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Abstrak :
Kanker serviks merupakan jenis kanker yang paling banyak dialami oleh wanita di Indonesia. Gangguan pada proses apoptosis merupakan tahapan yang penting dalam perkembangan tumor dan menyebabkan sel tumor lebih resisten terhadap terapi sitotoksik konvensional. Protein antiapoptosis Bcl-2 merupakan protein yang berperan penting dalam proses apoptosis yang bisa dijadikan molekul target obat antikanker. Asam galat merupakan senyawa penuntun yang telah terbukti secara in vitro memiliki aktivitas sebagai anti kanker. Penelitian ini bertujuan untuk mendesain, mensintesis dan menguji aktivitas sitotoksik turunan asam galat terhadap sel HeLa. Desain turunan asam galat dilakukan dengan metode structure based drug design untuk mendapatkan senyawa turunan yang menghambat protein anti apoptosis Bcl-2 dengan lebih baik. Lima senyawa turunan asam galat yang memberikan nilai ΔG terkecil dipilih untuk disintesis. Tiga senyawa turunan asam galat disintesis dengan reaksi kondensai dengan alkil halida, sedangkan dua turunan yang lain disintesis dengan reaksi esterifikasi menggunakan katalis DIC dan DMAP. Senyawa hasil sintesis diidentifikasi dengan menggunakan spektrofotometer FT-IR, Spektrometer massa, 1H-NMR dan 13C-NMR. Senyawa hasil sintesis dilakukan uji sitotoksisitas dengan metode MTT. Hasil pengujian sitotoksisitas menunjukkan bahwa tiga turunan ester asam galat memiliki aktivitas penghambatan yang lebih besar pada sel HeLa dibandingkan dengan asam galat dengan IC50 berkisar antara 30,20-34,43 μM. ...... Cervical cancer is the most common cancer among women in Indonesia. Impaired apoptosis is a central step in tumor development and renders the tumor cell more resistant to conventional cytotoxic therapy. Proteins Bcl-2, a protein that plays an important role in the process of apoptosis, could be used as an anticancer drugs target molecule. Gallic acid is a lead compound that has been proven have anticancer activity in vitro. The aims of this research are to design, synthesize, and evaluate the cytotoxic activity of gallic acid derivatives in HeLa cells. Gallic acid derivatives is designed by structure-based drug design as anti-apoptotic protein Bcl- 2. Five gallic acid derivatives with the smallest ΔG value are selected for synthesized. Three gallic acid derivatives synthesized by condensation reaction with an alkyl halide, while the other two derivatives were synthesized by esterification reaction using DIC and DMAP catalysts.The synthesized product identified by FT-IR, MS Spectrometer, 1H-NMR and 13C-NMR. Cytotoxicity evaluation are then done by MTT methode. It shows that three derivatives exhibited as a greater anticancer activity against HeLa Cell cells than the lead compound gallic acid with IC50 ranging of 30,20-34,43 μM.

Abstrak :
Bandotan Ageratum conyzoides L. merupakan salah satu tanaman herbal Indonesia yang banyak digunakan dalam pengobatan tradisional, salah satunya dalam terapi peradangan inflamasi. Penelitian sebelumnya mengungkapkan bahwa isolat kuersetin dari ekstrak daun bandotan memiliki aktivitas anti-inflamasi. Namun, dibutuhkan waktu yang lama dalam proses ekstraksi. Penelitian bertujuan mencari metode ekstraksi yang cocok yang dapat mempersingkat waktu ekstraksi dan meningkatkan kadar kuersetin dalam ekstrak, serta bertujuan menginvestigasi mekanisme molekuler anti-inflamasi dari ekstrak. Kuersetin, methotrexate dan piroxicam digunakan sebagai kontrol positif. Metode ekstraksi yang digunakan adalah maserasi dan digesti, dengan air dan etanol 70 sebagai pelarut. Profil metabolit sekunder dianalisis dengan kromatografi lapis tipis KLT dan Liquid Chromatography-Mass Spectroscopy LC-MS. Aktivitas anti inflamasi dari ekstrak dievaluasi dengan sel RAW 264.7 distimulasi oleh lipopolisakarida LPS dan dilakukan deteksi ekspresi gen-gen dengan Reverse Transcription-Polymerase Chain Reaction RT-PCR ditingkat messenger ribonucleic acid mRNA. Uji aktivitas juga dilakukan terhadap nitrit oksida NO dengan metode Griess. Hasil uji memperlihatkan bahwa kadar kuersetin tertinggi 52,71 ppm diperoleh dari metode digesti pada suhu 60 C selama 2 jam dengan pelarut etanol 70 . Kromatogram KLT menunjukkan pola yang khas dan kromatogram LC-MS memperlihatkan beberapa puncak metabolit sekunder, salah satunya adalah kuersetin. Pada dosis 50 ?g/ mL, ektrak dapat menurunkan ekspresi