HMG-CoA REDUCTASE INHIBITOR ACTIVITY OF ANTHOCYANIN FROM PURPLE SWEET POTATO (Ipomoea Batatas L.)

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1 HMG-CoA REDUCTASE INHIBITOR ACTIVITY OF ANTHOCYANIN FROM PURPLE SWEET POTATO (Ipomoea Batatas L.) Ni Made pitri Susanti 1*, Ni Putu Linda Laksmiani 1, I Made Agus Gelgel Wirasuta 1, Ni Kadek Ayu Sandra Dewi 1, Mitsue Oka 1, Wayan Eka Heltyani 1, I Gde Pande Anindhita Putra Wicaksana 1 1 Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Udayana, Bukit Jimbaran, Badung, Indonesia, *Corresponding author: dekpitsusanti@unud.ac.id Abstract Anthocyanins are compounds contained in the purple sweet potato (Ipomoea batatas L.), which in some other plants are known to be used as antihiperlidpidemia. Hyperlipidemia treatment is done by lowering total cholesterol, LDL, triglycerides and increase HDL. Decrease the amount of cholesterol in the body can be done by inhibiting the HMG-CoA reductase enzyme. This study was conducted to determine the activity of acylated anthocyanins in purple sweet potato as antihiperlipidemia through molecular docking. Molecular docking is an in silico method that uses software to determine the molecular activity of acylated anthocyanins as antihiperlipidemia against a target protein, the HMG-CoA reductase enzyme. Software used is ArgusLab and HyperChem 8. Data analysis was done by comparing the energy bond between acylated anthocyanins dan native ligand to the target protein. Molecular docking performed includes the preparation of 3D structures of proteins and anthocyanins, molecular docking method validation, optimization of the 3D structure and molecular docking to the HMG-CoA reductase enzyme with binding energy parameters. The lower the binding energy, the stronger and more stable the bond between the enzyme and anthocyanins. The results showed that anthocyanins form hydrogen bonds with the amino acid LYS1156, SER684, ARG590, LYS692, Gly981 and CYS982 of HMG-CoA reductase enzyme with a binding energy of kcal/mol. It can be concluded that anthocyanins have a potency as antihiperlipidemia through interaction with the enzyme HMG-CoA Reductase. Keywords: Anthocyanins, HMG-CoA reductase, antihiperlipidemia, Molecular docking

2 HMG-CoA REDUCTASE INHIBITOR ACTIVITY OF ANTHOCYANIN FROM PURPLE SWEET POTATO (Ipomoea Batatas L.) by Ni Made Pitri Susanti FILE ABST RAK-NI_MADE_PIT RI_SUSANT I.DOCX (13.14K) T IME SUBMIT T ED 29-DEC :13PM WORD COUNT 298 SUBMISSION ID CHARACT ER COUNT 1822

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4 HMG-CoA REDUCTASE INHIBITOR ACTIVITY OF ANTHOCYANIN FROM PURPLE SWEET POTATO (Ipomoea Batatas L.) ORIGINALITY REPORT %0 SIMILARIT Y INDEX %0 INT ERNET SOURCES %0 PUBLICAT IONS %0 ST UDENT PAPERS PRIMARY SOURCES EXCLUDE QUOT ES OFF EXCLUDE MAT CHES OFF EXCLUDE BIBLIOGRAPHY OFF

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9 12/30/2016 BACKGROUND HMG CoA REDUCTASE INHIBITOR ACTIVITY OF ANTHOCYANIN FROM PURPLE SWEET POTATO (Ipomoea Batatas L.) Hiperlipidemia Increase in total cholesterol, LDL, trigleserida or a decrease in HDL HMG CoA Reductase NI MADE PITRI SUSANTI anthocyanin Purple sweet potato (Ipomoea batatas L.) statins Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Udayana 2016 Peonidin cyanidin acetylated anthocyanins anthocyanin coronary heart disease, stroke, anti carcinogenic, anti inflammatory MATERIAL Antihiperlipidemic? In Silico (Docking Molekuler) HMG CoA Reduktase 3D structure ( PDB with ID 2Q6C and native ligand HR1) 3D structure of acetylated anthocyanins Computer with ArgusLab and HyperChem 8 software acetylated anthocyanins + HMG CoA Reductase METHODS RESULT Docking Molecular Method Validation Optimization of Acetylated Anthocyanin 3D Structure Data Analysis Docking Acetylated t Anthocyanins to the HMG CoA Reductase Enzyme Comparison of layout of Copy Ligand (gray) with Native Ligand (yellow) to the protein HMG CoA Reductase. 1

