Indonesian Journal of Pharmacy <p>Thank you for visiting the Indonesian Journal of Pharmacy (ISSN-e: 2338-9486, ISSN-p: 2338-9427), formerly Majalah Farmasi Indonesia (ISSN: 0126-1037). The journal has been established in 1972, and online publication was begun in 2008. Since 2012, the journal has been published in English by Faculty of Pharmacy, Universitas Gadjah Mada (UGM), Yogyakarta, Indonesia, in collaboration with Ikatan Apoteker Indonesia (IAI) or the Indonesian Pharmacist Association and since then we only receive manuscripts in English. The Indonesian Journal of Pharmacy is accredited by the Directorate General of Higher Education (DGHE) DIKTI of Indonesia with no. 30/E/KPT/2018.</p> en-US (Prof. Dr. Abdul Rohman, M.Si., Apt.) (Puma Arfah) Wed, 29 Sep 2021 00:00:00 +0700 OJS 60 Narrative Review: Risk-Benefit Hydroxychloroquine and Chloroquine in COVID-19 <p>Chloroquine (CQ) and Hydroxychloroquine (HCQ) are highly prescribed as medications for COVID-19 infection, although no robust or convincing data has yet been published about the efficacy in COVID-19 patients. Therefore, risk and benefit assessment are necessary for decision to prescribe these drugs in COVID-19 patient in hospitals settings. We systematically searched from MEDLINE Database which investigate the benefits and risks of HCQ and CQ among COVID-19 patients. All records were searched using the search terms Hydroxychloroquine, Chloroquine, COVID-19, and SARS-CoV-2. The selection criteria include all clinical trials and observational studies. We found 11 records about benefit and 7 records about risks on HCQ and CQ in COVID-19 patients after following inclusion and exclusion criteria. From clinical trial and observational studies have showed that HCQ is very limited benefit particularly on reduction of mortality or clinical improvement. Similarly, there were seven observational studies have estimated the cardiac event in use of HCQ or CQ in COVID-19. Even though no increase death, but these studies reported the increase risk of prolong QT-interval in high proportion and other cardiac events such as arrythmia, torsade de pointes and conduction block. We conclude that the benefit effect of HCQ and CQ in COVID-19 remains very limited. However, both medications have independently shown to increase the risk in other populations for QT-interval prolongation, drug-induced torsades de pointes/TDP (a form of polymorphic ventricular tachycardia) and drug-induced other cardiac events.&nbsp;</p> Jarir At Thobari Copyright (c) 2021 Indonesian Journal of Pharmacy Tue, 10 Aug 2021 00:00:00 +0700 A Comprehensive Review on the Biomarkers of Bone Remodeling in Vitamin D Deficiency <p>Vitamin D (Vit.D) has been well regarded as one of the essential micronutrients for several biological functions in humans, including bone structure and function. The deficiency of Vit.D due to various environmental, lifestyle, and genetic factors affect bone remodeling, including bone mineralization and resorption. Consequently, several changes occur in the level of biochemicals which are implied in bone remodeling, either directly or via secondary pathways. Intriguingly, the levels of these biomolecules are hypothesized to have a strong association with the prognosis of Vit. D deficiency (VDD) related health complications. However, the precise association of various bone turnover-derived biomolecules with VDD-related effects are largely elusive. Thus, the in-depth understanding of specific associations of VDD and bone mineralization, would establish novel bioanalytical approaches for early detection and devise alternative strategies to provide symptomatic clinical support to VDD patients. Hence this review collates the available literature to elucidate the association of various bone resorption biomarkers and their relevance to VDD.