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

Ni Made pitri Susanti1*, Ni Putu Linda Laksmiani1, I Made Agus Gelgel Wirasuta1, Ni Kadek Ayu Sandra Dewi1, Mitsue Oka1, Wayan Eka Heltyani1, I Gde Pande

Anindhita Putra Wicaksana1 1Department of Pharmacy, Faculty of Mathematics and Natural Sciences,

University of Udayana, Bukit Jimbaran, Badung, Indonesia, 80361 *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 4.0.1 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 -8.16 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

 

 

HMG-CoA REDUCTASEINHIBITOR ACTIVITY OF

ANTHOCYANIN FROM PURPLESWEET POTATO (Ipomoea

Batatas L.)by Ni Made Pitri Susanti

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HMG-CoA REDUCTASE INHIBITOR ACTIVITY OFANTHOCYANIN FROM PURPLE SWEET POTATO (IpomoeaBatatas L.)ORIGINALITY REPORT

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HMG CoA REDUCTASE INHIBITOR ACTIVITY OFANTHOCYANIN FROM PURPLE SWEET POTATO(Ipomoea Batatas L.)

NI MADE PITRI SUSANTI

Department of Pharmacy, Faculty of Mathematics andNatural Sciences, University of Udayana

2016

BACKGROUNDBACKGROUND

Hiperlipidemia

Increase in totalcholesterol, LDL,trigleserida or adecrease in HDL

HMG CoAReductase

Purple sweet statinsPurple sweetpotato (Ipomoea

batatas L.)anthocyanin

cyanidin

Peonidin acetylatedanthocyanins

anthocyanin

coronary heart disease, stroke, anticarcinogenic, anti inflammatory

Antihiperlipidemic?

In Silico (DockingMolekuler)

acetylated anthocyanins +HMG CoA Reductase

MATERIALMATERIAL

HMG CoA Reduktase 3D structure ( PDB with ID 2Q6C andnative ligand HR1)3D structure of acetylated anthocyaninsComputer with ArgusLab 4.0.1 and HyperChem 8 software

METHODSMETHODS

Docking MolecularMethod Validation

Optimization of AcetylatedAnthocyanin 3D Structure

D ki A t l t dDocking AcetylatedAnthocyanins to theHMG CoA Reductase

Enzyme

DataAnalysis

RESULT

• Comparison of layout of Copy Ligand (gray) with NativeLigand (yellow) to the protein HMG CoA Reductase.

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RESULT

Conformation RMSDBinding Energy(kcal/mol)

Hydrogen Bond

1 1.74 11.062 1.59 11.053 1 92 11 01

• Results of Native Ligand Docking with HMG CoA Reductase

692 LYS, 684SER, 590 ARG

3 1.92 11.014 1.77 11.015 4.85 8.996 4.79 8.487 4.95 8.428 4.99 8.349 4.99 8.1410 4.99 8.11

RESULT

• 3D Structure of Acetylated Anthocyanin after Single PointCalculation (a) dan Geometry Optimization Calculation (b)

a b

RESULT

a

b

• Interaction of Acetylated Anthocyanin and HMG CoAReduktase Enzyme

RESULT

Conformation Boinding Energy (kcal/mol) Hydrogen Bond

1 -8.162 -7.903 -7 64

Docking Result of Acetylated Anthocyanin to HMG CoA ReductaseEnzyme

1156 LYS, 684 SER, 590 ARG, 692 LYS, 981 GLY, 982 CYS

3 -7.644 -7.505 -7.486 -7.447 -7.438 -7.339 -7.27

10 -7.11

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 tothe enzyme HMG CoA Reductase, docking todrugs that act on the same receptor has beendone.

• Rosuvastatin• Binding energy : 8.93 kcal / mol.• Energy > native ligand lower bond stabilitythan the native ligand.

• Rosuvastatin : activity asantihiperlipidemia acylated anthocyanins (has alower stability than the native ligand) also haspotential as antihiperlipidemia

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CONCLUSION

• Acylated anthocyanins from purple sweetpotato has potential as HMG CoA Reductaseinhibitors in mechanism as antihiperlipidemiathrough hydrogen bonding at the 1156 LYS,SER 684 590 ARG LYS 692 981 and 982 GlySER 684, 590 ARG, LYS 692, 981 and 982 GlyCYS amino acids, with a binding energy of8.16 kcal/mol.

ACKNOWLEDGEMENT

This research was support by Ministry ofResearch, Technology and HigherEducation of the Republic of Indonesia

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