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Oxonantenine Derives from Annona reticulata is a Potential Candidate of DPP-4 Inhibitor for Diabetes Therapy PRATHITA NITYASEWAKA; DONO INDARTO; YULIANA HERI SUSELO
Nexus Biomedika Vol 5, No 2 (2016): Nexus Biomedika
Publisher : Nexus Biomedika

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Introduction: DPP-4 inhibitor is a new diabetic drug for patients with type 2 diabetes who do not achieve normal blood glucose levels using standard drugs such as metformin, sulfonylurea, meglitinide, thiazolidinedione, and ?-glucosidase inhibitor. Pharmacologically, DPP-4 inhibitor increases GLP-1 and GIP blood levels, leading to increase of insulin secretion. So far, Indonesian herbal plants have been used as an alternative therapy for diabetes but their active compounds have been unknown. The aim of this study was to identify phytochemicals derived from Indonesian herbal plants with DPP-4 inhibitor activity. Methods: This study was a bioinformatic study with a molecular docking method. Three-dimensional structure of DPP-4 was downloaded from Protein Data Bank with access code PDB 3F8S. Sitagliptin, a DPP-4 inhibitor, was used as a standard ligand and was obtained from ZINC database with access code ZINC22007143. HerbalDB and Pubchem databases were used to search three-dimensional structures of Indonesian phytochemicals. Before running molecular docking, all phytochemicals were selected using Lipinskis rule of five criteria. Molecular docking of these phytochemicals with DPP-4 was performed three times using Autodock Vina 1.1.2. Results of molecular docking were visualized using PyMol 1.7 and Chimera 1.9. Result: 422 Indonesian phytochemicals were docked with DPP-4. A lower binding affinity was observed in oxonantenine, compared with sitagliptin (-8.3 vs -8.5 kcal/mol respectively). In addition, oxonantenine has as same as binding sites with sitagliptin (Glu 205 and Glu 206). Oxonantenine interacts with DPP-4 at Tyr 547 as third residue, while third residue interaction of sitagliptin and DPP-4 was at Tyr 662. Oxonantenine was found in Annona reticulata. Conclusions: Oxonantenine which is an Indonesian phytochemicals may computationally become a candidate of DPP-4 inhibitor. In vitro study is needed to verify whether or not oxonantenine can inhibit DPP-4. Keywords: DPP-4, type 2 diabetes, molecular docking, oxonantenine.

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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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

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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

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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

PATH ANALYSIS ON THE EFFECTS OF BIO-PSYCHOSOCIAL FACTORS AND CALORIE INTAKE IN BLOOD GLUCOSE CONTROL IN PATIENTS WITH TYPE 2 DIABETES MELLITUS Isfaizah -; Bhisma Murti; Dono Indarto
PROSIDING SEMINAR NASIONAL & INTERNASIONAL 2017: PROSIDING IMPLEMENTASI PENELITIAN PADA PENGABDIAN MENUJU MASYARAKAT MANDIRI BERKEMAJUAN
Publisher : Universitas Muhammadiyah Semarang

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Background: Diabetes mellitus (DM) is a serious chronic disease with the tendency to deteriorate. The DM cases in worldwide in 2015 was 415 million people and it is estimated to increase as many as 642 million people affected in 2040. Indonesia ranked 7 in the world with 10 million cases of DM in 2015, about 90% of which were Type 2 Diabetes Mellitus. This study aimed to determine the effect of biopsychosocial factors and calorie intake on the blood glucose control in patients with Type 2 DM.Subjects and Method: This was an analytic and observational study with case control design. This study was carried out at Internal Medicine Polyclinic, Department of Endocrinology, Dr. Moewardi Hospital, Surakarta, Central Java, from October to November 2016. A total sample of 135 cases of Type 2 DM were selected for this study by fixed disease sampling. As many as 106 of these study subjects at HbA1c ?6.5% and 29 cases of Type 2 DM had HbA1c <6.5%. The dependent variable was HbA1c level. The independent variables were educational level, family income, psychological stress, calorie intake, and Body Mass Index (BMI). The data were collected by a set of questionnaire. HbA1c was measured by High Performance Liquid Chromatography (HPLC), which was recorded in the medical record. Calorie intake was measured by 24 hour food recall. Psychological stress was measured by International Physical Activity Questionnaire (IPAQ). The data was analyzed by path analysis on STATA 13.Results: Psychological stress (b=0.99, 95%CI=0.07 to 1.92, p=0.034), calorie intake (b= 1.84, 95%CI= -0.24 to 3.92, p=0.083), and BMI (b= 1.15, 95%CI= 0.22 to 2.08, p=0.016), had positive and statistically significant effect on HbA1c. Calorie intake increased BMI (b= 2.35, 95%CI=0.31 to 4.39, p=0.024), education decreased calorie intake (b=-2.26, 95%CI= -3.38 to -1.14, p<0.001), and family income increased calorie intake (b= 1.23, 95%CI= 0.26 to 2.21, p= 0.013). Conclusion: Calorie intake, BMI, psychologi stress, and s family income are associated with increase in HbA1c level. Education decreases HbA1c level via decreased calorie intake. Type 2 DM patients need to pay attention to these biopsychosocial factors and calorie intake in order to control blood sugar.Keywords: Biopsychosocial factors, calorie intake, HbA1c.