messenger ribonucleic acid mRNA cyclooxygenase-2 COX-2 , tumor necrosis factor-? TNF-? , interleukin-1betha IL-1? , IL-6, dan nuclear factor-kappa betha NF-?? , serta menurukan produksi NO. Berdasarkan hasil yang diperoleh, disimpulkan bahwa ekstrak etanol 70 daun bandotan memiliki mekanisme aksi anti-inflamasi seperti kuersetin dalam menekan mediator pro-inflamasi. ......Bandotan Ageratum conyzoides L. is one of Indonesian herbs are widely used in traditional medicines one of them is in treating inflammation. Previous research has revealed that the isolated quercetin from bandotan leaves extract has anti inflammatory activity. However, the extraction process takes a long time. The aim of the present study was to find the suitable method which can reduce the time of extraction process and also increase quercetin content in extract, and also investigates the anti inflammatory molecular mechanism of extract. Quercetin, methotrexate, and piroxicam were used as positive control. Two extraction methods were used maceration and digestion method, which used water and ethanol 70 as a solvent. Secondary metabolites profiles were analyzed by thin layer chromatography TLC and liquid chromatography mass spectroscopy LC MS . The anti inflammatory activity of extract was evaluated using RAW 264.7 cells stimulated by lipopolysaccharides LPS and the genes were detected by reverse transcription polymerase chain reaction RT PCR at messenger ribonucleic acid mRNA . The activity test was also performed on nitric oxide NO by Griess method. The results showed that the highest quercetin content 52.71 ppm was obtained from digestion method at 60 C for 2 hours with ethanol 70 as a solvent. TLC chromatograms shows a typical pattern and LC MS chromatograms shows some peaks of secondary metabolites, one of them is quercetin. The dose extract at 50 g mL can decrease mRNA expression of cyclooxygenase 2 COX 2 , tumor necrosis factor TNF , interleukin 1betha IL 1 , IL 6, dan nuclear factor kappa betha NF , and also can decrease of NO production. As a result, it is concluded that 70 ethanolic leaves extract of bandotan has anti inflammatory activity such as quercetin in suppressing pro inflammatory mediators.

Abstrak :
ABSTRAK
Pneumonia komunitas merupakan salah satu penyakit infeksi yang umum terjadi danmerupakan salah satu penyebab kematian dan kesakitan terbanyak. Penyakit ini memilikidampak terhadap sosioekonomi dimana tingginya biaya kesehatan terutama disebabkanoleh biaya rawat inap. Evaluasi farmakoekonomi dilaksanakan untuk menilai efektivitasbiaya antibiotik untuk mengetahui apakah pengobatan antibiotik memberikan outcometerapi yang baik dengan biaya yang minimal. Penelitian dilakukan terhadap kombinasiseftriakson-azitromisin dan levofloksasin tunggal sebagai antibiotik empiris untuk pasienpneumonia rawat inap. Analisis efektivitas biaya dilakukan dengan membandingkan totalbiaya medis langsung dan efektivitas yang dilihat dari lama rawat masing-masingkelompok pengobatan. Penelitian dilakukan di RSUP Persahabatan, Jakarta, dengandesain penelitian studi kohort retrospektif, dimana pengambilan data dilakukan secararetrospektif terhadap data sekunder, berupa rekam medis pasien dari tahun 2014-2016.Jumlah pasien yang dilibatkan dalam analisis 100 pasien, yaitu 64 pasien menggunakanantibiotik seftriakson iv dan azitromisin oral, dan 36 pasien menggunakan levofloksasiniv tunggal. Median biaya antibiotik berbeda signifikan antara kelompok seftriaksonazitromisindan kelompok levofloksasin, yaitu Rp.130.756,- dan Rp.286.952,-. Medianbiaya medis langsung kelompok seftriakson-azitromisin lebih tinggi dibandingkankelompok levofloksasin tunggal, yaitu Rp. 6.494.998,- dan Rp. 5.444.242,-. Keberhasilanterapi kelompok seftriakson-azitromisin yaitu 95,3 , sementara keberhasilan terapikelompok levofloksasin sebesar 97,2 namun tidak terdapat perbedaaan signifikan.Median lama rawat LOS dan lama rawat terkait antibiotik LOSAR kelompoklevofloksasin berturut-turut sebesar 6 hari dan 5 hari, lebih singkat dibandingkan LOSdan LOSAR kelompok seftriakson-azitromisin, yaitu 7 hari dan 6 hari. Nilai ACERkelompok levofloksasin sebesar Rp.56.011,-/persen efektivitas lebih rendahdibandingkan kelompok seftriakson-azitromisin sebesar Rp. 68.153,-/persen efektivitas.Berdasarkan hasil penelitian disimpulkan bahwa levofloksasin lebih cost-effectivedibanding kombinasi seftriakson-azitromisin.

