Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Research Article

In silico Evaluation of the Feasibility of Magnolia officinalis Electron-shuttling Compounds as Parkinson’s Disease Remedy

Author(s): Zaina Allyson Rivera, Lemmuel Tayo, Bor-Yann Chen and Po-Wei Tsai*

Volume 21, Issue 14, 2024

Published on: 16 October, 2023

Page: [3039 - 3048] Pages: 10

DOI: 10.2174/0115701808268549230919172444

Price: $65

Abstract

Background: Parkinson’s Disease is one of the leading neurodegenerative disorders in the world. Currently, there is still no treatment that could completely cure the disease. Traditional Chinese Medicine has been a source for drug candidates, and many studies have elucidated its pharmacokinetic capabilities. Previous studies showed that Magnolia officinalis has anti-inflammatory, antioxidant, and bioenergy generation activities. Furthermore, the electron-shuttling and bioenergy-stimulating capabilities of herbal and brain disorder medicines have been linked to their effectiveness as a remedy.

Objective: This preliminary study aims to evaluate the electron-shuttling compounds of Magnolia officinalis (i.e., acteoside, isoquercitrin, magnatriol B, obovatol, quercitrin, randaiol, and rutin) as potential drug candidates for Parkinson’s Disease.

Methods: The seven electron-shuttling compounds were individually docked to the five Parkinson’s Disease-related proteins, namely aromatic L-amino acid decarboxylase, α-synuclein, monoamine oxidase B, catechol-o-methyltransferase, and A2A adenosine receptor, using LibDock. ADMET predictions were also made to screen the compounds further.

Results: Molecular docking results showed that all compounds have relatively high LibDock scores against the proteins, with acteoside, isoquercitrin, and rutin having the highest scores. However, considering the ADMET results, only magnatriol B, obovatol, and randaiol had optimal properties as candidates for neurodegenerative drugs.

Conclusion: The electron-shuttling compounds of M. officinalis, magnatriol B, obovatol, and randaiol, have the potential to be a remedy for Parkinson’s Disease due to their high probability of binding to the proteins.

Keywords: Parkinson’s disease, Magnolia officinalis, magnatriol B, obovatol, randaiol, ADMET, neurodegenerative disorders (NDs).

