Dwi Aris Agung Nugrahaningsih
*) Department Of Pharmacology And Therapy, Faculty Of Medicine, Public Health And Nursing, Universitas Gadjah Mada; *) Herbal Medical Center, Faculty Of Medicine, Public Health, And Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

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The development of GAMA Swab sampling chamber for walk-through sampling in patients with COVID-19 at Gadjah Mada Hospital Hera Nirwati; Dwi Aris Agung Nugrahaningsih; Siswanto Siswanto; Mahatma Sotya Bawono; Titien Budhiaty; Setyawan Bekti Wibowo; Raden Sumiharto
Journal of Community Empowerment for Health Vol 3, No 2 (2020): Special Issue of COVID-19
Publisher : Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/jcoemph.57547

Abstract

Collecting swab samples from the nasopharynx and oropharynx of patients with COVID-19 is essential in detecting SARS-CoV-2. This procedure potentially produces sufficient droplets. Since SARS-CoV-2 is transmitted through droplets, swab sampling has to be done carefully to prevent the risk of transmission to healthcare workers or the cross-contamination to the environment. The GAMA Swab Sampling Chamber (GSSC) is a positive-pressure chamber designed for collecting swab samples involving the healthcare worker positioned inside, while the patient is outside the chamber. The chamber is designed to minimize the risk of aerosol exposure to the healthcare worker due to leakage or when opening or closing the door. Accordingly, the healthcare worker does not need to use complete personal protective equipment (PPE) as they do when collecting swab samples without the chamber. After several tests to check the safety and the chamber’s function, the GSSC was used at Gadjah Mada Hospital. This chamber had been used to swab 51 asymptomatic patients, 72 suspected patients, and 284 voluntary persons for ten weeks. The results of reverse transcription-polymerase chain reaction (RT-PCR) examination of all samples from asymptomatic patients were negative, while 2 of 72 suspected patients (2.8%) and 4 of 284 voluntary persons (1.4%) had positive RT-PCR results. The use of GSSC can simplify the swab sampling, also reduces the need for PPE usage and a negative pressure isolation room which are limited in the current pandemic situation.
Acute Oral Toxicity Test of Antihypertensive Polyherbal Preparations Containing Allium sativum Curcuma aeruginosa & Amomi fructus Herzan Marjawan; Woro Rukmi Pratiwi; Dwi Aris Agung Nugrahaningsih; Eti Nurwening Sholikhah; Pamungkas Bagus Satriyo
Majalah Farmaseutik Vol 18, No 4 (2022): in press
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/farmaseutik.v18i4.79299

Abstract

Hypertension is a major factor causing atherosclerotic cardiovascular disease, heart failure, stroke, and kidney failure. Polyherbal preparations containing garlic (Aliium sativum), temu ireng (Curcumae aeruginosae) and cardamom (Amomi fructus) have been widely used to treat hypertension. Despite widely used in community, its safety has not been evaluated. This study aimed to evaluate the single dose oral safety of the polyherbal. The acute oral toxicity test was done using fixed dose methods. Single dose of the polyherbal was administered to female Wistar rats. The clinical examination was done after administration of the polyherbal and continued until the 14th day to check for symptoms of toxicity, changes in body weight. On day 15, the animal was sacrificed and histopathological examination was conducted. The body weight did not differ between animal that received polyherbal and not received polyherbal. However, there was an increase in body weight in a group that received polyherbal at a dose of 2000 mg/kg. The absolute and relative organs weight was also similar among groups. There were no macroscopic and histopathological changes in kidney, liver, heart, spleen, aorta, and lungs. The polyherbal preparations containing Aliium sativum, Curcumae aeruginosae and Amomi fructus is safe with LD50 >2000-5000 mg/kg in Wistar rats.
Piper Crocatum Ruiz & Pav as A Commonly Used Typically Medicinal Plant From Indonesia: What Do We Actually Know About It? Scoping Review Andina Setyawati; Mae Sri Hartati Wahyuningsih; Dwi Aris Agung Nugrahaningsih; Christantie Effendy; Sam Ibeneme
Indonesian Contemporary Nursing Journal (ICON Journal) Vol. 7 No. 2 (2023): Volume 7 No. 2 Februari 2023
Publisher : Faculty of Nursing, Universitas Hasanuddin