A case-control study related to vitamin and mineral intake in female adolescents with iron deficiency anemia Dwi Rahayu; Dono Indarto
Health Science Journal of Indonesia Vol 11 No 1 (2020)
Publisher : Sekretariat Badan Penelitian dan Pengembangan Kesehatan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22435/hsji.v11i1.3066

Latar belakang: Anemia defisensi besi (ADB) merupakan salah satu masalah nutrisi pada remaja putri di seluruh dunia. Penyerapan zat besi di usus halus dipengaruhi oleh adanya vitamin C, kalsium, dan zink pada makanan. Penelitian ini bertujuan untuk mengetahui hubungan pola konsumsi vitamin A, vitamin C, kalsium dan zink terhadap kejadian ADB pada remaja putri. Metode: Penelitian ini merupakan penelitian case control yang melibatkan 60 remaja putri dengan ADB dan 58 remaja putri tanpa ADB. Diagnosis ADB berdasarkan kadar Hb dan indeks eritrosit, dan semikuantitatif FFQ digunakan untuk menentukan asupan vitamin dan mineral. Semua data dianalisis menggunakan test chi square dan tes regresi logistik ganda dengan p<0.05. Hasil: Semua subjek penelitian mempunyai asupan vitamin A dan C harian yang cukup tetapi asupan kalsium dan zinknya tergolong kurang (dalam mg). Namun, mereka semua memiliki frekuensi harian yang berbeda dalam mengkonsumsi mikronutrien tersebut. Remaja putri dengan asupan vitamin A yang jarang (OR=2.67; CI95%=1.10-6.50; p=0.03) dan asupan kalsium yang sering (OR=2.27; CI95%=0.85-6.03; p=0.10) lebih berisiko terkena ADB dibandingkan dengan remaja putri dengan asupan vitamin A yang sering dan asupan kalsium yang jarang. Akan tetapi hanya asupan vitamin A yang memiliki efek signifikan secara statistik. Kesimpulan: Hasil penelitian ini menunjukkan bahwa tingginya risiko ADB pada remaja putri berkaitan dengan asupan vitamin A yang jarang. Kata kunci: anemia defisiensi besi, asupan mikronutrien, remaja putri Abstract Background: Iron deficiency anemia (IDA) is a nutritional problem that occurs in female adolescents around the world. Iron absorption in the small intestine is influenced by the presence of vitamin C, calcium, and zinc in ingested foods. This study aimed to investigate the relationship of vitamin A, vitamin C, calcium, and zinc intake with IDA in female adolescents. Methods: This case-control study was conducted in 60 anemic and 58 normal female adolescents. IDA diagnosis was determined using Hb levels and erythrocyte indexes and the semiquantitative food frequency questionnaire was used to determine vitamin and mineral intake. All collected data were analyzed using chisquare and multiple logistic regression tests with p<0.05. Results: All groups had an adequate intake of vitamin A and C but they had inadequate intake of calcium and zinc (in mg). However, they all had different frequencies in consuming those micronutrients. Rare intake of vitamin A (OR=2.67; CI95%=1.10-6.50; p=0.03) and frequent intake of calcium (OR=2.27; CI95%=0.85- 6.03; p=0.10) increased IDA, compared with frequent intake of vitamin A and rare intake of calcium but only vitamin A intake had a significant effect. Conclusion: Our findings suggest that a higher risk of IDA in female adolescents is related to a rare intake of vitamin A. Keywords: Iron deficiency anemia; micronutrient intake; female adolescents