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ABSTRACT
Community Acquired Pneumonia CAP is one of the most common infectious diseasesand is one of the leading causes of death and morbidity. This disease has an impact onsocioeconomic where the high cost of health is mainly caused by the cost ofhospitalization. A pharmacoeconomic evaluation was conducted to assess the costeffectivenessof antibiotics to find out whether antibiotic treatment results in a goodtherapeutic outcome with a minimal cost. The study was conducted on a combination ofceftriaxone azithromycin and single levofloxacin as an empirical antibiotic for inpatientCAP patients. Cost effectiveness analysis is conducted by comparing the total directmedical costs and the effectiveness measured from length of stay of each treatmentgroup. The study was conducted in RSUP Persahabatan, Jakarta, with a cohortretrospective design study, where retrospective data retrieval was conducted onsecondary data, in the form of patient medical records from 2014 2016. The number ofpatients involved in the analysis of 100 patients, ie 64 patients using combination of ivceftriaxone and oral azithromycin, and 36 patients using single iv levofloxacin. Medianantibiotic costs differed significantly between the ceftriaxone azithromycin group andthe levofloxacin group, which were Rp.130,756, and Rp.286,952, . Median directmedical costs of the ceftriaxone azithromycin group were higher than the singlelevofloxacin group, which was Rp. 6,494,998, and Rp. 5,444,242, . Success rate ofgroup of ceftriaxone azithromycin group was 95.3 , while the success rate oflevofloxacin group was 97.2 but there was no significant difference. Median length ofstay LOS and length of stay antibiotic related LOSAR of levofloxacin group wererespectively 6 days and 5 days, shorter than LOS and LOSAR of ceftriaxoneazithromycingroup, which were 7 days and 6 days. The value of the ACER levofloxacingroup was Rp.56.011, percent effectiveness, lower than the ceftriaxone azithromycingroup of Rp. 68.153, percent effectiveness. Based on the results of the study, it isconcluded that levofloxacin is more cost effective than a combination of ceftriaxoneazithromycin.

Abstrak :
Surgical site infections are the second most frequent nosocomial infection after catheter infection. They are associated with increase morbidity and mortality, iength of stay in hospital and cost of care. Antibiotic prophylaxis use is addressed to reduce incidence of surgical site infection. The aim of this research was to find out the pattern of antibiotic prophylaxis use; incidence of surgical site infection; association between antibiotic prophylaxis use and incidence of surgical site infection; and other factors that influence the incidence of surgical site infection. This research was carried out in Dr. Cipto Mangunkusumo Hospital Jakarta and it was a retrospective study with cross-sectional design. A total of 220 samples had been taken proportional randomly according to the type of surgery division from 1,841 medical records in 2005. The result showed that the most antibiotic prophylaxis frequently used was cephalosporin (first and third generation). followed by phosphomycin and metronidazole. Most of the patients were given antibiotic prophylaxis in inappropriate time and the duration of use was more than one day. This study found that the incidence of surgical site infection was 8.6% with the highest percentage occurred at orthopedic surgery (23.3%). Statistically, there was no relationship of class. Timing and duration of antibiotic prophylaxis use with incidence of surgical site infection. Adherence of antibiotic prophylaxis use to hospital guideline was not influenced the incidence of surgical site infection. Multivariate analysis with logistic regression analysis showed that the incidence of surgical site infection were influenced by the type of surgery (OR=2.6) and the use of antibiotics during hospitalization prior to surgery (OR=3.2). The conclusion of this research were the incidence of surgical site infection relatively high and class. timing, duration and adherence to hospital guideline of antibiotic prophylaxis use did not influence it. The wound contaminated and the use antibiotics during hospitalization prior to surgery were risk factors for surgical site infection. It was recommended that the hospital management revise the currently used surgical antibiotic prophylaxis guideline which is no longer relevant to the current situation.