</p> Arti Sureshkumar, Krishna Veni Nagappan Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 07:55:17 +0700 Natural Bioactive Cyclopeptides from Microbes as Promising Anticancer Drug Leads: A Mini-review <p>Natural products from microbes are a rich source of bioactive molecules to serve as drug leads, predominantly in cancer therapy. Peptides are among the essential nature-derived biomolecules. Owing to their great diversity and favorable characteristics, cyclic peptides (cyclopeptides) from natural sources have become a propitious lead candidate for the development of therapeutics, including anticancer drugs. This present mini-review highlights cyclopeptides from microbial-derived natural products that have demonstrated significant cytotoxicity or anticancer activities. Moreover, this mini-review also provides a look into the mode of action of anticancer cyclopeptides. Selected examples are given for the potent anticancer cyclopeptides isolated in the recent decade from fungi and bacteria from both terrestrial and marine origins. Naturally occurring cyclopeptides with canonical and non-canonical amino acids isolated from fungi, myxobacteria, actinomycetes, marine cyanobacteria, and microbes associated with marine organisms and their anticancer activity are featured herein.</p> Linda Sukmarini Copyright (c) 2021 Indonesian Journal of Pharmacy Tue, 10 Aug 2021 00:00:00 +0700 A Review on Chemical Composition, Bioactivity, and Toxicity of Myristica fragrans Houtt. Essential Oil <p><em>Myristica fragrans</em> Houtt., commonly known as nutmeg, is an Indonesian indigenous dioecious evergreen tree which contains 5-15% volatile oil. The oil is usually produced from the seed or mace.&nbsp; Nutmeg oil has been extensively utilized in aromatherapy, natural medicine, and the perfume industry. This article provides an overview of the chemical compounds, biological potency, and toxic effects of nutmeg essential oil compiled from recent literature (2000–2020). Nutmeg oil mainly comprises monoterpenes and phenylpropanoids. Several reports on gas chromatography-mass spectrophotometry analysis of nutmeg oil showed that there were 27–38 chemical constituents detected at various concentrations. Many secondary metabolites of nutmeg oil reported to show biological activities that possibly substantiate its utilization in natural medicine. Numerous studies reported the biological activities of this volatile oil such as antioxidant, analgesic, antiinflammation, anticonvulsant, antibacterial, antiparasitic, insecticidal, and anticancer activity. But large intake of nutmeg oil could cause intoxication which is shown through symptoms in cardiovascular, central nervous system, anticholinergic, and local effects in the stomach. These symptoms are mainly attributed to the effect of myristicin, safrole, and elemicin overdose. This updated review paper intends to attract more attention to nutmeg oil and its potential to be developed into a medicinal product for the prophylaxis and therapy of diseases.</p> Mega Ferdina Warsito Copyright (c) 2021 Indonesian Journal of Pharmacy Tue, 10 Aug 2021 00:00:00 +0700 Further Understanding about the Mechanism of Vitamin D on Blood Pressure <p>Globally, the prevalence of vitamin D deficiency and hypertension is both increasing. Various studies have also identified that both are likely to have causality relationships. The mechanisms and possibilities of such relationships will be discussed in this article. This literature study takes systematic review and meta-analysis research as well as randomly other research to complete the discussion on the role, effects, and mechanisms of vitamin D to blood pressure. Vitamin D is a fat-soluble vitamin that can be produced by the body and the most proper measurement using 25(OH)D. Low vitamin D is one of the risk factors for increased blood pressure (BP). Administration of vitamin D seems beneficial to lowering BP through various mechanisms including inhibit renin gene expression, maintain PTH levels and calcium homeostasis, vasodilatation BP, and decrease sympathetic nerve activity. Research with vitamin D supplementation reported random data between effective and whether or not to decrease BP. Vitamin D can be significantly beneficial in only some conditions although overall it has increased levels of 25(OH)D. However, although vitamin D is very good for health improvement, the use of vitamin D specifically as an antihypertensive still needs more understanding and research on the conditions that have proven effective in their use.