INVESTIGATING MULTITARGET POTENTIAL OF MUCUNA PRURIENS AGAINST PARKINSON'S DISEASE: INSIGHTS FROM MOLECULAR DOCKING, MMGBSA, PHARMACOPHORE MODELING, MD SIMULATIONS AND ADMET ANALYSIS
Computational Intervention of Mucuna Pruriens: Investigating its Multitarget Potential Against Parkinson's Disease
DOI:
https://doi.org/10.22159/ijap.2024v16i5.51474Keywords:
Mucuna pruriens, Multitarget, Molecular docking, Pharmacophore modeling, Molecular dynamic simulation, Luteolin, Acacetin, Parkinsons diseaseAbstract
Objective
Mucuna pruriens (Velvet beans) is a leguminous plant recognised in Vedic therapy as an anti-Parkinsonism agent. The plant is known as natural reservoir for levodopa. The aim of the study is to evaluate the multitarget inhibitory potency of active constituents present in Mucuna pruriens using in silico tools.
Method
The phytoconstituents present in Mucuna pruriens were retrieved from the IMPPAT database. The inhibitory potential of phytoconstituents against monoamine Oxidase-B (MAO-B), acetylcholine esterase (AChE) and Catechol-O-methyltransferase (COMT) enzymes were evaluated using in silico approaches like molecular docking, pharmacophore modelling, and molecular dynamics were studied using Schrödinger software programs. The physicochemical and toxicity parameters were evaluated using Qikprop and ProTox-3.
Results
The molecular docking studies revealed the phytoconstituent luteolin and acacetin showed promising multitargeted inhibitory property. Especially luteolin (-11.504 Kcal/mol) and acacetin (-10.620 Kcal/mol) has obtained excellent docking scores with MAO-B, whereas the known drug L-dopa showed docking score of -8.501 Kcal/mol. The pharmacophore modeling revealed that donor, acceptor and aromatic features present in luteolin and acacetin are the essential pharmacophoric features accountable for biological activity. The simulation study generated the stability of the protein-ligand complex and found that luteolin showed a stable complex with MAO-B. The active constituents comply with Lipinski’s rule for drug-likeness.
Conclusion
Based on these findings, the result of the current study can be used to develop a novel luteolin-based drug for treating Parkinson’s disease with preferred structural modification. However, additional and more comprehensive research is required on this compound.
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References
Ouachinou JA, Dassou GH, Idohou R, Adomou AC, Yédomonhan H. National inventory and usage of plant-based medicine to treat gastrointestinal disorders with cattle in Benin (West Africa). South African Journal of Botany. 2019;122:432-46.
Rai SN, Chaturvedi VK, Singh P, Singh BK, Singh MP. Mucuna pruriens in Parkinson’s and in some other diseases: recent advancement and future prospective. 3 Biotech. 2020;10:1-1.
Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G. The magic velvet bean of Mucuna pruriens. J Tradit Complement Med 2 (4): 331–339.
Martínez‐Leo EE, Martín‐Ortega AM, Acevedo‐Fernández JJ, Moo‐Puc R, Segura‐Campos MR. Peptides from Mucuna pruriens L., with protection and antioxidant in vitro effect on HeLa cell line. Journal of the Science of Food and Agriculture. 2019;99(8):4167-73.
Guerranti R, Ogueli IG, Bertocci E, Muzzi C, Aguiyi JC, Cianti R, Armini A, Bini L, Leoncini R, Marinello E, Pagani R. Proteomic analysis of the pathophysiological process involved in the antisnake venom effect of Mucuna pruriens extract. Proteomics. 2008;8(2):402-12.
Manyam BV, Dhanasekaran M, Hare TA. Neuroprotective effects of the antiparkinson drug Mucuna pruriens. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2004;18(9):706-12.