Polimorfisme Gen Ferroportin (FPN1) Q248H dan Karakteristik Sosial Ekonomi Ibu Hamil dengan Anemia di Surakarta Nor Istiqomah; Vitria Sari Dewi; Arta Farmawati; Ahmad Hamim Sadewa; Yuliana Heri Soesilo; Kusumadewi Eka Damayanti; Dono Indarto
Pena Medika Jurnal Kesehatan Vol 4, No 1 (2013): PENA MEDIKA JURNAL KESEHATAN
Publisher : Universitas Pekalongan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.31941/pmjk.v4i1.284

Background: Iron deficiency anemia in pregnancy remains an important health problem in Indonesia. Ferroportin (FPN1) is one of important gene in iron metabolism encodes ferroportin for iron absorption, release, and recycle inside the body. The polymorphism of FPN1 Q248H alters negative charge of the amino acid sequence positively, hence influenced its ubiquitination and degradation. Beside of that, the high prevalence of anemia not only caused by genetics, nutrition, physiology of each pregant women, but also demographic factor and sosio-economic burden of family. This research will study the polymorphism of ferroportin Q248H and demographic character in pregnant women in Surakarta.Methods: The study using descriptive analytic case-control approach. The data used were from questionaire and blood sampling whose counted for screening anemia in private laboratorium. Pregnant women who had intention and had 10-25 week in pregnant were selected to be research subject. FPN1 Q248H polymorphism were determined using PCR-RFLP method. Analysis Chi-square dan Independent t-test used to conclude the relationship between each variable to anemic state of pregnant women in Surakarta. A p<0.05 was considered as significant. The study using decriptive analytic design method. Results: Prevalence of anemia in Surakarta is 25.7% with 80.7% have mild anemia. There was no varian in FPN1 Q248H. Majority of pregnant women in group of anaemia have demographic character like 20-25 old, multigravid, last education in High School, housewife, their income range from Rp 500.000,00 to Rp 1.000.000,00, and consume Fe tablet. The bivariat analysis show no statistical significancy of parity, maternal age, education, income, and comsumption of iron tablet to state of anaemia (p>0.05).Conclusions: The FPN1 Q248H polymorphism was not a risk factor for iron deficiency anemia in pregnant women, likewise socio-economic factors had no significant role to incidence of anemia in Surakarta. Keywords: Anemia in pregnancy, Ferroportin (FPN1) Q248H polymorphism, Socio-Economic

The effects of raja banana (Musa acuminata) peel extract on body weight, body mass index, body fat percentage, and visceral fat mass in male rats with obesity Kezia Elian Devina; Dono Indarto; Tri Nugraha Susilawati; Budiyanti Wiboworini
Jurnal Gizi dan Dietetik Indonesia (Indonesian Journal of Nutrition and Dietetics) VOLUME 12 ISSUE 2, 2024
Publisher : Alma Ata University Press

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21927/ijnd.2024.12(2).%p

Background: Obesity is a risk factor for metabolic syndrome which can increase mortality. Obese sufferers often fail to lose body weight (BW) through non-pharmacological therapy. Obesity synthetic drugs can cause side effects, so natural ingredients are needed as alternative therapies.Objectives: This study aims to determine the effect of raja banana peel extract (RBPE) on BW, body mass index (BMI), body fat percentage (BFP), and visceral fat mass in obese male rats.Methods: The research subjects were 30 male Wistar rats weighing 125-200 g, aged eight weeks. Obesity was induced by being given high-fat high fructose (HFHFr) feed for 28 days. Rats were randomized and divided into five groups: the negative control group (C-) was given standard feed and distilled water, the positive control (C+) was given standard feed and orlistat, treatment 1 (T1), treatment 2 (T2), and treatment 3 (T3). Which were given standard feed and RBPE doses of 200 mg/kgBW/day, 400 mg/kgBW/day, and 800 mg/kgBW/day. Data before and after the induction of obesity were analyzed using paired t-tests. BW, BMI, and visceral fat mass were analyzed using the One-Way Analysis of Variance (ANOVA) and Repeated Measure ANOVA tests. BFP was analyzed using the Kruskal-Wallis test and the Friedman test.Results: RBPE can significantly reduce BW (p=0.026), BMI (p<0.001), and BFP (p<0.001). However, all groups had no significant difference in visceral fat mass (p=0.187). T3 was the group with the lowest average BW, BMI, BFP, and visceral fat mass although the highest weight loss during the intervention period occurred in C+.Conclusions: RBPE has the potential as an alternative therapy for obesity because it can reduce BW, BMI, and BFP. Future studies can investigate the effect of RBPE on other obesity parameters such as lipid profiles.

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