</p> Farapti Farapti, Chusnul Fadilla Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 00:00:00 +0700 Potential Vaccine Targets for COVID-19 and Phylogenetic Analysis Based on the Nucleocapsid Phosphoprotein of Indonesian SARS-CoV-2 Isolates <p>Recently, the world is facing the outbreaks of severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 and the number of infected patients is increasing every day. Researchers are doing their best to find the most effective treatment to tackle this deathly virus. Several approaches had been proposed to be tested in the lab for the efficacy but none of them are qualified to be use as the treatment of the COVID-19. Therefore, the aim of this study is to design a vaccine based on epitope, which were obtained from the nucleocapsid phosphoprotein (N protein). In addition, 38 samples of SARS-CoV-2 Isolates were being retrieved from the GISAID Database and NCBI GenBank. Later on, these samples will be used for checking the evolutionary relationship of the SARS-CoV-2 and also, to determine whether this nucleocapsid proteins are well-conserved (less or even no mutations occur at all) and whether there was any evolutionary relationship between the recent coronavirus with the previous coronavirus by conducting the phylogenetic analysis. Then, we wanted to see the molecular interaction between the human BCR/FAB receptor with the predicted peptides through the molecular docking process. All of the peptides were generated by the IEDB analysis tools and have already been tested for the antigenicity, so the one that was being docked are the peptide that has antigen properties. Based on the analysis that had been done, we would like to recommend the PEP1 as an epitope-based peptide vaccine candidate to deal with the SARS-CoV-2 outbreaks.</p> Muhammad Aldino, Renadya Maulani, Rasyadan Probojati, Viol Dhea Karisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit Copyright (c) 2021 Indonesian Journal of Pharmacy Tue, 10 Aug 2021 00:00:00 +0700 Myrmecodia platytyrea Methanol Tuber Extract Ameliorates Hyperglycemia In STZ-Induced Diabetic Sprague-Dawley Male Rats <p>Type 2 diabetes mellitus (T2DM) is one of the main non-communicable chronic diseases that has many complications that compromise the quality of life. Hence, the need to find alternatives to replace the current therapy or as an adjuvant. Tubers of <em>Myrmecodia platytytrea</em> (Rubiaceae) has been used traditionally as an alternative therapy for the management of cancer and other inflammatory-related disorders. The aim of this study was to investigate the potency of <em>M. platytytrea</em> methanolic tuber extract (MPMTE) as an antihyperglycemic agent, <em>in vivo</em>. <strong>:</strong>The streptozotocin (STZ)-induced diabetic rats were treated orally with MPMTE (100, 200 and 400 mg/kg) and metformin (positive control, 100 mg/kg) daily for 14 days. Blood glucose level and other biochemistry analysis were conducted including histological examination on liver, kidney and pancreas. &nbsp;The STZ-induced diabetic rats treated with MPMTE (200 and 400 mg/kg) had significant decreased (<em>p</em>&lt;0.05) in fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein (LDL) with no significant changes in high-density lipoprotein (HDL) compared to STZ-induced untreated diabetic rats. Liver, kidney and pancreas were devoid of any damage caused by STZ. &nbsp;MPMTE had strong antihyperglycaemic activity and was protective against any STZ-induced organ damage. Thus, MPMTE can be further developed into an adjuvant therapy for diabetic patients.</p> Mizaton Hazizul Hasan, Hasbullani Zakaria, Ibtisam Abdul Wahab, Thellie Ponto, Aishah Adam Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 08:19:17 +0700 Population Pharmacokinetics Modeling of Levofloxacin In Rabbit By Intravenous Bolus Injection and Peroral Administration <p>The population-based approach has been widely applied to describe the pharmacokinetic profile of many drugs. The aim of this current research was to study the implementation of the population-based pharmacokinetics of levofloxacin in rabbits administered by intravenous bolus injection and peroral delivery.</p> <p>Modeling analyses were performed using Monolix, one of the alternative tools for the population-based approach. Monolix works based on the Stochastic Approximation Expectation-Maximization (SAEM) method. The analysis was performed based on the population model using one-compartmental and two-compartmental disposition models. The combination error model was used during the analyses. Modeling appropriateness was determined based on the goodness of fit analyses, i.e., 1) the individual fit, 2) the observed versus population prediction values; and 3) the observed versus individual prediction values</p> <p>Plasma concentration profiles of levofloxacin by intravenous bolus injection and oral administration are better described by an appropriate model using a two-compartmental disposition model. All goodness of fit analyses demonstrates the power of the chosen model. However, the estimated disposition parameter values obtained based on the intravenous bolus injection and peroral administration are different for each subject. To confirm this phenomenon, we performed a simultaneous fitting of all intravenous bolus as well as peroral administration data. The goodness of fit analyses indicates an adequate fitting of all data.