Majekodunmi SO, Oyagbemi AA, Umukoro S, Odeku OA. Evaluation of the anti–diabetic properties of Mucuna pruriens seed extract. Asian Pacific Journal of Tropical Medicine. 2011;4(8):632-6.
Golbabapour S, Hajrezaie M, Hassandarvish P, Abdul Majid N, Hadi AH, Nordin N, Abdulla MA. Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats. BioMed Research International. 2013;2013.
Avoseh ON, Ogunwande IA, Ojenike GO, Mtunzi FM. Volatile composition, toxicity, analgesic, and anti-inflammatory activities of Mucuna pruriens. Natural Product Communications. 2020;15(7):1934578X20932326.
OA U, Okpashi VE, Azuaga TI, Iyen SI, Aikhoje EF, Lajaka JI. Phytochemical screening and antimicrobial activities of leaf extracts of mucuna pruriens. Journal of Pharmaceutical & Allied Sciences. 2019;16(4).
Menon S, Agarwal H, Rajeshkumar S, Kumar SV. Anticancer assessment of biosynthesized silver nanoparticles using Mucuna pruriens seed extract on Lung Cancer Treatment. Research Journal of Pharmacy and Technology. 2018;11(9):3887-91.
Suresh S, Prakash S. Effect of Mucuna pruriens (Linn.) on sexual behavior and sperm parameters in streptozotocin-induced diabetic male rat. The journal of sexual medicine. 2012;9(12):3066-78.
Pulikkalpura H, Kurup R, Mathew PJ, Baby S. Levodopa in Mucuna pruriens and its degradation. Scientific reports. 2015;5(1):11078.
Wakabayashi K, Tanji K, Mori F, Takahashi H. The Lewy body in Parkinson's disease: molecules implicated in the formation and degradation of α‐synuclein aggregates. Neuropathology. 2007;27(5):494-506.
Michalska P, León R. When it comes to an end: oxidative stress crosstalk with protein aggregation and neuroinflammation induce neurodegeneration. Antioxidants. 2020;9(8):740.
Mishra AK, Dixit A. Dopaminergic axons: key recitalists in Parkinson’s disease. Neurochemical Research. 2022;47(2):234-48.
Cheong SL, Federico S, Spalluto G, Klotz KN, Pastorin G. The current status of pharmacotherapy for the treatment of Parkinson’s disease: transition from single-target to multitarget therapy. Drug discovery today. 2019;24(9):1769-83.
Mathew B, Parambi DG, Mathew GE, Uddin MS, Inasu ST, Kim H, Marathakam A, Unnikrishnan MK, Carradori S. Emerging therapeutic potentials of dual‐acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Archiv der Pharmazie. 2019;352(11):1900177.
Morphy R, Rankovic Z. Designed multiple ligands. An emerging drug discovery paradigm. Journal of medicinal chemistry. 2005;48(21):6523-43.
Alov P, Stoimenov H, Lessigiarska I, Pencheva T, Tzvetkov NT, Pajeva I, Tsakovska I. In Silico Identification of Multi-Target Ligands as Promising Hit Compounds for Neurodegenerative Diseases Drug Development. International Journal of Molecular Sciences.2022;23(21):13650.
James JP, Aiswarya TC, Priya SN, Jyothi DI, Dixit SR. Structure based multitargeted molecular docking analysis of pyrazole-condensed heterocyclics against lung cancer. Int. J. App. Pharm. 2021;3(6):157-69.
Otieno F, Kagia R. Virtual screening for chemical analogues similar to phytochemicals that inhibit aldose reductase in the development of diabetic microvascular complications. F1000Research. 2023;12(314):314.
James JP, Jouhara M, Fathima ZC, D’Souza RR. Green synthesis, multitargeted molecular docking and ADMET studies of chalcones based scaffold as anti-breast cancer agents. Res J Pharm Technol. 2023;16(5):2215-22.
