Search

Type 2 diabetes mellitus triggers hypertension as a complication. The use of amlodipine and glibenclamide drugs simultaneously results in a synergistic and effective lowering of blood sugar and blood pressure. In the testing of bioavailability and bioequivalence, as well as the monitoring of drug concentrations in the blood, a sensitive bioanalytical approach that meets existing reference requirements, such as the European Medicines Agency (EMA) recommendation, is required. Presently, there is no simultaneous bioanalytical method of amlodipine and glibenclamide that meets EMA requirements. This study aimed to develop a sensitive bioanalytical method that fulfills EMA requirements for determining the levels of amlodipine and glibenclamide simultaneously. Amlodipine and glibenclamide in plasma were extracted with acetonitrile at 10°C. The derivatization was conducted using 0.08% 4-chloro-7-nitrobenzofurazan at pH 8.6 with Teorell and Stenhagen buffer for 20 min at 70°C, followed by the addition of 0.1 N sulfuric acid. High-performance liquid chromatography analysis used a LiChrospher RP 18 column with a size of 125×40 mm ID; mobile phase, acetonitrile: 0.01% phosphoric acid (52:48); flow rate of 1 mL/min; and emission and excitation wavelength for glibenclamide and amlodipine at 346 and 300 nm and 535 and 480 nm, respectively. The concentration ranges were 0.1-20 ng/mL for amlodipine and 1-200 ng/mL for glibenclamide. The average ranges of percentage coefficient of variation and percentage difference were 1.76%-14.62% and 4.48%-11.18% for amlodipine and 0.56%-11.92% and 2.92%-12.75% for glibenclamide. This sensitive and simultaneous bioanalytical method for amlodipine and glibenclamide fulfills the EMA requirements.

Molecularly imprinted mesoporous silica (MIPMS) is one of the methods to improve site accessibility molecule target on molecularly imprinted polymer (MIP) for application in solid-phase extraction (SPE). The MIPMS was prepared using salbutamol sulfate as template molecule, cetyltrimethylammonium bromide as a directing agent, and tetraethyl orthosilicate and methyltriethoxysilane were used as silica precursor and organosilane. In this study, two TEOS : MTES ratios were used. The MIPMS-2 with 3 : 1 ratio of TEOS : MTES has better analytical performance than the MIPMS-1 with 2 : 1 ratio of TEOS : MTES. The adsorption capacity of MIPMS-2 was about 0.0934 mg/g, and it was 0.0407 mg/g for NIPMS-2. The extraction ability of MIPMS-2 was good, with a recovery of about 104.79% ± 1.01% of salbutamol in spiked serum. The imprinting factor (IF) value obtained is 1.2. When serum was spiked with salbutamol and terbutaline, the ability of NIPMS-2 to recognize salbutamol increased. Therefore, optimizing the conditions for the MIPMS synthesis is necessary to produce a sorbent with better selectivity.

In Indonesia, plants have been indigenously used to treat various diseases and as cosmetics. It is always challenging to explore the molecular interactions of phenolic compounds towards the levels of constituents that contribute to the biological activities of plants. This study aimed to select a plant of the Zingiberaceae family with the highest phenolics and flavonoids, the strongest radical scavenging activity, and the best interaction towards tyrosinase in terms of docking score and binding mode. Initially, the total phenolics and radical scavenging capacity of Zingiberaceae plants, namely, Hedychium coronarium, Curcuma zedoaria, Curcuma heyneana, and Alpinia galanga, were determined using the Folin–Ciocâlteu method and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The main phytoconstituents of plants with the highest phenolic levels were docked to the binding site of tyrosinase. Three anti-melanogenesis agents commonly used in cosmetics, namely, arbutin, hydroquinone, and kojic acid, were used as the standard. Our study revealed that all the tested plants contain polyphenolic compounds in the range of 17.92 (C. zedoaria rhizome extract) to 252.36 (A. galanga rhizome extract) mg GAE/g and have radical scavenging capacity, with IC50 values in the range of 66.67 (A. galanga rhizome extract) to 320.0 (C. heyneana rhizome extract) μg/mL. A molecular docking simulation demonstrated that four constituents, i.e., kaempferol, galangin, ethyl p-methoxycinnamate, and 6-gingerol, could occupy the binding site of tyrosinase with prominent affinity and interact with essential residues of the enzyme. This study confirms that Alpinia galanga possesses the potential to be further developed as a cosmetic with a radical scavenging and tyrosinase inhibitory activity. However, it may be interesting to carry out further studies of how the plant extract affects the melanogenesis signaling pathway.