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20956/icon.v7i2.23891

Abstract

Aims: Piper crocatum Ruiz & Pav (P. crocatum) has been widely used medicinally among ethnic communities in Indonesia to treat a variety of diseases through various preparationapplication techniques, duration, and frequency of use. Since research on the benefits of P. crocatum is still limited, our scoping review aimed to identify the key findings resulting from experimental studies regarding the medicinal uses of P. crocatum.Methods: We conducted a scoping review using the framework developed by Arksey and O?Malley. Databases were searched using CAB Direct, ProQuest, ScienceDirect, SpringerLink, and Google Scholar. Data were extracted and tabulated using Microsoft Office Excel 2013.Results: Sixteen articles fulfilled were included in the scoping review. Three key concepts were emerged from this scoping review: 1) Study characteristics indicated the most prevalent type of research was in vivo experiment (n=14) with the highest number of preparations using ethanol extracts (n=8) and P. crocatum sample were mostly sourced from Indonesia (n=9); 2) Seventeen screened metabolites were reported and the most frequently identified were steroids and flavonoids, followed by polyphenols and saponins; and 3) Eight potential activities of P. crocatum were reported as follows: anti-inflammatory, pro-wound healing, antibacterial, antioxidant, anti-necrotic, antitumoral, hepatoprotective, and anti-hyperglycaemic.Conclusion: P. crocatum has various metabolites that might influence the reported potential therapeutic activities with different preparation-application techniques, uses, and duration, yet the scientific evidence conducted in clinical study is still limited. Future research needs to perform testing standardized preparations of P. crocatum to be developed as novel therapeutic agents in wounds, infective diseases, cancers, diabetes, and liver diseases.
GSTM1 Deletion Compensated in mRNA Expression and 4T1 Viability After Editing Using CRISPR/Cas9 Single and Double gRNA Emilia Vivi Arsita; Dwi Aris Agung Nugrahaningsih; Ahmad Hamim Sadewa
The Indonesian Biomedical Journal Vol 15, No 2 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i2.2131

Abstract

BACKGROUND: Glutathione S-transferase Mu-1 (GSTM1) is known to undergo polymorphism and plays role in drug metabolism including Paclitaxel (PTX), the first-line chemotherapy for breast cancer. However, the effect of GSTM1 polymorphism against chemotherapy in breast cancer is limited and unexplored. This study was conducted to explore the effects of single and double guide (gRNA) on the GSTM1 knocked out (KO) and its effect on the response of PTX in the 4T1 cell line.METHODS: The preparatory stage was done by culturing and electroporating 4T1 cells using Ribonucleoprotein of clustered regularly interspaced short palindromic repeats (CRISPR)/Caspase 9 (Cas9). KO validation was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Sanger sequencing, and ICE analysis. The 4T1 viability was examined by MTT Assay.RESULTS: The number of base pairs of GSTM1 after being engineered by single or double gRNA was 86 bases. The DNA quantity of GSTM1 engineered by gRNA was more than using double gRNAs. The mRNA expression of GSTM1 engineered by single gRNA was lower than using double gRNAs. IC50 values of PTX between wildtype and KO were not significantly different, in the range of 30 µM.CONCLUSION: The base-pair length of GSTM1 exon 4 that is knocked out with single and double gRNA have the same number of base pairs. The quantity of GSTM1 DNA and mRNA expression are contrary between single gRNA and double gRNA, and IC50 PTX values in the 4T1 cell line of the control group with single or double gRNA knocked out do not differ markedly. PTX efficiency as chemotherapy is not disturbed in the GSTM1 deletion genetic profile.KEYWORDS: GSTM1, gRNA, Paclitaxel, CRISPR, breast cancer
Bioassay Guided Fractionation of Ciplukan (Physalis angulata L.) Monitored by Glucose Consumption Assay and Thin Layer Chromatography on Myoblast Cells Mae Sri Hartati Wahyuningsih; Ketut Shri Satya Wiwekananda; Aurelia Priscilla Regita Putri; Dwi Aris Agung Nugrahaningsih; Mia Munawaroh Yuniyanti
Majalah Obat Tradisional Vol 28, No 1 (2023)
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/mot.79783