Suwardi S, Salim A, Mahendra JA, Wijayanto DB, Rochiman NA, Anam SK, Hikmah N. Virtual Screening, Pharmacokinetic Prediction, Molecular Docking and Dynamics Approaches in the Search for Selective and Potent Natural Molecular Inhibitors of MAO-B for the Treatment of Neurodegenerative Diseases. Indonesian Journal of Chemistry and Environment. 2023;6(2).
Hosen ME, Rahman MS, Faruqe MO, Khalekuzzaman M, Islam MA, Acharjee UK, Zaman R. Molecular docking and dynamics simulation approach of Camellia sinensis leaf extract derived compounds as potential cholinesterase inhibitors. In Silico Pharmacology. 2023;11(1):14.
Patel CN, Georrge JJ, Modi KM, Narechania MB, Patel DP, Gonzalez FJ, Pandya HA. Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer’s disease. Journal of Biomolecular Structure and Dynamics. 2018;36(15):3938-57.
James JP, Jyothi D, Priya S. In silico screening of phytoconstituents with antiviral activities against SARS-COV-2 main protease, Nsp12 polymerase, and Nsp13 helicase proteins. Lett Drug Des Discov. 2021; 18(8):841-57. Doi: https://doi.org/10.2174/1570180818666210317162502
Mateev E, Georgieva M, Zlatkov A. Improved Molecular Docking of MAO-B Inhibitors with Glide. Biointerface Res App Chem. 2022; 13:159. https://doi.org/10.33263/BRIAC132.159
P. James J, Ishwar Bhat K, More UA, Joshi SD. Design, synthesis, molecular modeling, and ADMET studies of some pyrazoline derivatives as shikimate kinase inhibitors. Med Chem Res. 2018; 27:546-59. Doi: 10.1007/s00044-017-2081-9
Malkaje S, Srinivasa MG, Deshpande N, Navada S, Revanasiddappa BC. An In-silico Approach: Design, Homology Modeling, Molecular Docking, MM/GBSA Simulations, and ADMET Screening of Novel 1, 3, 4-oxadiazoles as PLK1inhibitors. Curr Drug Res Rev. 2023;15(1):88-100. Doi: https://doi.org/10.2174/2589977514666220821203739
Oluyori AP, Olanipekun BE, Adeyemi OS, Egharevba GO, Adegboyega AE, Oladeji OS. Molecular docking, pharmacophore modelling, MD simulation and in silico ADMET study reveals bitter cola constituents as potential inhibitors of SARS-CoV-2 main protease and RNA dependent-RNA polymerase. J Biomol Struct Dyn. 2023; 41(4):1510-25. Doi: https://doi.org/10.1007/s43440-021-00252-0
Lagunin A, Filimonov D, Poroikov V. Multi-targeted natural products evaluation based on biological activity prediction with PASS. Current Pharmaceutical Design. 2010;16(15):1703-17.
T. S P, P. James J, SR Dwivedi P, Priya S, Fathima C Z, T. J S. Synthesis, Molecular Docking and Molecular Dynamic Studies of Thiazolidineones as Acetylcholinesterase and Butyrylcholinesterase Inhibitors. Polycycl Aromat Compd. 2023:1-21. Doi: https://doi.org/10.1080/10406638.2023.2233666
James JP, Aziz AA, Krishnan D, Kumar P, Kumar A. Molecular docking and pharmacophore modelling of phytoconstituents of vaccinium secundiflorum for antidiabetic and antioxidant activity. Int J Comput Biol Drug Des. 2021; 14(5):315-42. Doi: https://doi.org/10.1504/IJCBDD.2021.120122
James JP, Devaraji V, Sasidharan P, Pavan TS. Pharmacophore Modeling, 3D QSAR, Molecular Dynamics Studies and Virtual Screening on Pyrazolopyrimidines as anti-Breast Cancer Agents. Polycycl. Aromat. Compd. 2023;43(8):7456-73. Do https://doi.org/10.1080/10406638.2022.2135545
QikProp S. LLC. New York; NY. 2019
Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic acids research. 2018;46(W1):W257-63.
Patel S, Modi P, Chhabria M. Rational approach to identify newer caspase-1 inhibitors using pharmacophore based virtual screening, docking and molecular dynamic simulation studies. J Mol Graph Model. 2018; 81:106-15. Doi: https://doi.org/10.1016/j.jmgm.2018.02.017
Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskii DS, Pogodin PV, Poroikov VV. Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chem. Heterocycl. Compd. 2014; 50:444-57. Doi: https://doi.org/10.1007/s10593-014-1496-1
Daina A, Michielin O, Zoete V. Swiss Target Prediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic acids research. 2019;47(W1):W357-64.
Goldenberg MM. Medical management of Parkinson’s disease. Pharmacy and Therapeutics. 2008;33(10):590.
Rai SN, Birla H, Singh SS, Zahra W, Patil RR, Jadhav JP, Gedda MR, Singh SP. Mucuna pruriens protects against MPTP intoxicated neuroinflammation in Parkinson’s disease through NF-κB/pAKT signaling pathways. Frontiers in Aging Neuroscience. 2017;9:421.
Prakash J, Chouhan S, Yadav SK, Westfall S, Rai SN, Singh SP. Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons. Neurochemical Research. 2014;39:2527-36.
Birla H, Rai SN, Singh SS, Zahra W, Rawat A, Tiwari N, Singh RK, Pathak A, Singh SP. Tinospora cordifolia suppresses neuroinflammation in parkinsonian mouse model. Neuromolecular medicine. 2019;21:42-53.
Siddique YH. Role of luteolin in overcoming Parkinson's disease. Biofactors. 2021;47(2):198-206
Ha SK, Moon E, Lee P, Ryu JH, Oh MS, Kim SY. Acacetin attenuates neuroinflammation via regulation the response to LPS stimuli in vitro and in vivo. Neurochemical research. 2012;37:1560-7.
Siddique YH, Jyoti S, Naz F. Protective effect of luteolin on the transgenic Drosophila model of Parkinson's disease. Brazil J Pharma Sci. 2018;54(3):1–13.
Huang L, Kim MY, Cho JY. Immunopharmacological activities of luteolin in chronic diseases. International Journal of Molecular Sciences. 2023;24(3):2136.
Elmazoglu, Z.; Yar Saglam, A.S.; Sonmez, C.; Karasu, C. Luteolin Protects Microglia against Rotenone-Induced Toxicity in a Hormetic Manner through Targeting Oxidative Stress Response, Genes Associated with Parkinson’s Disease and Inflammatory Pathways. Drug Chem. Toxicol. 2020, 43, 96–103.
Siracusa R, Paterniti I, Impellizzeri D, Cordaro M, Crupi R, Navarra M, Cuzzocrea S, Esposito E. The association of palmitoylethanolamide with luteolin decreases neuroinflammation and stimulates autophagy in Parkinson’s disease model. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2015;14(10):1350-66.
Reudhabibadh, R.; Binlateh, T.; Chonpathompikunlert, P.; Nonpanya, N.; Prommeenate, P.; Chanvorachote, P.; Hutamekalin, P. Suppressing Cdk5 Activity by Luteolin Inhibits MPP+-Induced Apoptotic of Neuroblastoma through Erk/Drp1 and Fak/Akt/GSK3 Pathways. Molecules 2021, 26, 1307.
Ha SK, Moon E, Lee P, Ryu JH, Oh MS, Kim SY. Acacetin attenuates neuroinflammation via regulation the response to LPS stimuli in vitro and in vivo. Neurochemical research. 2012;37:1560-7.
Bu J, Shi S, Wang HQ, Niu XS, Zhao ZF, Wu WD, Zhang XL, Ma Z, Zhang YJ, Zhang H, Zhu Y. Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway. Neural Regeneration Research. 2019;14(4):605-12.
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