</p> Akhmad Kharis Nugroho; Puspa Dwi Pratiwi, Shesanti Citrariana, Endang Lukitaningsih, Lukman Hakim Copyright (c) 2021 Indonesian Journal of Pharmacy Tue, 10 Aug 2021 00:00:00 +0700 LC-MS/MS and Cytotoxic Activity Analysis of Extract and Fraction of Calophyllum soulattri Stembark <p align="justify"><em>Calophyllum soulattri </em>(Sulatri), a plant from Clusiaceae family, has been empirically used as traditional medicine. In the present study, <em>C. soulattri</em> stem bark extract and fractions were evaluated for their toxicity against MCF-7 breast cancer cell. The extract and fraction’s chemical content was analyzed using the combination of liquid chromatography with mass spectrometry (LC-MS/MS). The results showed that methanol extract and n-hexane fractions have strong cytotoxic activity with IC<sub>50</sub> values 93.6 and 36 µg/mL, respectively. Meanwhile, as the positive control, ethyl acetate and cisplatin fractions have IC<sub>50</sub> values 233 and 16.2 µg/mL, respectively. The LC-MS/MS analysis showed that the extract and fractions contained polyporusterone A, poricoic acid D, polyporusterone F, esulentagenin, and 1-acetyl-3-(methoxy-carbonyl)-β-carboline. Therefore, <em>C. soulattri</em> stem bark extract and fractions have potential activity as an anticancer agent that was able to inhibit MCF-7 breast cancer cell growth.</p> <p><strong>&nbsp;</strong></p> Muhamad Salman Fareza, Nur Amalia Choironi, Sri Sutji Susilowati, Melina Puspita Rini, Vyola Festihawa, Irfansyah Septian Nur Fauzi, Esti Dyah Utami, Sarmoko Sarmoko Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 08:41:59 +0700 Anti-Aging Activity of Xylocarpus Granatum Phytoextracts and Xyloccensins K Compound <p align="justify">Cellular aging is promoted by the deleterious effect of free radicals. This can be lowered by antioxidant treatments. <em>Xylocarpus granatum </em>and its compound, Xyloccensins K have been reported to have antioxidant activity but there have been no reports of antioxidant and anti-aging activities at the cellular level. Thus, the aim of this study to investigate the antioxidant and anti-aging properties of <em>X. granatum</em>-derived extract and Xyloccensins K at a cellular level in yeast <em>Schizosaccharomyces pombe</em>. Four vegetative and three generative parts of <em>X. granatum </em>organs including root, stem, leaf, twig, seed, flesh of fruit, and peel of fruit were extracted using 70% ethanol by the maceration method. Whereas, Xyloccensins K was obtained from seed of <em>X. granatum</em>.&nbsp; The samples tested, other than peel of fruit, prolonged cell longevity in lower concentration as compared to that without phytoextracts treatment. Also, our data indicate that all samples could promote oxidative stress tolerance phenotype, as yeast was capable of dealing with H<sub>2</sub>O<sub>2</sub>-induced oxidative stress treatment at 1, 2, and 3 mM H<sub>2</sub>O<sub>2</sub> with the best phenotypes by the administration of twig extracts. Most of the phytoextracts showed an increase in mitochondrial activity, except that of seed extract<em>. </em>The result showed the administration of Xyloccensins K compound did not increase the expression of transcriptional factors of oxidative stress response gene cluster, <em>s</em><em>ty1 </em>and <em>p</em><em>ap1</em>. We suggest that the Xyloccensins K compound acts as direct Reactive Oxygen Species (ROS) scavenger. Thus further study in elucidating the phenomenon of longevity-induced <em>X. granatum </em>extract is required.