Abstract Objective The risk of contracting tuberculosis (TB) and the efficacy of TB therapy are affected by several factors, including genetic variation among populations. In the Indonesian population, data on the genes involved in drug transport and metabolism of TB therapy are limited. The aim of this study was to identify the genetic profile of the ABCB1 gene (rs1128503 and rs1045642) and CYP2E1 gene (rs3813867) in Indonesians with TB. This study was a cross-sectional study of 50 TB outpatients in Jambi city, Indonesia. Sociodemographic characteristics were obtained from medical records. Whole blood was collected, and genomic DNA was isolated. Single nucleotide polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism with HaeIII, MboI, and PstI for rs1128503, rs1045642 (ABCB1), and rs3813867 (CYP2E1), respectively. Result The frequency of alleles of each gene was analyzed by Hardy–Weinberg equilibrium. The genetic profiles of ABCB1 rs1128503 and rs1045642 were varied (CC, CT, TT), while CYP2E1 rs3813867 was present in CC (wild type). The genetic variations of ABCB1 and CYP2E1 may have no significant correlation with the duration of TB therapy. Nevertheless, this study may provide as preliminary results for the genetic profiles of ABCB1 (rs1128503, rs1045642) and CYP2E1 (rs3813867) in the Indonesia population.

Selenium (Se) is a trace mineral found in plants with a distinct sulfuric odor that is cardioprotective and reported to have low toxicity. West Java, Indonesia, has a variety of plants with a distinct odor that are consumed raw, such as jengkol (Archidendron pauciflorum). This study is conducted to determine the Se content of jengkol using the fluorometric method, where the jengkol extract is separated, and the Se content is detected using high-pressure liquid chromatography (HPLC), combined with fluorometry. Two fractions with the highest Se concentration (A and B) are found and characterized using liquid chromatography mass spectrometry to predict the organic Se content by comparing the results with those in the external literature. The Se content of fraction (A) is found to be selenomethionine (m/z 198), gamma glutamyl-methyl-selenocysteine-(GluMetSeCys; m/z 313), and the Se-sulfur (S) conjugate of cysteine-selenoglutathione (m/z 475). Furthermore, these compounds are docked on receptors involved in cardioprotection. The receptors are peroxisome proliferator-activated receptor-γ (PPAR-γ), nuclear factor kappa-B (NF-κB), and phosphoinositide 3-kinase (PI3K/AKT). The interaction of receptor and ligan that has the lowest binding energy of the docking simulation is measured with molecular dynamic simulation. MD is performed to observe bond stability and conformation based on root mean square deviation, root mean square fluctuation, radius gyration, and MM-PBSA parameters. The results of the MD simulation show that the stability of the complex organic Se compounds tested with the receptors is lower than that of the native ligand, while the binding energy is lower than that of the native ligand based on the MM-PSBA parameter. This indicates that the predicted organic Se in jengkol, i.e., gamma-GluMetSeCys to PPAR-γ, gamma-GluMetSeCys AKT/PI3K, and Se-S conjugate of cysteine-selenoglutathione to NF-κB, has the best interaction results and provides a cardioprotection effect, compared to the molecular interaction of the test ligands with the receptors.