Abstract

Ciplukan (Physalis angulata Linn.) has been used by the community as an anti-diabetic drug. The antidiabetic effect is due to ingredients such as unsaturated fatty acids, alkaloids, flavonoids, saponins, polyphenols, steroids, triterpenoids, monoterpenoids, and sesquiterpenoids. Part of the fruit of P. angulata contains many active substances of flavonoids with the proportion of fruit extract 300 μg/ml is 84%. Therefore the exploration for compounds responsible for antidiabetic activity in P. angulata needs to be done to ensure empirical evidence. The purpose of this study was to find the active fraction of P. angulata L. which has anti-hyperglycemic properties. This study used Myoblast cells as subjects and the Bioassay Guided Fractionation method for separating compound groups through three stages of the extraction, partitioning, and fractionation processes which were monitored using TLC and the Glucose Consumption Assay test. The results showed that the chloroform extract (CHCl3) was more active in lowering glucose levels compared to the methanol extract (MeOH) (4.86% vs -8.74%). MeOH insoluble extract was more active than MeOH soluble extract (5.14% vs -8.52). The fractionation results showed that Fraction I was the most active in lowering glucose levels compared to FII, III, and IV (26.47%; 13.18%; 0.15%; 13.76%). Therefore Fraction 1 which contains a class of flavonoid compounds is a potential candidate to be developed as an antidiabetic agent.
Bioanalytical Method Validation of Metformin Hydrochloride in Human Plasma by HPLC-UV for Preliminary Population-Based Pharmacokinetic Modeling Study Dimas Adhi Pradana; Erna Kristin; Akhmad Kharis Nugroho; Dwi Aris Agung Nugrahaningsih; Mustofa Mustofa; Ari Wibowo
Indonesian Journal of Chemistry Vol 23, No 4 (2023)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijc.77903

Abstract

This study aims to validate the method for measuring metformin hydrochloride plasma concentrations using High-Performance Liquid Chromatography (HPLC). This research performed chromatography on a 250 mm 4.6 mm 5 µm purosphere® Star RP-18 column at ambient temperature with a UV detector system at 233 nm. The mobile phase components were 70% phosphate buffer (KH2PO4) (10 mM), sodium dodecyl sulfate (0.3 mM), and 30% acetonitrile. It was pumped at an isocratic flow rate of 1.2 mL/min. Metformin HCl and ranitidine HCl (internal standard) were extracted using acetonitrile. The calibration curve was linear (R2 = 0.9998) in the 0.18–6 µg/mL concentration range. The lower limit of quantification (LLOQ) was 0.18 µg/mL. For intraday accuracy and precision, the percent difference and the coefficient of variation were less than 4 and 7%, and for inter-day were lower than 8 and 6%. The recovery average was 100.96%. The short-term plasma stability test was stable at 24 h at ambient temperature, and the long-term stability test was steady for 30 d at −20 °C. It was also stable after three freeze-thaw cycles. The method meets selectivity, sensitivity, linearity, accuracy, precision, recovery, carryover, and stability requirements and can be applied to population-based pharmacokinetic modeling.
2-(3-(chloromethyl)benzoyloxy)benzoic Acid Increases CD4+ Regulatory T-Cell Population and FoxP3 Expression in Lipopolysaccharide-induced Mice Yudy Tjahjono; Caroline Caroline; Jusak Nugraha; Kuncoro Foe; Srikanth Karnati; Süleyman Ergün; Nico Jafet; Oryza Chrisantia; I Made Andika Bara Kusuma; Hendy Wijaya; Wuryanto Hadinugroho; Dwi Aris Agung Nugrahaningsih; Dwi Liliek Kusindarta; Yufita Ratnasari Wilianto; Senny Yesery Esar; Hevi Wihadmadyatami
The Indonesian Biomedical Journal Vol 15, No 4 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i4.2429

Abstract

BACKGROUND: Lipopolysaccharide (LPS) has been reported to increase CD4+ regulatory T-cell (CD4+ Treg) populations. Acetylsalicylic acid (ASA) has been reported to have immunomodulatory activity, but it may induce chronic gastric ulceration. Another salicylic acid-bearing compound, 2-(3-(chloromethyl)benzoyloxy)benzoic acid (3-CH2Cl), has been reported to have less gastric mucosal damage. However, the effect of 3-CH2Cl on CD4+ Tregs in LPS-induced mice is still unknown. Therefore, the present study was conducted to investigate the immunomodulatory effect of 3-CH2Cl on CD4+ T-cell and CD4+ Treg populations as well as FoxP3 expression in LPS-induced mice.METHODS: Synthesis of 3-CH2Cl was performed by mixing salicylic acid and chloromethylbenzoylchloride with the catalyzation of pyridine, acetone and heat. The 3-CH2Cl tablets were prepared using direct compression method. After intraperitoneal injection of 1 mg/kg BW LPS to mice, 60 mg/kg BW ASA or 60 mg/kg BW 3-CH2Cl was given orally for 3 days. The splenocyte was obtained through splenectomy and collagenase digestion. The population of CD4+ T-cells and CD4+ Tregs, as well as the splenic FoxP3 expression were determined using flow cytometry technique.RESULTS: CD4+ T-cell populations in mice treated with LPS and 3-CH2Cl or ASA were lower than those treated with LPS merely. Meanwhile, CD4+ Treg populations and FoxP3 expression levels in mice treated with LPS and 3-CH2Cl or ASA were higher than those treated with LPS merely.CONCLUSION: Since 3-CH2Cl could decrease CD4+ T-cell population and increase CD4+ Treg population mediated by the increase of FoxP3 expression in LPS-induced inflammation, it may act as a potential therapeutic drug to reduce inflammatory conditions.KEYWORDS: 2-(3-(chloromethyl)benzoyloxy)benzoic acid, acetylsalicylic acid, CD4, T-regulatory cells, FoxP3, LPS
Fibrotic effect of monoculture, conditioned media and coculture of fibroblast NIH3T3 cells on collagen secretion and mRNA TGF-beta expressions Rizki Awaluddin; Dwi Aris Agung Nugrahaningsih; Prasetyastuti Prasetyastuti
Pharmaciana Vol 13, No 2 (2023): Pharmaciana
Publisher : Universitas Ahmad Dahlan

