Prediction of Compounds from 96% Ethanol Extract of Marsilea crenata Presl. Leaves in Increasing Estrogen Receptor-α Activation
Abstract
Women who experience menopause will experience estrogen deficiency, which will impact their health, one of which will increase the risk of neurodegenerative. Phytoestrogen compounds in Marsilea crenata can provide activity after binding to their receptors or ER-dependent pathways. The research was conducted in silico with the molecular docking method using the ERα (1A52) receptor. In silico analysis was carried out on the metabolite profiling compound of the 96% ethanol extract of M. crenata leaves from the previous study. Sample preparation was carried out using the Biovia Discovery Studio 2021 application to separate macromolecules and native ligands and prepared to get a 3D structure using ChemDraw Ultra 12.0. then analyzed its pharmacokinetics and pharmacodynamics with the SwissADME webtool. Furthermore, the geometry of the compound was optimized using Avogadro 1.0.1, and molecular docking of the compound to the 1A52 receptor was carried out using Autodock vina (PyRx 0.8). The interaction visualization stage was carried out with Biovia Discovery Studio 2021, and a toxicity test was carried out using the ProTox II online tool. The results of the in-silico study showed that six compounds met the pharmacokinetic and pharmacodynamic criteria, toxicity, and had similar pharmacophore distances and amino acid binding with native 17β-estradiol, a 1A52 agonist with anti-neuroinflammatory effect. So, 96% ethanol extract of M. crenata leaves is predicted to potentially inhibit PD progression with an anti-neuroinflammatory mechanism.
References
Arwansyah, A. Ambarsari, L. Sumaryada, T. I. (2014) ‘Simulasi Docking Senyawa Kurkumin dan Analognya Sebagai Inhibitor Reseptor Androgen pada Kanker Prostat’, Current Biochem, Vol 1 (1): 11-19.
Balestrino, R. and Schapira, A. H. V. (2020) ‘Parkinson disease’, European Journal of Neurology, Vol 27.
Chagas, C. M. Moss, S. Alisaraiea, L. (2018) ‘Drug Metabolites and Their Effects on The Development of Adverse Reactions: Revisiting Lipinski’s Rule of Five’, International Journal of Pharmaceutics, Volume 549: pp.133– 149
Chen, W-W. Zhang, X. Huang, W-J. (2016) ‘Role of Neuroinflamation in Neurogenerative Disease’, Jiangsu: Molecular Medicine Report, Vol 13: 3391 – 3396.
Cherry, J. Olschowka, J. O’banion, K. (2014) ‘Neuroinflammation and M2 Microglia: The Good, The Bad, and The Inflamed’, J Neuroinflamm, Vol 11 (98)
Cui, J. Shen, Y. Li, R. (2013) ‘Estrogen Synthesis and Signaling Pathways durin Aggeing: From Periphery to Brain’, Trends Mol Med, 19(3)
Ekins, S. Mestres, J. Testa, B. (2007) ‘In silico Pharmacology for Drug Discovery: Applications to Targets and Beyond’, British Journal Pharmacology, Vol 152: 21-37
Kargozar, R. Azizi, H. Salari, R. (2017) ‘A Review of Effective Herbal Medicines in Controlling Menopausal Symptoms’, Electronic Physician, Vol 9(11): 5826-5833
Koeryaman, M. T. and Ermiati, E. (2018) ‘Adaptasi Gejala Perimenopause dan Pemenuhan Kebutuhan Seksual Wanita Usia 50-60 Tahun’, Medisains, Vol 16(1), 21.
Lipinski, F. L. Beryl W. D. Paul J. F. (1997) ‘Experimental and Computational Approaches to Estimate Solubility And Permeability in Drug Discovery and Development Settings’, Advanced Drug Delivery Reviews, Vol 23, Issues 1–3.
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. (2019) ‘Antineuroinflammation Activity of n-Butanol Fraction of Marsilea crenata Presl. in Microglia HMC3 Cell Line’, Journal of Basic and Clinical Physiology and Pharmacology, 20190255. 1-6.
Marotta, N. P. Lin, Y. H. Lewis, Y. E. Ambroso, M. R. Zaro, B. W. Roth, M. T. Arnold, D. B. Langen, R. Pratt, M. R. (2015) ‘O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease’, Nature chemistry, Vol 7(11)
Mirza, D. M. Ma’arif, B. Purbosari, I. Hardjono, S. Agil, M. (2021) ‘Prediksi Aktivitas Fitoestrogenik Senyawa Golongan Flavonoid terhadap Receptor Estrogen α (ER- α) dengan pendekatan In Silico’, Jurnal Sains dan Kesehatan, Vol 3(4)
Muchtaridi, M. Dermawan, D. Yusuf, M. (2018) ‘Molecular docking, 3D Structure-Based Pharmacophore Modeling, and ADME Prediction of Alpha Mangostin and Its Derivatives Against Estrogen Receptor Alpha’, Journal of Young Pharmacists, Vol 10(3)
Nurmianti, L and Gusmarwani, S. R. (2020) ‘Penentuan Lethal Dose 50% (LD50) Pestisida Nabati dari Campuran Buah Bintaro, Sereh, Bawang Putih, Lengkuas’, Jurnal Inovasi Proses, Vol 5(1)
Prabowo, S. A. A. and Santoso, B. (2018) ‘Profil In Silico Interaksi Senyawa Alam Ketumbar dan Adas Bintang sebagai Inhibitor Peptida Deformilase Mycobacterium Tuberculosis (3SVJ dan 1WS1) menggunakan Bantuan PyRx-Vina’, The 7th University Research Colloqium 2018, Surakarta : STIKES PKU Muhammadiyah.
Santoyo, A. H. Barajas, A. Y. T. Altuzar, V. (2013) ‘Protein-Protein and Protein-Ligand Docking’, In Tech, 64-81
Sliwoski, G. Kothiwale, S. Meiler, J. Lowe, E. W. (2014) ‘Computational Methods in Drug Discovery’, Pharmacol Rev, Vol 66(1): 334- 395
Suharna, S. (2012). Studi In Silico Senyawa Turunan Flavonoid Terhadap Penghambatan Enzim Tirosinase. Makassar: Program Sarjana UIN Alauddin.
Suharti. (2020) ‘Patofisiologi Penurunan Kognitif pada Penyakit Parkinson’, UMI Medical Journal, Vol.5: 1-11
Suhud, F. (2015) ‘Uji Aktivitas In-silico Senyawa Baru 1-Benzil-3-benzoilurea Induk dan Tersubstitusi sebagai Agen Antiproliferatif’, Jurnal Farmasi Indonesia, Vol 7(4)
Supandi, Y. and Merdekawati, F. (2018) ‘In Silico Study of Pyrazolylaminoquinazoline Toxicity by Lazar, Protox and Admet Predictor’, Journal of Applied Pharmaceutical Science, Vol 8(9)
Yang, T. S. Wang, S. Y. Yang, Y. C. Su, C. H. Lee, F. K. Chen, S. C. Tseng, C. Y. Jou, H. J. Huang, J. P. Huang, K. E. (2012) ‘Effects of Standardized Phytoestrogen on Taiwanese Menopausal Women’, Taiwanese Journal of Obstetrics and Gynecology, Vol 51(2): 229-235.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