« Previous Next »
Graphical Abstract

[1]
Mathur, S.; Gawas, C.; Ahmad, I.Z.; Wani, M.; Tabassum, H. Neurodegenerative disorders: Assessing the impact of natural vs drug‐induced treatment options. Aging Med., 2023, 6(1), 82-97.
[http://dx.doi.org/10.1002/agm2.12243] [PMID: 36911087]
[2]
Goyal, V.; Radhakrishnan, D.M. Parkinson’s disease: A review. Neurol. India, 2018, 66(S7), 26.
[http://dx.doi.org/10.4103/0028-3886.226451] [PMID: 29503325]
[3]
Hayes, M.T. Parkinson’s Disease and parkinsonism. Am. J. Med., 2019, 132(7), 802-807.
[http://dx.doi.org/10.1016/j.amjmed.2019.03.001] [PMID: 30890425]
[4]
Dugger, B.N.; Dickson, D.W. Pathology of neurodegenerative diseases. Cold Spring Harb. Perspect. Biol., 2017, 9(7), a028035.
[http://dx.doi.org/10.1101/cshperspect.a028035] [PMID: 28062563]
[5]
Kalia, L.V.; Lang, A.E. Parkinson’s disease. Lancet, 2015, 386(9996), 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081]
[6]
Elsworth, J.D. Parkinson’s disease treatment: Past, present, and future. J. Neural Transm., 2020, 127(5), 785-791.
[http://dx.doi.org/10.1007/s00702-020-02167-1] [PMID: 32172471]
[7]
Nagatsu, T.; Nakashima, A.; Watanabe, H.; Ito, S.; Wakamatsu, K. Neuromelanin in Parkinson’s Disease: Tyrosine hydroxylase and tyrosinase. Int. J. Mol. Sci., 2022, 23(8), 4176.
[http://dx.doi.org/10.3390/ijms23084176] [PMID: 35456994]
[8]
Nutt, J.G.; Curtze, C.; Hiller, A.; Anderson, S.; Larson, P.S.; Van Laar, A.D.; Richardson, R.M.; Thompson, M.E.; Sedkov, A.; Leinonen, M.; Ravina, B.; Bankiewicz, K.S.; Christine, C.W. Aromatic l‐amino acid decarboxylase gene therapy enhances levodopa response in parkinson’s disease. Mov. Disord., 2020, 35(5), 851-858.
[http://dx.doi.org/10.1002/mds.27993] [PMID: 32149427]
[9]
Edmondson, D.E.; Binda, C. Monoamine oxidases. In: Membrane Protein Complexes: Structure and Function; Springer, 2018; pp. 117-139.
[http://dx.doi.org/10.1007/978-981-10-7757-9_5]
[10]
Ramsay, R.R.; Albreht, A. Kinetics, mechanism, and inhibition of monoamine oxidase. J. Neural Transm., 2018, 125(11), 1659-1683.
[http://dx.doi.org/10.1007/s00702-018-1861-9] [PMID: 29516165]
[11]
Lin, C.H.; Fan, J.Y.; Lin, H.I.; Chang, C.W.; Wu, Y.R. Catechol-O-methyltransferase (COMT) genetic variants are associated with cognitive decline in patients with Parkinson’s disease. Parkinsonism Relat. Disord., 2018, 50, 48-53.
[http://dx.doi.org/10.1016/j.parkreldis.2018.02.015] [PMID: 29439855]
[12]
Tai, C-H.; Wu, R.M. Catechol-O-methyltransferase and Parkinson’s disease. Acta Med. Okayama, 2002, 56(1), 1-6.
[PMID: 11873938]
[13]
Salamon, A.; Zádori, D.; Szpisjak, L.; Klivényi, P.; Vécsei, L. What is the impact of catechol-O-methyltransferase (COMT) on Parkinson’s disease treatment? Expert Opin. Pharmacother., 2022, 23(10), 1123-1128.
[http://dx.doi.org/10.1080/14656566.2022.2060738] [PMID: 35373688]
[14]
Jenner, P.; Kanda, T.; Mori, A. How and why the adenosine A2A receptor became a target for Parkinson’s disease therapy. Int. Rev. Neurobiol., 2023.
[http://dx.doi.org/10.1016/bs.irn.2023.04.005]
[15]
Mori, A.; Chen, J.F.; Uchida, S.; Durlach, C.; King, S.M.; Jenner, P. The pharmacological potential of adenosine A2A receptor antagonists for treating Parkinson’s Disease. Molecules, 2022, 27(7), 2366.
[http://dx.doi.org/10.3390/molecules27072366] [PMID: 35408767]
[16]
Tsai, P.W.; Hsieh, C.Y.; Ting, J.U.; Ciou, Y.R.; Lee, C.J.; Hsieh, C.L.; Lien, T.K.; Hsueh, C.C.; Chen, B.Y. Synergistic deciphering of bioenergy production and electron transport characteristics to screen traditional Chinese medicine (TCM) for COVID-19 drug development. J. Taiwan Inst. Chem. Eng., 2022, 135, 104365.
[http://dx.doi.org/10.1016/j.jtice.2022.104365] [PMID: 35578714]
[17]
Chen, B.Y.; Lin, Y.H.; Wu, Y.C.; Hsueh, C.C. Deciphering electron-shuttling characteristics of neurotransmitters to stimulate bioelectricity-generating capabilities in microbial fuel cells. Appl. Biochem. Biotechnol., 2020, 191(1), 59-73.
[http://dx.doi.org/10.1007/s12010-020-03242-9] [PMID: 31989437]
[18]
Yuan, H.; Ma, Q.; Ye, L.; Piao, G. The traditional medicine and modern medicine from natural products. Molecules, 2016, 21(5), 559.
[http://dx.doi.org/10.3390/molecules21050559] [PMID: 27136524]
[19]
Tsai, P.W.; Mailem, R.C.; Tayo, L.L.; Hsueh, C.C.; Tseng, C.C.; Chen, B.Y. Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang. J. Taiwan Inst. Chem. Eng., 2023, 147, 104898.
[http://dx.doi.org/10.1016/j.jtice.2023.104898] [PMID: 37193294]
[20]
Poivre, M.; Duez, P. Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents. J. Zhejiang Univ. Sci. B, 2017, 18(3), 194-214.
[http://dx.doi.org/10.1631/jzus.B1600299] [PMID: 28271656]
[21]
