Potensi Scopoletin sebagai Agonis Reseptor Transferin 2 untuk Pengembangan Terapi Anemia Defisiensi Besi

Asti Swari Paramanindita, Dono Indarto, Balgis Balgis


Introduction: Iron Deficiency Anemia (IDA) is caused by imbalance between iron intake and iron loss in blood circulation. Increased hepcidin level plays an important role in the etiology of IDA. Normally, expression of hepcidin protein is controlled by three different pathways, one of them is interaction between holo Transferin (Holo-Tf) and Transferrin Receptor 2 (TfR-2). Recently, Indonesian herbal plants have widely been used as herbal medicine but there is no active compound that can activate TfR-2 for IDA therapy. The aim of this study was to explore phytochemicals derived from Indonesian herbal plants to interact with TfR-2.

Methods: The study was a bioinformatics study with a molecular docking method. The SWISS-MODEL software was used to make TfR-2 protein modeling because the molecular structure of TfR-2 remains unknown. Holo-Tf was used as a standard ligand and obtained from Protein Data Bank with PDB ID 1SUV. All Indonesian phytochemicals which (1) registered at HerbalDB (2) had a three-dimensional molecular structure at PubChem (3) met Lipinski’s Rule of Five criteria were used in this study. AutoDock Vina 1.1.2 was used to analyze the binding affinity which was in kcal/mol. Phytochemical-TfR-2 binding complexes were visualized by using Chimera 1.10rc and or Pymol 1.7.

Result: The docking scores of holo-Tf modification with TfR-2 were -6,4±0,1 kcal/mol at Arg466 and -3,4±0,1 kcal/mol at Arg689 respectively. Interaction of modification holo-Tf and TfR-2 was observed not only at Arg466 and Arg689 but also with Asp642 and Ile682. Docking scores of scopoletin were -7,1±0,1 kcal/mol at Arg466 and -5,4±0,1 kcal/mol at Arg689. Scopoletin could interact with TfR-2 at Arg466, Arg689, and Leu630 residues.

Conclusions: Computationally, scopoletin is a potential TfR-2 agonist. In future studies, in vitro assay will be used to evaluate the agonist effect of scopoletin in TfR-2.



Keywords: Iron Deficiency Anemia, Phytochemical, Scopoletin, Molecular Docking, TfR-2

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Bregman DB, Morris D, Koch TA, He A, Goodnough LT. Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia. AJH 2013; 88(2): 97–101.

Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia i the 21st century. Therap Adv Gastroenterol 2011; 4(3): 177–184.

Pietrangelo A. Review Hepcidin in human iron disorders : Therapeutic implications. J Hepatol 2011; 54(1): 173–181.

Poli M, Asperti M, Ruzzenenti P, Regoni M, Arosio P. Hepcidin antagonists for potential treatments of disorders with hepcidin excess. Front Pharmacol 2014; 5: 1–13.

Fleming MD. The regulation of hepcidin and its effects on systemic and cellular iron metabolism. ASH 2008; 2008(1): 151–158.

Hernani. Pengembangan biofarmaka sebagai obat herbal untuk kesehatan. B Pascapanen 2011; 7(1): 20- 29.

Menkes RI 2013. Lampiran Peraturan Menteri Kesehatan Republik Indonesia Nomor 87 tahun 2013 tentang Peta Jalan Pengembangan Bahan Baku Obat. Jakarta: Menteri Kesehatan Republik Indonesia.

Yanuar A. Penambatan Molekular: Praktek dan Aplikasi pada Virtual Screening. Depok: Fakultas Farmasi Universitas Indonesia; 2012.

Lipinski CA, Lombardo F, Dorminy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 2001; 46(1-3): 3-26.

Yamamura T, Sakajiri T. The Computational Structure Model of The Differic Transferrin- Transferrin Receptor 2 Complex Involved in Body's Iron Homeostasis [Online]. 2011 [cited 2015 Aug 10]. Diunduh dari;URL:http://www2.kenes.com/apccn/scientific/Documents/Poster/1152.

Bordoli L. Introduction to 3D-Structure Visualization and Homology Modeling using the Swiss-Model Workspace [Online]. 2009 [cited 2015 Dec 3]. Diunduh dari; URL:http://edu.isb-sib.ch/pluginfile. php/735/course/section/1235/Introduction-SMW_partIV-ho.pdf.

Yuwono T. Biologi Molekular. Jakarta: Erlangga; 2008.

Hart DJ, Hadad CM, Craine LE, Hart H. Kimia Organik. Jakarta: Erlangga; 2003.

Merz KM, Ringe D, Reynolds CH. Drug design: Structure-and ligand-based approaches. New York: Cambridge University Press; 2010.

Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1(4): 337–341.

Hidayat T, Wahyuni ES, Karyono SS. Pengaruh ekstrak buah mengkudu (Morinda citrifolia) terhadap aorta terpisah marmut (Cavia porcellus) tanpa endotel. JKB [serial online] 2005 [cited 2015 Nov 25] Diunduh dari:URL:http://www.jkb.ub.ac.id/index.php/jkb/article/viewFile/244/234

Li C, Han X, Zhang H, Wu J, Li B. Effect of scopoletin on apoptosis and cell cycle arrest in human prostate cancer cells in vitro. Trop J Pharm Res 2015; 14(4): 611–617.

Malik A, Kushnoor A, Saini V, Singhal S, Kumar S, Yadav YC. In vitro antioxidant properties of Scopoletin. J Chem Pharm Res 2011; 3(3): 659–665.

Cheng AS, Cheng YH, Chang TL. Scopoletin attenuates allergy by inhibiting Th2 cytokines production in EL-4 T cells. Food Fuct 2012; 3(8): 886–890.

Pan R, Gao X, Lu D, Xu X, Xia Y, Dai Y. Prevention of FGF-2-induced angiogenesis by scopoletin, a coumarin compound isolated from Erycibe obtusifolia Benth, and its mechanism of action. Int Immunopharmacol 2011; 11(12): 2007–2016.


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