</p> Syarif Maulana Yusuf, Rika Indri Astuti, Irmanida Batubara, Warinthorn Chavasiri Copyright (c) 2021 Indonesian Journal of Pharmacy Tue, 10 Aug 2021 00:00:00 +0700 Bioactivities of plant extracts collected in Halmahera, Indonesia: A bioprospection study of underexplored plant species <p>The discovery of new antibiotics to overcome the growing resistance problem as well as the discovery of new natural, safe antioxidants to combat oxidative stress are still urgently needed. Medicinal plants are known to produce potential therapeutic substances which are more biologically selective than synthetic compounds. Therefore, we explored the bioactivities of 35 ethanolic extracts from 24 underexplored plant species collected in Halmahera, to find potential sources for antibacterial and antioxidant agents.&nbsp;</p> <p>Dried plant parts were extracted using ethanol 96%. Thin layer chromatography-direct-bioautography (TLC-DB) and minimum inhibitory concentration (MIC) determination were used to evaluate the antibacterial effect. Antioxidant activity was determined against DPPH using TLC-DB and microdilution assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu’s method.</p> <p>The ethanolic extracts exhibited moderate to weak antibacterial activity against <em>Escherichia coli</em>&nbsp;and <em>Staphylococcus aureus</em>. However, the leaf extract of <em>Elaeocarpus dolichostylus, Elaeocarpus multiflorus, </em>and<em>&nbsp;Psychotria celebica </em>as well as the stem bark extract of<em>&nbsp;Elaeocarpus dolichostylus, Cinnamomum sintoc, </em>and<em>&nbsp;Garcinia latissima </em>displayed very strong antioxidant activities against DPPH with AAI values between 4.60 to 13.42<em>.</em>&nbsp;A strong correlation between TPC and antioxidant activity with r = 0.8712 was observed.</p> <p>Despite the moderate to weak antibacterial activity, eight underexplored plant species exhibit strong antioxidant activities. A high correlation between TPC and antioxidant activity indicating a prominent role of phenolic compounds in the plants’ antioxidant properties. These findings indicate that collected plants from Halmahera are potential to be studied and developed further as the potential sources for novel antioxidants.</p> Marlin Megalestin Raunsai, Kartika Dyah Palupi, Ahmad Fathoni, Andria Agusta Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 08:53:57 +0700 Formulation And Antioxidant Property Of Bitter Melon Seeds Oil Loaded Into SNEDDS Systems As A Nutraceutical <p style="margin: 0cm; text-align: justify;"><span lang="EN-US" style="font-family: 'Arial',sans-serif; color: #0e101a;">Bitter melon seeds oil is less soluble in the gastrointestinal tract and has low absorption. Therefore, a self-nanoemulsion dosage form needed to support its absorption and increase its stability. This study aimed to formulate bitter melon seeds oil into a self-nano emulsifying drug delivery system (SNEDDS) and evaluate its antioxidant activity using the Ferric Reducing Antioxidant Power (FRAP) method. The SNEDDS formulation uses bitter melon seed oil as the active ingredient and the oil phase, cremophor RH 40 as a surfactant, and glycerin as a co-surfactant. The results showed that the best SNEDDS formula obtains a ratio of oil: Smix (surfactant mixture) of 1:4. The best formula transmittance was 97.35 ± 0.04% with an emulsification time of 15.69 ± 0.06 seconds, a pH value of 6.87 ± 0.08, and a particle size of 31.8 ± 16.3 nm. Thermodynamic stability and robustness to dilution tests show the preparation is stable and resistant to various dilutions and pH. The antioxidant activity of bitter melon seed oil before and after being formulated into SNEDDS resulted in 62.73% and 50.31% reducing power. This result is not differences significantly. This study concluded that bitter melon seeds oil SNEDDS has good physical characteristics, stability, and no antioxidant activity changes.</span></p> Lina Winarti, Lusia Oktora Ruma Kumala Sari, Evi Umayah Ulfa, Dwi Ayu Samsuri Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 00:00:00 +0700 A Sesquiterpene Aldehyde Isolated From Ethyl Acetate Extract of Lansium Domesticum Fruit Peel <p align="justify"><em>Lansium domesticum</em> (fam. Meliaceae) contains various compounds with various biological activities. Based on the previous research, extracts from several parts of the plant have biological activity. This study aimed to isolate a compound from the fruitpeel of <em>L. domesticum</em> and evaluate cytotoxic activity against T47D, WiDr and HepG2 cell lines. Powdered peels were macerated with ethyl acetate and the filtrate was evaporated to give EtOAc extract. Dried