doi:10.1177/2156587216671392
  16. Chavan SS, Kesari M. Trust-(Copyright-2022) [Online]. 2022;1. Maharatta. 2022. Available from: www.mahratta.org.
  17. Caetano SSP, Dias MDME, Sobreira ACF, Barroso AB, Pinheiro-Sant’Ana HM, Lucia CMD, et al. Characterization and bioactive compounds of organic Bordeaux grape seed oil and flours (Vitis labrusca L.). Research, Society and Development. 2022;11(14):e55111435888. doi:10.33448/rsd-v11i14.35888
  18. Garavaglia J, Markoski MM, Oliveira A, Marcadenti A. Grape Seed Oil Compounds: Biological and Chemical Actions for Health. Nutrition and Metabolic Insights. 2016;9. doi:10.4137/nmi.s32910
  19. Gupta M, Dey S, Marbaniang D, Pal P, Ray S, Mazumder B. Grape seed extract: having a potential health benefits. Journal of Food Science and Technology. 2019;57(4):1205-1215. doi:10.1007/s13197-019-04113-w
  20. Hey G, Nair N, Klann E, Gurrala A, Safarpour D, Mai V, et al. Therapies for Parkinson’s disease and the gut microbiome: evidence for bidirectional connection. Frontiers in Aging Neuroscience. 2023;15. doi:10.3389/fnagi.2023.1151850
  21. Fandy SJ. GRAPE SEED EXTRACT’S NEUROPROTECTIVE EFFECT AND PARKINSON’S DISEASE: A SYSTEMATIC REVIEW. MNJ (Malang Neurology Journal). 2022;9(1):44-51. doi:10.21776/ub.mnj.2023.009.01.9
  22. Polegato BF, Pereira AG, Azevedo PS, Costa NA, Zornoff LAM, Paiva SAR, et al. Role of Thiamin in Health and Disease. Nutrition in Clinical Practice. 2019;34(4):558-564. doi:10.1002/ncp.10234
  23. Costantini A, Pala MI, Grossi E, Mondonico S, Cardelli LE, Jenner C, et al. Long-Term Treatment with High-Dose Thiamine in Parkinson Disease: An Open-Label Pilot Study. The Journal of Alternative and Complementary Medicine. 2015;21(12):740-747. doi:10.1089/acm.2014.0353
  24. Lương KVQ, Nguyễn LTH. The Beneficial Role of Thiamine in Parkinson Disease. CNS Neuroscience & Therapeutics. 2013;19(7):461-468. doi:10.1111/cns.12078
  25. Rai SN, Singh P, Steinbusch HWM, Vamanu E, Ashraf G, Singh MP. The Role of Vitamins in Neurodegenerative Disease: An Update. Biomedicines. 2021;9(10):1284. doi:10.3390/biomedicines9101284
  26. Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, Chand RPB, Aparna SR, Mangalapandi P, et al. IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry And Therapeutics. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-22631-z
  27. Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, et al. PubChem Substance and Compound databases. Nucleic Acids Research. 2015;44(D1):D1202-D1213. doi:10.1093/nar/gkv951
  28. Tripathi P, Ghosh S, Talapatra SN. Bioavailability prediction of phytochemicals present in Calotropis procera (Aiton) R. Br. by using Swiss-ADME tool. World Sci News. 2019;131:147–163.
  29. Ivanović V, Rančić M, Arsić B, Pavlović A. Lipinski’s rule of five, famous extensions and famous exceptions. Chemia Naissensis. 2020;3(1):171–177.
  30. Prasanna S, Doerksen R. Topological Polar Surface Area: A Useful Descriptor in 2D-QSAR. Current Medicinal Chemistry. 2009;16(1):21-41. doi:10.2174/092986709787002817
  31. Chandrasekaran B, Abed SN, Al-Attraqchi O, Kuche K, Tekade RK. Computer-Aided Prediction of Pharmacokinetic (ADMET) Properties. Dosage Form Design Parameters. 2018:731-755. doi:10.1016/b978-0-12-814421-3.00021-x
  32. Rani N, Khare N, Jha AK. Molecular docking study of dihydrohelenalin against DNMT1 to treat oral cancer. Int J Res Anal Rev. 2020;7(3):427–437.
  33. Hollingsworth SA, Karplus PA. A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. bmc. 2010;1(3-4):271-283. doi:10.1515/bmc.2010.022
  34. Kumar P, Arya A. Ramachandran plot-A simplified approach [Online]. Available from: net/profile/Pranav-Kumar36/publication/330158666_Ramachandran_plot_A_simplified_approach/links/5c304d76458515a4c70d377b/Ramachandran-plot-A-simplified-approach.pdf.
  35. Laskowski RA. Enhancing the functional annotation of PDB structures in PDBsum using key figures extracted from the literature. Bioinformatics. 2007;23(14):1824-1827. doi:10.1093/bioinformatics/btm085
  36. Pawar RP, Rohane SH. Role of autodock vina in PyRx molecular docking. Asian J. Res Chem. 2021;14(2):132–134. doi:10.5958/0974-4150.2021.00024.9.
  37. Agarwal S, Mehrotra R. An overview of molecular docking. JSM Chem. 2016;49(2):1024.
  38. Tahir M, Baharuddin M, Najib A. In silico screening of brotowali (Tinospora crispa L.) chemical compounds as α-glucosidase inhibitor using the pyrx program. AIP Conference Proceedings. 2023;2731:050009. doi:10.1063/5.0123693
  39. Valdinocci D, Radford RAW, Goulding M, Hayashi J, Chung RS, Pountney DL. Extracellular Interactions of Alpha-Synuclein in Multiple System Atrophy. International Journal of Molecular Sciences. 2018;19(12):4129. doi:10.3390/ijms19124129