Yuni Elsa Hadisaputri,1,2 Ummi Habibah,1,2 Fajar Fauzi Abdullah,2,3 Eli Halimah,1 Mutakin Mutakin,1 Sandra Megantara,1 Rizky Abdulah,1 Ajeng Diantini1 1Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, West Java, 45363, Indonesia; 2Central Laboratory, Universitas Padjadjaran, Jatinangor, West Java, 45363, Indonesia; 3Department of Chemistry, Faculty of Mathematic and Sciences, Universitas Padjadjaran, Jatinangor, West Java, 45363, IndonesiaCorrespondence: Ajeng DiantiniFaculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang KM.21, Jatinangor, West Java, 45363, IndonesiaTel +62-22-84288888 Ext. 3510Email diantini.ajeng@gmail.comIntroduction: Breast cancer is the second most common cancer in women globally, and the incidence rate has increased annually. Traditional medicine is frequently used as a cancer treatment, and soursop or Annona muricata L (A. muricata) is a traditional medicinal plant that has been widely used as an anticancer treatment and requires more thorough study.Methods: In this research, we prepared ethanol extract and three solvents, ie, ethyl acetate, n-hexane and water fractions of A. muricata leaves and assessed their antiproliferation and cytotoxic activity on MCF7 breast cancer cells compared with that on CV1 normal kidney cells; observation of cell morphology by stained with mixture of propidium iodide and 4ʹ,6-diamidino-2-phenylindole indicated that this treatment induced an ongoing process of apoptotic cell death in MCF7 cells. To clarify the cell death mechanism via apoptosis, we assessed the mRNA expression in the caspase cascade of caspase-9, caspase-3, and PARP-1, and anti-apoptotic, Bcl-2 which mediated cytotoxic activity of extracts and ethyl acetate fractions of A. muricata leaves against MCF7 cells.Results: The ethanol extract, ethyl acetate, n-hexane, and water fractions of A. muricata leaves had IC50 values of 5.3, 2.86, 3.08, and 48.31 μg/mL, respectively, in MCF7 cells but had no activity in CV1 cells. The high cytotoxic activity of A. muricata leaves was reflected by changes in the morphology of cancer cells that appeared after 6 h exposure to A. muricata leaf extract and ethyl acetate fraction; the membrane and nucleus of cells undergoing apoptosis were characterized by the rupture and loss of membranes and nuclei. The mechanism that mediates this cytotoxic activity in MCF7 cells was mediated through a decrease in the expression of Bcl-2 mRNA and an increase in caspase-9 and caspase-3 mRNA expression.Conclusion: Therefore, the leaves of the medicinal plant A. muricata contained compounds that on extraction exerted a highly effective activity as an anticancer treatment for breast cancer via induced apoptotic cell death.Keywords: soursop, Annona muricata L., MCF7 breast cancer cell, cytotoxicity, caspase-cascade

The rational preparation of molecularly imprinted polymers (MIPs) in order to have selective extraction of salmeterol xinafoate (SLX) from serum was studied. SLX is an acting β-adrenergic receptor agonist used in the treatment of asthma and has an athletic performance-enhancing effect. Molecular dynamics were used for the simulation of the SLX-imprinted pre-polymerization system, to determine the stability of the system. The computational simulation showed that SLX as a template, 4-hydroxyethyl methacrylate (HEMA) as a monomer, and trimethylolpropane trimethacrylate (TRIM) as a crosslinker in mol ratio of 1:6:20 had the strongest interaction in terms of the radial distribution functional. To validate the computational result, four polymers were synthesized using the precipitation polymerization method, and MIP with composition and ratio corresponding with the system with the strongest interaction as an MD simulation result showed the best performance, with a recovery of 96.59 ± 2.24% of SLX in spiked serum and 92.25 ± 1.12% when SLX was spiked with another analogue structure. Compared with the standard solid phase extraction sorbent C-18, which had a recovery of 79.11 ± 2.96%, the MIP showed better performance. The harmony between the simulation and experimental results illustrates that the molecular dynamic simulations had a significant role in the study and development of the MIPs for analysis of SLX in biological fluid.

Beta-blockers are antihypertensive drugs and can be abused by athletes in some sport competitions; it is therefore necessary to monitor beta-blocker levels in biological samples. In addition, beta-blocker levels in environmental samples need to be monitored to determine whether there are contaminants from the activities of the pharmaceutical industry. Several extraction methods have been developed to separate beta-blocker drugs in a sample, one of which is molecularly imprinted polymer solid-phase extraction (MIP-SPE). MIPs have some advantages, including good selectivity, high affinity, ease of synthesis, and low cost. This review provides an overview of the polymerization methods for synthesizing MIPs of beta-blocker groups. The methods that are still widely used to synthesize MIPs for beta-blockers are the bulk polymerization method and the precipitation polymerization method. MIPs for beta-blockers still need further development, especially since many types of beta-blockers have not been used as templates in the MIP synthesis process and modification of the MIP sorbent is required, to obtain high throughput analysis.

Soursop (Annona muricata Lin.) is a plant belonging to the Annonaceae family that has been widely used globally as a traditional medicine for many diseases. In this review, we discuss the traditional use, chemical content, and pharmacological activities of A.muricata. From 49 research articles that were obtained from 1981 to 2021, A.muricata’s activities were shown to include anticancer (25%), antiulcer (17%), antidiabetic (14%), antiprotozoal (10%), antidiarrhea (8%), antibacterial (8%), antiviral (8%), antihypertensive (6%), and wound healing (4%). Several biological activities and the general mechanisms underlying the effects of A.muricata have been tested both in vitro and in vivo. A.muricata contains chemicals such as acetogenins (annomuricins and annonacin), alkaloids (coreximine and reticuline), flavonoids (quercetin), and vitamins, which are predicted to be responsible for the biological activity of A.muricata.

BACKGROUND: Acetaminophen, when used at low doses is a safe drug, but at higher doses it induces apoptosis in hepatoma cells. Arcangelisia flava that grows widely in Kalimantan Island, Indonesia, contains berberine which is effective in protecting the liver. This work was aimed to study the effect of A. flava extract on the modulation of caspase-3 in acetaminophen-induced hepatotoxicity. METHODS: Thirty-five Wistar male rats were divided into groups: I the normal control (water); II the negative control (Arabic gum powder or PGA, 2% in suspension); III the positive control (silymarin); IV-VII (A. flava extract 100, 200, 400, and 800 mg/Kg of body weight (BW), respectively) for 14 days. At day 15th, group II-VII were induced with acetaminophen 1000 mg/Kg of BW per oral for 7 days along with the extracts. At day 22nd, the animals were measured for their serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and gamma-glutamyl transferase (GGT), histological examination, and Western blotting. RESULTS: Acetaminophen elevated the SGOT and SGPT (3x compared to normal group), and GGT (5x compared to normal group) of the animals in group II. Pre-treatment with higher doses of A. flava extract (group VI and VII) significantly prevented the biochemical changes induced by acetaminophen. Normal histology of the liver was showed by group I, III, VII, whereas dilated sinusoids, central vein (CV) lesion, and local haemorrage were observed in group II, IV, V and VI. Western blotting showed an inhibition of caspase-3 expression by A. flava extract in dose-dependent manner. CONCLUSION: A. Higher dose A. flava extract shows hepatoprotective activity by preventing the elevation of serum transaminases and transferase levels. Eventually, no damage in the acetaminophen-induced rat’s liver was observed. This plant modulates the expression of caspase 3 protein in dose-dependent manner. KEYWORDS: Arcangelisia sp, caspase-3, berberine, hepatoprotective activity, NSAIDs, yellow root

Studies have shown that about 65% of diabetics have hypertension. Treatment for diabetic patients with hypertension is usually given a combination of drugs such as amlodipine (AML) and glibenclamide (GLI). The aim of this study was to develop and validate the simple simultaneous analysis method for separation of AML and GLI using high-performance liquid chromatography (HPLC) with fluorescence detector without derivatization. The arrangement of isocratic and gradient methods, mobile phase compositions, and flow rates to develop and validate the simple simultaneous analysis method for separation of AML and GLI by nonderivatization HPLC fluorescence was done. Optimum condition was obtained using an RP 18 (125 mm × 4 mm, i.d., 5 μm) and guard column RP 18 (4 mm × 4 mm, i.d., 5 μm) with mobile phase composition containing acetonitrile and phosphate buffer pH 3.0 using a 20:80 gradient condition at flow rate 1.0 ml/min measured at 361 nm for λ excitation and 442 nm for λ emission for AML and 235 nm for λ excitation and 354 nm for λ emission for GLI. The analysis of AML and GLI demonstrated a valid result with r2 value 0.999, recoveries were 100.04% and 99.14% relative standard deviations were 0.508% and 0,797%, respectively, detection limits were 0.055 and 0.104 μg/ml, and quantification limits were 0.166 and 0.316 μg/ml, respectively. An accurate method of separation for AML and GLI using HPLC with fluorescence detector without derivatization has been validated.

