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Journal : Nexus Kedokteran Translasional

Pomegranate Extract Does Not Inhibit Sodium Glucose co-Transporter 2 Protein in Vero Cells Mila Ulfia; Dono Indarto; Amelya Augusthina Ayu Sari; Yuliana Heri Suselo
Nexus Kedokteran Translasional Vol 6, No 1 (2017): Nexus Kedokteran Translasional
Publisher : Fakultas Kedokteran Universitas Sebelas Maret Surakarta

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Abstract

Backgrounds: Mutation of SLC5A2 gene which encodes sodium glucose co-transporter2 (SGLT2) protein enhances glucose reabsorption on the kidney tubule in some patients with type 2 diabetes (DMT2). Dapagliflozine an oral antidiabetic drug, inhibits SGLT2 activity. Ellagic acid is able to inhibit SGLT2 protein in silico and highly found in pomegranate fruits. The aim of this study was to investigate the effect of pomegranate extracts on glucose levels in a model cell of African green monkey (Vero cell line). Methods: This study was an experimental laboratory with posttest only control group design. 1 x 106 Vero cells perwell were used in five experimental groups: negative control 1 (KKn1), KKn with 20% glucose (KKn2), positive control with dapagliflozine (KKp), ethanol and diethyl ether extract of pomegranate peel (KEDA), methanol extract of pomegranate seeds (BMA). Vero cells were then treated with 125 ppm pomegranate extracts (KEDA and BMA) and incubated for 24 hours. Cell morphology was observed under an inverted microscope with 100 x magnification. Glucose levels in Vero cells were measured using spectrophotometer. Collected data was analyzed descriptively. Result: Morphology of Vero cells was oval, soliter and centered nucleus and did not change during incubation with pomegranate extracts. Glucose levels in Vero cells treated with BMA (28.5 mg/dL) and KEDA (29 mg/dL) were higher than glucose levels in control groups KKp, KKn1, and KKn2 (2.5, 6.5 and 8 mg/dL respectively). Conclusion; Pomegranate extracts do not inhibit SGLT2 protein and increase glucose levels in Vero cells. Purification of pomegranate extracts is required for further investigation of the capability of ellagic acid inhibiting SGLT2 protein. Keywords: Ellagic acid, glucose level, pomegranate, SGLT2, type 2 diabetes.
Potency of Indonesian Herbal Compounds as Human Flavin Containing Monooxygenase 3 Inhibitor for Atherosclerosis Prevention Fadhila Balqis Nurfitria; RAJ Sri Wulandari; Dono Indarto
Nexus Kedokteran Translasional Vol 6, No 1 (2017): Nexus Kedokteran Translasional
Publisher : Fakultas Kedokteran Universitas Sebelas Maret Surakarta

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (14.209 KB)

Abstract

Introduction: Atherosclerosis complication in the cardiovascular system has been one of the biggest medical problems in recent years and the definitive treatment has not been found. Trimethylamine-N-oxide (TMAO) is a catalytic product of Flavin-Containing Monooxydase (FMO) 3 enzyme and might act as a predispostion factor for atherosclerosis. Indonesia has many herbal plants which can potentially be developed into antiatherosclerosis drug. This was an initial study of drug development which aimed to identify FMO3 inhibitors from Indonesian herbal plants by using molecular docking. Methods: It was a bioinformatics study which utilized all herbal compounds recorded in HerbalDB, had three dimentional structure, and met the criteria for Lipinski's rule of five. Methimazole was used as a standard ligand and hFMO model was determined using FMO protein template from Methylophaga aminisulfidivorans. Herbal compounds were molecularly docked with hFMO3 models using AutodockVina 1.1.2. PyMOL 1.7 dan Chimera 1.10rc were used for visualization of docking results. Binding affinity, binding site, and Lipinski's rule of five criterias were used to determine hFMO3 inhibitor candidates of herbal compounds. Results: Methimazole bound to the hFMO3 model at Asn194 with binding energy average of -3.8 kcal/mol. Droserone, vanillic acid, (s)-(+) abscisic acid, and sebacic acid had lower binding energy, had similar binding site, and had the best drug like property, compared with methimazole. Conclusion: Droserone, vanillic acid, (s)-(+) absicic acid, and sebacic acid become the potential candidates of hFMO3 inhibitor in silico. A future study using flexible ligand and flexible receptor docking methods is needed to get more accurate results. Keywords: Atherosclerosis, Molecular Docking, FMO3 inhibitor, Indonesian Herbal Plants
A Potential Candidate of Lactate Dehydrogenase Inhibitor Derived from Indonesia Herbal Compounds Adam Haviyan Nasrullah; Dono Indarto; Riza Novierta Pesik; R. AJ. Sri Wulandari
Nexus Kedokteran Translasional Vol 6, No 1 (2017): Nexus Kedokteran Translasional
Publisher : Fakultas Kedokteran Universitas Sebelas Maret Surakarta

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (14.209 KB)

Abstract

Introduction: Lactate dehydrogenase A (LDHA) is an enzyme that catalyzes pyruvate into lactate. LDHA plays an important role in promotion of cancer cells growth through increasing aerobic glycolysis. Because LDHA has a central role in energy metabolism, it become a molecular target for development of anticancer drug. This was a biocomputational study that aimed to identify Indonesian herbal compounds which became a potential candidate of LDHA inhibitor via molecular docking analysis. Methods: Samples in this study were Indonesian herbal compounds that met the following criteria: (1) Registered on Database Herbal Indonesia, (2) had three-dimensional structure, and (3) met the criteria Lipinski rule of five. Oxamate used as a ligand standard and was validated using Autodock Vina software. Herbal compounds were also docked using the same program. Docking results were visualized using PyMOL software. LDHA inhibitor candidate is determined by comparing herbal compounds and standard ligand in terms of binding energy, binding site and Lipinski criteria. Result: Oxamate interacting with LDHA had -4.26 0.06 kcal / mol binding energy and bound to six amino acid residues at Gln 99, Arg 105, Asn 137, Arg 168, His 192, and Thr 247. A lower binding energy was observed in 23 herbal compounds and these compounds bound to LDHA at least five amino acid residues like Oxamate. Herbal compounds Phaseolic Acid, Sebacic Acid, D (-) - Fructose, Suberic Acid and Pimelic Acid interacted with amino acid residues of LDHA as same as Oxamate. The other herbal compounds interacted with less or more than six amino acid residues of LDHA. Based on characteristics of five herbal compounds, Phaseolic Acid, Sebacic Acid and Suberic Acid were probably the best candidates of LDHA inhibitor. Conclusion: Phaseolic Acid, Sebacic Acid and Suberic Acid become biocomputationally the best LDHA inhibitor. Enzymatic assays are needed to investigate whether or not all these compounds can inhibit LDHA enzyme activity. Keywords : Cancer, Inhibitor LDHA, Molecular Docking, Herbal Indonesia