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.12928/pharmaciana.v13i2.25482

Abstract

Fibrosis is common profound in diabetes condition, they characterized by accumulation of extracellular matrix in tissue then cause tissue injury. The study aim to investigate effect of monoculture, conditioned media, and coculture of NIH3T3 cells in LPS-high glucose media conditions on mRNA TGF-B and collagen secretion. The fibroblast NIH3T3 were cultured with various culture type there is mono culture NIH3T3, conditioned media from RAW264.7 culture media, and coculture with RAW264.7 cells (ratio 1:1 and 1:2)  in normal media (media containing 4500 mikro g/mL of glucose) and HG-LPS media (media containing LPS 0.25 mikro g/mL and D-glucose 5400 mikro g/mL). Our study shows that mRNA TGF-B and collagen secretion of fibroblast NIH3T3 cells in monoculture and conditioned media from inflammatory macrophages are not statistically different. On other hand, the TGF-B mRNA expression and the relative ratio of collagen secretion in RAW 264.7 and NIH 3T3 cell coculture media with a culture ratio of 1:1 were the highest compared to other models (p kurang dari 0.05). Our study conclude that RAW 264.7 and NIH 3T3 coculture cells (1:1) in LPS and high glucose media is appropriate for fibrosis in vitro models.
The Genetic Polymorphisms of CYP3A4*1G and CYP3A5*3 in Javanese Indonesian Population: The Genetic Polymorphisms of CYP3A4*1G and CYP3A5*3 in Javanese Indonesian Atmaja, Sarah; Ellsya Angeline Rawar; Ani Kristiyani; Dwi Aris Agung Nugrahaningsih; Ahmad Hamim Sadewa; Christine Patramurti
Journal of Tropical Life Science Vol. 14 No. 1 (2024)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.11594/jtls.14.01.06

Abstract

Polymorphisms of CYP3A4*1G and CYP3A5*3 affect the pharmacokinetic profile of various drugs, e.g., fentanyl, tacrolimus, diltiazem, simvastatin. Tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR) is a simple and economical method for SNP determination. The polymorphisms in the CYP3A4*1G and CYP3A5*3 genes have not yet been examined using this method in Javanese Indonesian. Our aim was to determine the frequency of polymorphisms in the CYP3A4*1G and CYP3A5*3 genes in Indonesian Javanese using the ARMS-PCR method. Eighty-six patients at the Kalasan Community Health Centre in Yogyakarta, Indonesia, were chosen based on the inclusion criteria, which is Javanese ancestry. They gave their informed consent to blood collection by completing a form. Genetic variants were detected using Tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR). The chi-square test was used to determine genotype deviations from Hardy-Weinberg equilibrium, with a significant threshold of 0.05. For homozygous wild types, CYP3A4 *1/*1 dominated overall among study participants (73.35%), whereas for CYP3A5*3/*3, homozygous mutants were more prevalent (83.72%). Hardy-Weinberg equilibrium is consistent with genotype frequencies (p > 0.005). One participant carried a homozygous mutation for both CYP3A4*1G and CYP3A5*3, while the other 49 subjects were heterozygous for CYP3A4*1G and homozygous mutant for CYP3A5*3, which is the highest number of SNP combinations. The findings of the current investigation demonstrate that the population has the highest proportion of homozygous CYP3A4*1G wild-types (CYP3A4*1/*1) and homozygous mutants for CYP3A5*3 (CYP3A5*3/*3)
Development of nanocomplex mimic‐hsa‐miR‐143‐3p loaded exosome (exo‐miR) to inhibit viability, migration and proliferation of triple‐negative breast cancer Nilasari, Fita; Haryana, Sofia Mubarika; Nugrahaningsih, Dwi Aris Agung; Satriyo, Pamungkas Bagus
Indonesian Journal of Biotechnology Vol 29, No 4 (2024)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.92817