Selenium is a trace element that provides protection against cellular damage and death. Previous research using several types of cells identified anti-oxidant, anti-inflammatory, and anti-apoptotic effects for selenium. One of the diseases related to selenium is cardiovascular disease, as low selenium intake has been linked to cardiomyopathy. However, the mechanism of the cardioprotective effects of selenium is not thoroughly understood. Several studies supported the possible effects of selenium on heart cell survival. In this review, we analyzed recent research (2015–2020) on the roles and mechanism of action of selenium in cell survival and its cardioprotective effects. Furthermore, the prevention of apoptosis through both intrinsic and extrinsic pathways is discussed in this review. Signalling pathways that regulate cell survival such as the p-AMPK, poly (ADP-ribose) polymerase-1, nuclear factor-erythroid 2-related factor-2, AKT/PI3K, and STAT pathways are involved in the protective effects of selenium. In addition, signaling pathways that affect heart cell survival include the AKT and STAT pathways. It also affects autophagy through the PPAR-γ pathway. These findings should facilitate further research on the cardioprotective effects of selenium.

Diazepam is a benzodiazepine that has the potency to be misused because it is effective, easily obtained, and inexpensive. The misuse of diazepam is to replace illegal drugs and be a sedative. Separation of diazepam is needed to detect possible drug abuse and to monitor drug levels in blood to ensure the effectiveness of the drug. This study was conducted to obtain a molecularly imprinted solid-phase extraction (MI-SPE) sorbent to separate diazepam from serum samples. This work started at the synthesis stage with the bulk polymerization method, using methyl methacrylate and acrylamide as functional monomers, diazepam as a template, and ethylene glycol dimethacrylate as a crosslinker. The polymer obtained was identified by its adsorption capacity and packaged into a solid-phase extraction (SPE) cartridge, and the extraction conditions were optimized. The optimization results were then used to extract diazepam from the serum sample. The test results showed that the adsorption ability of the molecularly imprinted polymer (MIP) with the functional monomer, methyl methacrylate, was 63.98 ± 0.1%, which is higher than that of the acrylamide MIP monomer, with a value of 43.27 ± 0.1%. The MIP sorbent of methyl methacrylate was applied to the SPE with 200 mg of polymer in a 3 mL cartridge. Diazepam added to serum samples were then passed through the MIP-SPE producing a percent recovery value of 95.31 ± 1.1% for MIP and 60.83 ± 0.3% for nonimprinted polymer (NIP). The results showed that the MI-SPE sorbent made from the monomer methyl methacrylate gave higher extraction recovery results than acrylamide, and it could be used for extracting diazepam from serum samples with or without other substances.

Objective: To analyze the role of selenium and glutathione peroxidase (GPx) in cervical cancer. Methods: Serum selenium concentrations and GPx activities of 19 women with cervical cancer along with their healthy counterparts (control group) were obtained. Selenium concentration were measured fluorometrically and GPx activities were measured spectrophotometrically based on the quantity of NADPH used in the reduction of glutathione. Results: The mean of serum selenium concentrations in cervical cancer group was significantly lower than that in the control group, 67.24±15 ng/mL and 77.05±12 ng/mL (p=0.03), respectively. The mean GPx activity in the cervical cancer group was also significantly lower than that in the control group, 128.18±38 ∆mmol NADPH/min/L and 148.9±23 ∆mmol NADPH/min/L (p=0.04), respectively. Multivariate analysis in the cervical cancer patients showed that the Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) staging score (early vs. advanced) was inversely correlated with serum selenium concentration (p=0.027). Conclusions: Serum selenium concentration and GPx activity was significantly lower in the cervical cancer patients. Our results demonstrate that selenium and GPx activity may have an important role in the carcinogenesis of cervical cancer.

Objective Probiotics are beneficial in human health. In this study, we investigated the effect of probiotics on absorption of amlodipine, a dihydropyridine calcium antagonist used in the treatment of angina and hypertension, in a rabbit model. Methods Lactobacillus plantarum IS-10506 probiotic was administered for 14 days to male New Zealand rabbits. Blood samples were collected before and after probiotic supplementation. Amlodipine (10 mg) was then administered to all groups. Blood samples from a marginal vein were withdrawn at 5, 15, 30, 60, and 120 minutes to determine amlodipine concentrations in rabbit plasma. Results Amlodipine concentrations in the L. plantarum IS-10506 group were 4.95 ± 1.22, 8.71 ± 0.69, and 12.48 ± 2.53 ng/ml, and those in the control group were 1.69 ± 0.31, 3.89 ± 1.23, and 7.17 ± 1.85 ng/ml at 30, 60, and 120 minutes, respectively after administration of amlodipine. Amlodipine concentrations in the L. plantarum IS-10506 group were significantly higher than those in the control group at 30, 60, and 120 minutes after amlodipine administration. Conclusion Our results suggested that supplementation of L. plantarum IS-10506 significantly increases amlodipine plasma concentrations in rabbits.