Niu, L.; Hou, Y.; Jiang, M.; Bai, G. The rich pharmacological activities of Magnolia officinalis and secondary effects based on significant intestinal contributions. J. Ethnopharmacol., 2021, 281, 114524.
[http://dx.doi.org/10.1016/j.jep.2021.114524] [PMID: 34400262]
[22]
Boulaamane, Y.; Ibrahim, M.A.A.; Britel, M.R.; Maurady, A. In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA 2A R antagonists for the treatment of Parkinson’s disease. J. Integr. Bioinform., 2022, 19(4), 20210027.
[http://dx.doi.org/10.1515/jib-2021-0027] [PMID: 36112816]
[23]
Boyina, H.K.; Geethakhrishnan, S.L.; Panuganti, S.; Gangarapu, K.; Devarakonda, K.P.; Bakshi, V. In silico and in vivo studies on quercetin as potential anti-parkinson agent. Adv. Exp. Med. Biol., 2020, 1195, 1-11.
[http://dx.doi.org/10.1007/978-3-030-32633-3_1]
[24]
Gnanaraj, C.; Sekar, M.; Fuloria, S.; Swain, S.S.; Gan, S.H.; Chidambaram, K.; Rani, N.N.I.M.; Balan, T.; Stephenie, S.; Lum, P.T.; Jeyabalan, S.; Begum, M.Y.; Chandramohan, V.; Thangavelu, L.; Subramaniyan, V.; Fuloria, N.K. In silico molecular docking analysis of karanjin against alzheimer’s and parkinson’s diseases as a potential natural lead molecule for new drug design, development and therapy. Molecules, 2022, 27(9), 2834.
[http://dx.doi.org/10.3390/molecules27092834] [PMID: 35566187]
[25]
Xiong, G.; Wu, Z.; Yi, J.; Fu, L.; Yang, Z.; Hsieh, C.; Yin, M.; Zeng, X.; Wu, C.; Lu, A.; Chen, X.; Hou, T.; Cao, D. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res., 2021, 49(W1), W5-W14.
[http://dx.doi.org/10.1093/nar/gkab255] [PMID: 33893803]
[26]
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), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[27]
Chen, B.Y.; Wu, Y.C.; Lin, Y.H.; Tayo, L.L.; Tacas, A.C.; Hsueh, C.C. Deciphering electron-shuttling characteristics of parkinson’s disease medicines via bioenergy extraction in microbial fuel cells. Ind. Eng. Chem. Res., 2020, 59(39), 17124-17136.
[http://dx.doi.org/10.1021/acs.iecr.0c01062]
[28]
Abhishek, K.; Saksham, R.; Deepti, K.; Rao, N.G.R. R.; Surya, P.; Vinay, K.; Vidhu, S.; Priya, B. Medicinal plants and herbal formulations ameliorating neurodegeneration: Remedies combating parkinson’s and alzheimer’s disease. J. Young Pharm., 2023, 15(2), 194-200.
[http://dx.doi.org/10.5530/jyp.2023.15.28]
[29]
Chuang, D.Y.; Chan, M.H.; Zong, Y.; Sheng, W.; He, Y.; Jiang, J.H.; Simonyi, A.; Gu, Z.; Fritsche, K.L.; Cui, J.; Lee, J.C.; Folk, W.R.; Lubahn, D.B.; Sun, A.Y.; Sun, G.Y. Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells. J. Neuroinflammation, 2013, 10(1), 786.
[http://dx.doi.org/10.1186/1742-2094-10-15] [PMID: 23356518]
[30]
Boral, N.; Ghosh, P.; Goswami, A.; Bhattacharyya, M. Accountable Prediction of Drug ADMET Properties with Molecular Descriptors. bioRxiv, 2022.
[http://dx.doi.org/10.1101/2022.06.29.115436]
[31]
Mandlik, V.; Bejugam, P.R.; Singh, S. Application of artificial neural networks in modern drug discovery. In: Application of Artificial Neural Networks in Modern Drug Discovery; , 2016; pp. 123-139.
[http://dx.doi.org/10.1016/B978-0-12-801559-9.00006-5]
[32]
Steinmetz, K.L.; Spack, E.G. The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurol., 2009, 9(S1), S2.
[http://dx.doi.org/10.1186/1471-2377-9-S1-S2] [PMID: 19534731]
[33]
Dulsat, J.; López-Nieto, B.; Estrada-Tejedor, R.; Borrell, J.I. Evaluation of free online ADMET tools for academic or small biotech environments. Molecules, 2023, 28(2), 776.
[http://dx.doi.org/10.3390/molecules28020776] [PMID: 36677832]
[34]
Diller, D.J.; Merz, K.M., Jr High throughput docking for library design and library prioritization. Proteins, 2001, 43(2), 113-124.
[http://dx.doi.org/10.1002/1097-0134(20010501)43:2<113:AID-PROT1023>3.0.CO;2-T] [PMID: 11276081]
[35]
Alam, S.; Khan, F. Virtual screening, docking, ADMET and system pharmacology studies on garcinia caged xanthone derivatives for anticancer activity. Sci. Rep., 2018, 8(1), 5524.
[http://dx.doi.org/10.1038/s41598-018-23768-7] [PMID: 29615704]
[36]
Shen, C.C.; Ni, C.L.; Shen, Y.C.; Huang, Y.L.; Kuo, C.H.; Wu, T.S.; Chen, C.C. Phenolic constituents from the stem bark of Magnolia officinalis. J. Nat. Prod., 2009, 72(1), 168-171.
[http://dx.doi.org/10.1021/np800494e] [PMID: 19086868]
[37]
Choi, D.Y.; Lee, J.W.; Peng, J.; Lee, Y.J.; Han, J.Y.; Lee, Y.H.; Choi, I.S.; Han, S.B.; Jung, J.K.; Lee, W.S.; Lee, S.H.; Kwon, B.M.; Oh, K.W.; Hong, J.T. Obovatol improves cognitive functions in animal models for Alzheimer’s disease. J. Neurochem., 2012, 120(6)
[http://dx.doi.org/10.1111/j.1471-4159.2011.07642.x] [PMID: 22212065]
[38]
Bai, J. Effects of a potent antioxidant randaiol and its derivatives on ROS-induced cellular damage. Thesis Dissertations: Kyushu University,, 2018.

Rights & Permissions Print Cite
Article Metrics
6
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy