Antineuroinflammatory Properties of Compounds from Ethyl Acetate Fraction of Marsilea crenata C. Presl. Against Toll-Like Receptor 2 (3A7B) In Silico

  • Burhan Ma’arif Universitas Islam Negeri Maulana Malik Ibrahim Malang http://orcid.org/0000-0001-9182-343X
  • Reyhan Rahma Samudra Universitas Islam Negeri Maulana Malik Ibrahim Malang
  • Faisal Akhmal Muslikh Universitas Airlangga http://orcid.org/0000-0002-9611-7937
  • Tanaya Jati Dharma Dewi Universitas Islam Negeri Maulana Malik Ibrahim Malang
  • Luthfi Ahmad Muchlasi Universitas Islam Negeri Maulana Malik Ibrahim Malang

Abstract

Parkinson's disease (PD) can be triggered by overactive TLR2 due to α-synuclein abnormalities and aggregation. Marsilea crenata C. Presl. leaves inhibit neuroinflammatory progression. This study aimed to predict the antineuroinflammatory activity of M. crenata leaves with TLR2 (ID 3A7B) in an in silico study. The list of chemicals was collected through metabolite profiling with UPLC-QToF MS/MS, then analyzed for physicochemical properties using SwissADME and toxicity using the ProTox II online program. This analysis confirmed the molecule's safety for therapeutic use. ChemDraw 12.0 was used to build metabolite-profiled compounds. Avogadro 1.2.0 was utilized to optimize geometry, while PyRx 0.8 was used for Autodock Vina molecular docking. Agonist-TLR2 interactions were examined using docking results from Biovia Discovery Studio 2021. Tethering is valid; the program can be used because the RMSD is less than 2. The results showed that 6 of the 84 metabolite-profiled compounds were antagonistic to 3A7B and shared similar pharmacophore distances and amino acid linkages with N-acetyl-D-glucosamine, a native ligand of 3A7B. By binding to TLR2, the compounds from the ethyl acetate fraction of M. crenata leaves may potentially inhibit PD progression.

Author Biographies

Burhan Ma’arif, Universitas Islam Negeri Maulana Malik Ibrahim Malang

Department of Pharmacy, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jalan Locari, Tlekung, Junrejo, Batu, 65151, Indonesia; +6281335555725

Reyhan Rahma Samudra, Universitas Islam Negeri Maulana Malik Ibrahim Malang

Department of Pharmacy, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jalan Locari, Tlekung, Junrejo, Batu, 65151, Indonesia

Faisal Akhmal Muslikh, Universitas Airlangga

Department of Pharmacy, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jalan Locari, Tlekung, Junrejo, Batu, 65151, Indonesia

Tanaya Jati Dharma Dewi, Universitas Islam Negeri Maulana Malik Ibrahim Malang

Department of Pharmacy, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jalan Locari, Tlekung, Junrejo, Batu, 65151, Indonesia

Luthfi Ahmad Muchlasi, Universitas Islam Negeri Maulana Malik Ibrahim Malang

Department of Pharmacy, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jalan Locari, Tlekung, Junrejo, Batu, 65151, Indonesia

References

Balestrino, R. & Schapira, A. H. V. (2020). Parkinson Disease. European Journal of Neurology, 27(1), 27-42. https://doi.org/10.1111/ene.14108
Borrello, S., Nicolò, C., Delogu, G., Pandolfi, F., & Ria, F. (2011). TLR2: A Crossroads Between Infections and Autoimmunity? International Journal of Immunopathology and Pharmacology, 24(3), 549–556. https://doi.org/10.1177/039463201102400301
Cario, E. (2008). Barrier-Protective Function of Intestinal Epithelial Toll-Like Receptor 2. Mucosal Immunology, 1, S62–S66. https://doi.org/10.1038/mi.2008.47
Chen, W. W., Zhang, X., & Huang, W. J. (2016). Role of Neuroinflammation in Neurodegenerative Diseases (Review). Molecular Medicine Reports, 13(4), 3391–3396. https://doi.org/10.3892/mmr.2016.4948
Cherry, J., Olschowka, J., & O’Banion, K. (2014). Neuroinflammation and M2 Microglia: The Good, The Bad, and The Inflamed. Journal of Neuroinflammation, 11, 98. https://doi.org/10.1186/1742-2094-11-98
Cui, L., Zahedi, P., Saraceno, J., Bristow, R., Jaffray, D., & Allen, C. (2013). Neoplastic Cell Response to Tiopronin-Coated Gold Nanoparticles. Nanomedicine: Nanotechnology, Biology, and Medicine, 9(2), 264-273. https://doi.org/10.1016/j.nano.2012.05.016
Dzamko, N., Gysbers, A., Perera, G., Bahar, A., Shankar, A., Gao, J., et al. (2017). Toll-Like Receptor 2 is Increased in Neurons in Parkinson’s Disease Brain and May Contribute to Alpha-Synuclein Pathology. Acta Neuropathologica, 133(2), 303–319. https://doi.org/10.1007/s00401-016-1648-8
Ekins, S., Mestres, J., & Testa, B. (2007). In silico Pharmacology for Drug Discovery: Applications to Targets and Beyond. British Journal of Pharmacology, 152(1), 21-37. https://doi.org/10.1038/sj.bjp.0707306
Engler-Chiurazzi, E. B., Brown, C. M., Povroznik, J. M., & Simpkins, J. W. (2017). Estrogens as Neuroprotectants: Estrogenic Actions in the Context of Cognitive Aging and Brain Injury. Progress in Neurobiology, 157, 188-211. https://doi.org/10.1016/j.pneurobio.2015.12.008
Ferreira, L., Santos, R., Glaucius, O., & Andricopulo, A. (2015). Molecular Docking and Structure-Based Drug Design Strategies. Molecules, 20(7), 13384-13421. https://doi.org/10.3390/molecules200713384
Gao, W., Xiong, Y., Li, Q., & Yang, H. (2017). Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics. Frontiers in Physiology, 8, 508. https://doi.org/10.3389/fphys.2017.00508
Gelosa, P., Colazzo, F., Tremoli, E., Sironi, L., & Castiglioni, L. (2017). Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases. Mediators of Inflammation, 2017, 3454212. https://doi.org/10.1155/2017/3454212
Hwang, S. Y., Shin, J. H., Hwang, J. S., Kim, S. Y., Shin, J. A., Oh, E. S., et al. (2010). Glucosamine Exerts A Neuroprotective Effect Via Suppression of Inflammation in Rat Brain Ischemia/Reperfusion Injury. Glia, 58(15), 1881–1892. https://doi.org/10.1002/glia.21058
Kwon, S., Iba, M., Masliah, E., & Kim, C. (2019). Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies. Experimental Neurobiology, 28(5), 547–553. https://doi.org/10.5607/en.2019.28.5.547
Lewis, P. A. & Spillane J. E. (2018). Neurodegenerative Disease 1st edition. Cambridge: Academic Press.
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997). Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Advanced Drug Delivery Reviews, 46(1-3), 3-26. https://doi.org/10.1016/s0169-409x(00)00129-0
Ma’arif, B., Mirza, D. M., Suryadinata, A., Muchlisin, M. A., & Agil, M. (2019). Metabolite Profiling of 96% Ethanol Extract from Marsilea crenata Presl. Leaves Using UPLC-QToF-MS/MS and Anti-Neuroinflammatory Predicition Activity with Molecular Docking. Journal of Tropical Pharmacy and Chemistry, 4(6), 261-270. https://doi.org/10.25026/jtpc.v4i6.213
Ma’arif, B. (2020). Aktivitas Antineuroinflamasi Ekstrak dan Fraksi Daun Semanggi (M. crenata Presl.) terhadap sel Mikroglia HMC3. Disertasi. Surabaya: Universitas Airlangga.
Ma'arif, B., Mirza, D. M., Hasanah, M., Laswati, H., & Agil, M. (2020a). Antineuroinflammation Activity Of N-Butanol Fraction of Marsilea crenata Presl. in Microglia HMC3 Cell Line. Journal of Basic and Clinical Physiology and Pharmacology, 30(6), 20190255. https://doi.org/10.1515/jbcpp-2019-0255