10 12/30/2016 RESULT Results of Native Ligand Docking with HMG CoA Reductase RESULT Conformation RMSD Binding Energy (kcal/mol) Hydrogen Bond 692 LYS, 684 SER, 590 ARG a 3D Structure of Acetylated Anthocyanin after Single Point Calculation (a) dan Geometry Optimization Calculation (b) b RESULT a RESULT Docking Result of Acetylated Anthocyanin to HMG CoA Reductase Enzyme Conformation Boinding Energy (kcal/mol) Hydrogen Bond b Interaction of Acetylated Anthocyanin and HMG CoA Reduktase Enzyme LYS, 684 SER, 590 ARG, 692 LYS, 981 GLY, 982 CYS Comparison of the Bindingd Energy of Acetylated Anthocyanin (Blue) and Native ligand on the HMG CoA Reductase Enzyme (Red) To compare the acylated anthocyanins affinity to the enzyme HMG CoA Reductase, docking to drugs that act on the same receptor has been done. Rosuvastatin Binding energy : 8.93 kcal / mol. Energy > native ligand lower bond stability than the native ligand. Rosuvastatin : activity as antihiperlipidemia acylated anthocyanins (has a lower stability than the native ligand) also has potential as antihiperlipidemia 2

11 12/30/2016 CONCLUSION Acylated anthocyanins from purple sweet potato has potential as HMG CoA Reductase inhibitors in mechanism as antihiperlipidemia through hydrogen bonding at the 1156 LYS, SER 684, 590 ARG, LYS 692, 981 and 982 Gly Gly CYS amino acids, with a binding energy of 8.16 kcal/mol. ACKNOWLEDGEMENT This research was support by Ministry of Research, Technology and Higher Education of the Republic of Indonesia REFERENCES Azam, F., A. M. Madi, H. I. Ali Molecular Docking and Prediction of Pharmakokinetic Properties of Dual Mechanisme Drugs that Block MAO B and Adenosine A 2A Receptor for the Treatment of Parkinson s Disease. Journal of Young Pharmacist. 4(3): Bullano, MF, Wertz DA, Yang GW, Kamat S, Borok GM, Gandhi S, McDonough KL, Willey VJ Effect of Rosuvastatin Compared with Other Statins on Lipid Levels and National Cholesterol Education Program Goal Attainment for Low Density Lipoprotein Cholesterol in a Usual Care Setting. Pharmacotherapy. 26(4): Dalimartha, S Atlas Tumbuhan Obat Indonesia Jilid IV. Puspa Swara. Jakarta. Koeswara S Teknologi Pengolahan Umbi umbian. Bagian 5: Pengolahan Ubi. Research and Community Service Institution. Agricultural Technology. Bogor. Mason, W.F., Christine, J Kolesterol t lrendah Jantung ShtA Sehat. Associate i t Professor The Medical School. PT Bhuana Ilmu Populer. Jakarta. Mayes, P.A, Botham, K.M Cholesterol Synthesis, Transport & Excretion. In : Murray,R.K, Granner,D.K, Mayes,P.A, Rodwell V.W. Editors. Harper s. Illustrated Biochemistry. Lange Medical Book. 26 th ed. New York. Montilla, Elyana Cuevas, S. Hillebrand, P. Winterhalter Anthocyanins in Purple Sweet Potato (Ipomoea batatas L.) Varieties. Fruit, Vegetable and Cereal Science and Biotechnology. Pidrayanti, L. T. M. U Artikel Penelitian Pengaruh Pemberian Ekstrak Daun Salam (Eugeniapolyantha) Terhadap Kadar LdL Kolesterol Serum Tikus Jantan Galur Wistar Hiperlipidemia. Fakultas Kedokteran Universitas Diponogoro. Semarang. Woolfe J.A Sweet Potato An Untapped Food Resource. Cambridge University Press. Cambridge. 3

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