Molecularly imprinted polymer (MIP) computational design is expected to become a routine technique prior to synthesis to produce polymers with high affinity and selectivity towards target molecules. Furthermore, using these simulations reduces the cost of optimizing polymerization composition. There are several computational methods used in MIP fabrication and each requires a comprehensive study in order to select a process with results that are most similar to properties exhibited by polymers synthesized through laboratory experiments. Until now, no review has linked computational strategies with experimental results, which are needed to determine the method that is most appropriate for use in designing MIP with high molecular recognition. This review will present an update of the computational approaches started from 2016 until now on quantum mechanics, molecular mechanics and molecular dynamics that have been widely used. It will also discuss the linear correlation between computational results and the polymer performance tests through laboratory experiments to examine to what extent these methods can be relied upon to obtain polymers with high molecular recognition. Based on the literature search, density functional theory (DFT) with various hybrid functions and basis sets is most often used as a theoretical method to provide a shorter MIP manufacturing process as well as good analytical performance as recognition material.

Generally, regulation states that herbal medicines are remedies containing plants or preparation of plants as active ingredients only. Paracetamol is one of the drugs that is frequently added in herbal medicine to enhance the effect as an analgesic. The government regulation disallows chemical drugs contained in herbal medicine due to the toxic effect of uncontrolled consumption. On this study, the optical sensor membrane from polymer poly(methyl methacrylate) (PMMA) was synthesized by phase inversion method and was used to detect paracetamol in herbal medicine. PMMA was made in three different concentrations 5%, 7.5%, and 10% and was mixed with ferric chloride (FeCl3), Folin-Ciocalteu, and Nessler reagent as specific colorimetric reagents for paracetamol detection, with a ratio of solvent:reagent was 6:4; 7:3; and 8:2. The result of the experiment shows that PMMA-FeCl3 7.5% (7:3), PMMA-Folin 5% (6:4), and PMMA-Nessler 5% (6:4) give the best performance for paracetamol detection. Real herbal medicine samples were analyzed to confirm the practical application of this sensor, and the result shows good agreement with UV-Vis data. The results show that optical sensor membrane which has been developed can be used as new detection method of paracetamol for community application.

This research aims to analyze the judge's considerations in granting dispensation for child marriage in the Religious Courts Class I.B Blora (the case number 153/Pdt.P/2019/PA.Bla). This research is qualitative using a normative approach. Data were obtained through a review of several case examination documents, books, articles, journals, and regulations related to the research topic. According to the prevailing regulation, the age limit for marriage for both men and women is 19 years. If the man and woman have not reached the specified age, the family is allowed to apply for a marriage dispensation to the Court. This study found that the judge's considerations in deciding the case were based on the concept of sadd al-zari'ah (closing the path of evil). This is because in the case submitted there is two conflicting badness. First, the badness of early marriage relates to the health condition of the prospective bride and groom, which includes the health of reproductive organs, pregnancy, the expected child, and the possibility of a break in the household. Second, the bad impact that arises if the dispensation application was rejected, the two prospective brides continue to be involved in adultery. Of the two bad impacts, adultery is far worse. Based on the sadd al-dzarî'ah, the judge, therefore, granted the dispensation request.

Following a rigorous, carefully concerns and considered review of the article published in Jurnal Pendidikan Geografi to article entitle “Intensitas Konsumsi Pangan Lokal Sumber Karbohidrat Non Beras dalam Upaya Diversifikasi Pangan di Desa Hargorejo Kecamatan Kokap Kabupaten Kulon Progo” Vol 23, No 1 (2018), DOI: http://dx.doi.org/10.17977/um017v23i12018p009. This paper has been found to be in violation of the Jurnal Pendidikan Geografi publication principles and has been retracted. The article contained redundant material, the editor investigated and found that the paper published in Jurnal Geografi GEA, Vol. 17, No. 1 (2017), DOI: http://dx.doi.org/10.17509/gea.v17i1.5943. The document and its content has been removed from Jurnal Pendidikan Geografi, and reasonable effort should be made to remove all references to this article.