Ma'arif, B., Agil, M., & Laswati, H. (2020b). The Enhancement of Arg1 and Activated ERβ Expression in Microglia HMC3 by Induction of 96% Ethanol Extract of Marsilea crenata Presl. Leaves. Journal of Basic and Clinical Physiology and Pharmacology, 30(6), 20190284. https://doi.org/10.1515/jbcpp-2019-0284
Ma’arif, B., Muslikh, F. A., Fihuda, D. A. P., Syarifuddin, S., & Fauziyah, B. (2021a). Prediction of Compounds from 96% Ethanol Extract of Marsilea crenata Presl. Leaves in Increasing Estrogen Receptor-α Activation. Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR), 1, 67-76. https://doi.org/10.18860/planar.v1i0.1461
Ma'arif, B., Muslikh, F. A., Anggraini, W., Taek, M. M., Laswati, H., & Agil, M. (2021b). In vitro Anti-Neuroinflammatory Effect of Genistein (4', 5, 7-trihydroxyisoflavone) on Microglia HMC3 Cell Line, and In Silico Evaluation of its Interaction with Estrogen Receptor-β. International Journal of Applied Pharmaceutics, 13(4), 183-187. https://doi.org/10.22159/IJAP.2021.V13S4.43855
Ma'arif, B., Aminullah, M., Saidah, N. L., Muslikh, F. A., Rahmawati, A., Indrawijaya, Y. Y. A., et al. (2021). Prediction of antiosteoporosis Activity of Thirty-Nine Phytoestrogen Compounds in Estrogen Receptor-Dependent Manner Through In Silico Approach. Tropical Journal of Natural Product Research, 5(10), 1727-1734. http://dx.doi.org/10.26538/tjnpr/v5i10.6
Ma’arif, B., Muslikh, F. A., Najib, L. A., Atmaja, R. R. D., & Dianti, M. R. (2021d). In Silico Antiosteoporosis Activity of 96% Ethanol Extract of Chrysophyllum cainito L. Leaves. Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR), 1, 61-66. https://doi.org/10.18860/planar.v1i0.1460
Ma'arif, B., Fihuda, D. A. P., Muslikh, F. A., Syarifuddin, S., Fauziyah, B., Sari, D. P., et al. (2022a). Studi In Silico Penghambatan Aktivasi TLR2 Ekstrak Etanol Daun Semanggi (Marsilea crenata Presl.). Jurnal Tumbuhan Obat Indonesia, 15(1), 31-40. https://doi.org/10.22435/jtoi.v15i1.5792
Ma'arif, B., Muslikh, F. A., Amalia, D., Mahardiani, A., Muchlasi, L. A., Riwanti, P., et al. (2022b). Metabolite Profiling of the Environmental-Controlled Growth of Marsilea crenata Presl. and Its In Vitro and In Silico Antineuroinflammatory Properties. Borneo Journal of Pharmacy, 5(3):209-228. https://doi.org/10.33084/bjop.v5i3.3262
Ma’arif, B., Muslikh, F. A., Guhir, A. M., Fitri, H., Najib, L. A., Salmasfattah, N., et al. (2022d). Efek Penurunan Ekspresi MHCII Pada Sel Mikroglia HMC3 Teraktivasi M1 Polarity Oleh Fraksi n-Heksana dan Etil Asetat Daun Semanggi (Marsilea crenata Presl.). Journal Pharmasci (Journal of Pharmacy and Science), 7(1), 35-41. https://doi.org/10.53342/pharmasci.v7i1.271
Ma'arif, B., Suryanto, S., Muslikh, F. A., Suryadinata, A., & Fauziyah, B. (2022c). Systematic Review: Anti-Osteoporosis Potential Activities Of Phytoestrogen Compounds In Chrysophyllum cainito L., Elaeis guineensis Jacq., Lannea acida Rich., Marsilea crenata Presl., and Medicago sativa L. Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community), 19(1), 41-52. https://doi.org/10.24071/jpsc.003166
Ma'arif, B., Maimunah, S., Muslikh, F. A., Saidah, N. L., Fihuda, D. A., Khotimah, H., et al. (2022e). Efek Ekstrak Daun Marsilea crenata Presl. pada Aktivitas Lokomotor Ikan Zebra. FARMASIS: Jurnal Sains Farmasi, 3(1), 18-24. https://doi.org/10.36456/farmasis.v3i1.5389
Ma'arif, B., Muslikh, F. A., Fihuda, D. A. P., Khotimah, H., Taek, M. M., & Agil, M. (2022f). The Effect of Ethanol Extract of Marsilea crenata Presley Leaves on Rotenone-Induced Zebrafish Locomotor Activity. Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community), 19(2), 87-92. https://doi.org/10.24071/jpsc.004576
Makatita, F. A., Wardhani, R., & Nuraini. (2020). Riset In Silico dalam Pengembangan Sains di Bidang Pendidikan, Studi Kasus: Analisis Potensi Cendana Sebagai Agen Anti-Aging', Jurnal Sosial, Budaya dan Sains (ABDI), 2(1), 33–39.