extract was triturated with n-hexane to give n-hexane soluble fraction (A) and insoluble fraction (B). The fraction B was separated using vacuum column chromatography (VLC) with mobile phase n-hexane: ethyl acetate and given 5 fractions. Fractions B3-B5 were combined and separated using VLC with n-hexane and ethyl acetate as mobile phase. This VLC separation gave 18 subractions, subfractions 6-9 with the similar TLC profile were combined. This subfraction was separated further using preparative thin layer chromatography to give compound 1. The Isolated compound (1) appeared as liquid. The chemical structure of 1 was identified acoording to spectroscopic data and comparison with literature. Cytotoxic bioassay was performed on T-47D, WiDr and Hep G2 cell lines in a series of concentrations at 50, 40, 30, 20, 10 and 5µg/mL, with Doxorubicine used as positive control. According to spectroscopic data, compound 1 was identified as 2-ethyl,3-(1’-hydroxy-2’-menthene) propenal, and demonstrate the strongest cytotoxicity against T-47D cell lines (IC<sub>50</sub>=39.18+1.54 µg/mL).</p> Khusnul Fadhilah, Subagus Wahyuono, Puji Astuti Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 09:07:38 +0700 Β-Sitosterol of Red Dragon Fruit (Hylocereus Polyrhizus) and Its Response to Macrophage And Nitric Oxide <p align="justify"><em>Hylocerius polyrhizus </em>has relatively big potency as natural antioxidant. The compound considered as antioxidant also has immunomodulatory activity. This study showed isolation for identifying the active compounds in <em>H. polyrhizus </em>peels that are able to increase immune system of human body. The methanol extracts were partitioned and fractionated. The active compounds of petroleum ether fraction were partitioned and purified using Preparative Thin Layer Chromatography (PTLC). The identification of active compound structures was done with spectroscopy: UV, FT-IR, <sup>13</sup>CNMR, <sup>1</sup>HNMR, DEPT and HSQC. The immunomodulatory activity was also tested. Based on the spectroscopic data, the identified isolate was β-sitosterol. The statistical analysis of macrophage cell activity and nitric oxide showed that isolates at the highest concentrations of 100 µg/mL were able to activate macrophage cells and enhance the production of nitric oxide.</p> Sri wahdaningsih, Subagus Wahyuono, Sugeng Riyanto, Retno Murwanti Copyright (c) 2021 Indonesian Journal of Pharmacy Wed, 29 Sep 2021 09:14:43 +0700 Application of FTIR Spectroscopy Combined with Multivariate Calibrations for Analysis of Chloramphenicol and Hydrocortisone Acetate in Cream Samples <p align="justify">Analysis of chloramphenicol (CL) and hydrocortisone acetate (HCA) in cream samples using FTIR (Fourier Transform Infrared) spectroscopy. The objective of this study was to develop FTIR spectroscopy combined with multivariate calibrations for effective analysis of CL and HCA in cream formulation. High performance liquid chromatography (HPLC) method was applied for determining the actual value of CL and HCA. Cream samples containing CL and HCA were scanned using FTIR spectrophotometer employing attenuated total reflectance (ATR) technique. FTIR-ATR spectra were subjected to several optimization including wavenumbers selection and derivatization for quantitative analysis. The results showed that the optimum prediction model for correlation between actual values of CL and HCA as determined by HPLC and FTIR-predicted values was obtained using first derivative FTIR spectra at wavenumbers of 1500-1000 cm<sup>-1</sup>. The R<sup>2</sup> value for calibration and internal validation for CL and HCA was &gt; 0.9 with relatively small RMSEC (root mean square error of calibrations), RMSECV (root mean square error of cross validations) and PRESS (predicted residual error sum of squares) values. External validation of CL and HCA models produced R<sup>2</sup> &gt; 0.98 with RMSEP values of 0.6501 and 1.0041, respectively. The results of CL and HCA assay using HPLC and FTIR spectroscopy were compared resulting non-significant results (p &gt; 0.05) for these two methods. FTIR spectroscopy in combination with PLS can be used as a rapid and reliable analytical method for determination of CL and HCA in cream formulation.</p> Kusnul Khotimah, Sudibyo Martono, Anjar Windarsih, Irnawati Irnawati, Erna Prihandiwati, Abdul Rohman Copyright (c) Wed, 29 Sep 2021 00:00:00 +0700