Abstract

Breast cancer represents the highest number of cancer cases in Indonesia, with triple‐negative breast cancer (TNBC) being a common subtype (10–15%). MicroRNAs play a role in cancer epigenetics and contributing as core factors to the disease. The expression of miR‐143‐3p have been found to be lower in breast cancer samples from Yogyakarta and Central Java. It is known that miR‐143‐3p functions as a tumor suppressor in breast cancer, and its overexpression corresponds with an increased survival rate. The structure of miRNA is quickly degraded, an enhanced delivery system for miRNA is required. Exosomes are indeed emerging as natural delivery agent. A new approach represents that exosomes will be transfected with mimic‐hsa‐miR‐143‐3p yield an exo‐miR. The research aimed to examine how exo‐miR affects viability, migration, and proliferation using 4T1 cell line. The Exo‐Fect‐based method was used to transfect mimic‐hsa‐miR‐143‐3p into exosomes. The MTT assay, wound healing assay, and colony formation assay were used as functional assay. The MTT assay revealed that 7.5 µL/ 250,000 particles exo‐miR obtained a lower percentage of cell viability (58%) than the control (99.7%). The wound healing assay showed that transfection of 37.5 µL/ 1,250,000 particles exo‐miR was able to suppress migration by the percentage of wound closure (67%) compared to the control (100%). Exo‐miR also had a significant (p < 0.001) effect on colony‐forming abilities, as shown by fewer colonies (32) compared to the control (132). This findings demonstrated that exo‐miR represents a promising targeted approach in cancer therapy.
Co-Authors Abdul Karim Zulkarnain Ade Saputri Aditya Nugraha Ahmad Hamim Sadewa Ajib Diptyanusa Akhmad Kharis Nugroho Amira Fawwaz Tsabitah Andina Setyawati Andrew Limavanady Ani Kristiyani Ari Wibowo Astika Widy Utomo, Astika Widy Atmaja, Sarah Aurelia Priscilla Regita Putri Budi Mulyaningsih Budi Mulyaningsih Buftheim, Sonia Caroline Caroline Christantie Effendy Christine Patramurti Denny Agustiningsih Dimas Adhi Pradana Dwi Liliek Kusindarta Eko Purnomo Ellsya Angeline Rawar Emilia Vivi Arsita Erna Kristin Ernaningsih Ernaningsih Eti Nurwening Sholikhah Eti Nurwening Sholikhah Foe, Kuncoro Gloria Evita Thalia Hendy Wijaya Hera Nirwati Herzan Marjawan Hevi Wihadmadyatami I Made Andika Bara Kusuma Ikhsan Nur Salim Ismawati, Yuyun Iwan Dwiprahasto Januar Rizqi Jonathan J Jumina Jusak Nugraha Katharina Oginawati Ketut Shri Satya Wiwekananda Mae Sri Hartati Wahyuningsih Mahatma Sotya Bawono Mia Munawarroh Yuniyanti Mosa Rini Nurul Hidayati Mubarika Haryana, Sofia Mustofa Mustofa Mustofa Mustofa Mustofa Mustofa Ngatidjan Ngatidjan Nico Jafet Nilasari, Fita Nur Arfian Oryza Chrisantia Pamungkas Bagus Satriyo Prasetyastuti Prasetyastuti Pratiwi, Woro Rukmi Probosuseno Probosuseno Raden Sumiharto Rahman, Intan Nur’azizah Rahmi Ayu Wijayaningsih Rahmi Ayu Wijayaningsih Rasya Mayora Ratna Sari Rizki Awaluddin Rocca, Matteo Ronny Martien Rul Afiyah Syarif Sam Ibeneme Satriyo, Pamungkas Bagus Senny Yesery Esar Setyawan Bekti Wibowo Setyo Purwono Siswanto Siswanto Sitti Rahmah Umniyati Sitti Rahmah Umniyati Sofia Mubarika Haryana Srikanth Karnati Süleyman Ergün Tety Hartatik Titien Budhiaty Tri Baskoro Tunggul Satoto Widya Wasityastuti Wuryanto Hadinugroho Yahiddin Selian Yasmeen Kwok Yudy Tjahjono Yufita Ratnasari Wilianto Yuliani, Fara Silvia Yuniyanti, Mia Munawaroh Zafrullah, Umar Farooq