Martin Y. C. (2005). A Bioavailability Score. Journal of Medicinal Chemistry, 48(9), 3164–3170. https://doi.org/10.1021/jm0492002
Mizuno, T. (2015) Neuron-Microglia Interaction in Neuroinflammation. Clinical and Experimental Neuroimmunology, 6(3), 225–231. https://doi.org/10.1111/cen3.12228
Muslikh, F. A., Samudra, R. R., Ma’arif, B., Ulhaq, Z. S., Hardjono, S., & Agil, M. (2022a). In Silico Molecular Docking and ADMET Analysis for Drug Development of Phytoestrogens Compound with Its Evaluation of Neurodegenerative Diseases. Borneo Journal of Pharmacy, 5(4):357-366. https://doi.org/10.33084/bjop.v5i4.3801
Muslikh, F. A., Samudra, R. R., & Ma'arif, B. (2023). Prediksi Senyawa Fraksi Etil Asetat Daun Semanggi (Marsilea crenata Presl.) Sebagai Agen Antineuroinflamasi (agonis ERα). JIKSN: Jurnal Ilmu Kesehatan dan Sains Nusantara, 1(1), 10-21.
Nurmianti, L. & Gusmarwani, S. R. (2020). Penentuan Lethal Dose 50% (LD50) Pestisida Nabati dari Campuran Buah Bintaro, Sereh, Bawang Putih, Lengkuas. Jurnal Inovasi Proses, 5(1), 22-26.
Nursamsiar, N., Mangande, M. M., Awaluddin, A., Nur, S., & Asnawi, A. (2020). In Silico Study of Aglycon Curculigoside A and Its Derivatives as α-Amilase Inhibitors. Indonesian Journal of Pharmaceutical Science and Technology, 7(1), 29-37. https://doi.org/10.24198/ijpst.v7i1.23062
Penn, D. J. (2002). Encyclopedia of Life Sciences: Major Histocompatibility Complex (MHC). London, UK: Macmillan Publishers Ltd.
Prieto-Martínez, F. D., Arciniega, M., & Medina-Franco, J. L. (2018). Acoplamiento Molecular: Avances Recientes y Retos. TIP Revista Especializada En Ciencias Químico-Biológicas, 21(Suppl 1), e20180143. https://doi.org/10.22201/fesz.23958723e.2018.0.143
Riwanti, P., Arifin, M. S., Muslikh, F. A., Amalia, D., Abada, I., Aditama, A. P., et al. (2021). Effect of Chrysophyllum cainito L. leaves on bone formation in vivo and in silico. Tropical Journal of Natural Product Research, 5(2):260-264. http://dx.doi.org/10.26538/tjnpr/v5i2.8
Sliwoski, G., Kothiwale, S., Meiler, J., & Lowe, E. W. Jr. (2014). Computational Methods in Drug Discovery. Pharmacological Reviews, 66(1), 334-395. https://doi.org/10.1124/pr.112.007336
Siswandono. (2015). Kimia Medisinal Jilid Satu (2nd edition). Surabaya: Universitas Airlangga.
Suhud, F. (2015). Uji Aktivitas In-silico Senyawa Baru 1-Benzil-3-benzoilurea Induk dan Tersubstitusi sebagai Agen Antiproliferatif. Jurnal Farmasi Indonesia, 7(4), 242-251.
Supandi, Yeni, & Merdekawati, F. (2018). In Silico Study of Pyrazolylaminoquinazoline Toxicity by Lazar, Protox and Admet Predictor. Journal of Applied Pharmaceutical Science, 8(9), 119-129. http://dx.doi.org/10.7324/JAPS.2018.8918
Syahputra, G., Ambarsari, L., & Sumaryada, T. (2014). Simulasi Docking Kurkumin Enol, Bismetoksikurkumin dan Analognya sebagai Inhibitor Enzim 12-Lipoksigenase. Jurnal Biofisika, 10(1), 55–67.
Syamsudin, T. (2015). Penyakit Parkinson. In: Syamsuddin, T., Subagya., & Akbar, M. (editor). Buku Panduan Tatalaksana Penyakit Parkinson dan Gangguan Gerak Lainnya. Kelompok Studi Movement Disorder. Jakarta: Perhimpunan Dokter Spesialis Saraf Indonesia. 9-31.
Villa, A., Vegeto, E., Poletti, A., & Maggi, A. (2016). Estrogens, Neuroinflammation, and Neurodegeneration. Endocrine Reviews, 37(4), 372–402. https://doi.org/10.1210/er.2016-1007
Yulianti, A. B., Sumarsono, S. H., Ridwan, A., & Yusuf, A. T. (2015). Hubungan Reactive Oxygen Species (Ros), Superoxide Dismutase (Sod) dengan Protein α-Sinuklein-Larut Air pada Batang Otak Tikus yang Diinduksi Rotenon. Global Medical and Health Communication, 3(2), 83-92. https://doi.org/10.29313/gmhc.v3i2.1508
Published
2022-12-05
How to Cite
MA’ARIF, Burhan et al. Antineuroinflammatory Properties of Compounds from Ethyl Acetate Fraction of Marsilea crenata C. Presl. Against Toll-Like Receptor 2 (3A7B) In Silico. Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR), [S.l.], v. 2, p. 8-20, dec. 2022. ISSN 2827-7848. Available at: <http://conferences.uin-malang.ac.id/index.php/planar/article/view/1831>. Date accessed: 18 apr. 2024. doi: https://doi.org/10.18860/planar.v2i0.1831.