Abstrak :
Penggunaan antibiotika yang tidak tepat dapat menimbulkan berbagai masalah kesehatan dan keamanan pasien. Upaya untuk memaksimalkan penggunaan antibiotika yang rasional merupakan salah satu tanggung jawab apoteker. Penelitian ini bertujuan untuk mengevaluasi kualitas penggunaan antibiotika di ruang kelas 3 infeksi Departemen Ilmu Kesehatan Anak (IKA) RSCM dengan metode Gyssens dan mengevaluasi pengaruh intervensi apoteker dalam meningkatkan kualitas penggunaan antibiotika dan outcome terapi. Penelitian dilakukan secara prospektif selama periode Januari ? April 2011 dengan pendekatan deskriptif-korelatif. Rekomendasi diberikan kepada penulis resep terhadap masalah ketidaktepatan penggunaan antibiotika yang ditemukan. Penggunaan antibiotika di ruang Kelas 3 infeksi sebesar 78,82% dari 170 pasien. Evaluasi kualitatif dengan metode Gyssens mendapatkan bahwa penggunaan antibiotika yang rasional sebesar 60,4% sedangkan yang tidak rasional sebesar 39,6%. Lama rawat, asal ruangan pasien, jumlah obat dan jumlah antibiotika yang digunakan pasien berpengaruh terhadap kualitas penggunaan antibiotika. Intervensi meningkatkan ketepatan penggunaan antibiotika (0% menjadi 67,1%), menurunkan masalah waktu pemberian (32,9% menjadi 0%), ketidaktepatan dosis (27,4% menjadi 19,2%), ketidaktepatan lama pemberian (5,5% menjadi 2,7%), masalah pemilihan obat (32,9% menjadi 11%) dan masalah indikasi (1,4% menjadi 0%). Kualitas antibiotika yang tidak rasional dengan intervensi tidak begitu berbeda pengaruhnya terhadap outcome terapi dibandingkan tanpa intervensi. Berdasarkan hasil penelitian diketahui intervensi apoteker dapat meningkatkan kualitas penggunaan antibiotika. Disarankan untuk meningkatkan kerjasama antar profesi kesehatan termasuk apoteker dan merevisi panduan penggunaan antibiotika di rumah sakit untuk meningkatkan penggunaan antibiotika yang rasional.

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Inappropriate use of antibiotics lead problems in health and patient safety. Pharmacist has responsibility to improve approppriate antibiotic usage. This study was proposed to evaluate quality of antibiotics usage in Class 3 Infection Ward, Department of Child Health, Dr. Cipto Mangunkusumo Hospital and to evaluate whether intervention of pharmacy can improve quality of antibiotics usage and therapy outcome. This is prospective study using descriptive-correlative approach from January to April 2011. Recomendations were given to prescribers to solve the problems of inappropriate antibiotics usage. A high proportion (78,82%) of 170 patient received antibiotics. Qualitative evaluation using Gyssens methode had result that about 60,4% antibiotic prescriptions were appropriate; and 39,6% were inappropriate. Length of stay, origin room, total medicine and total antibiotics used by patient have effect on quality antibiotics usage. Intervention of pharmacist improve appropriateness of antibiotics (from 0% to 67,1%), decrease timing problems (from 32,9% to 0%), dosage problems (from 27,4% to 19,2%), duration problems (from 5,5% to 2,7%), drug choice problems (from 32,9% to 11%) and indication problems (1,4% to 0%). Inappropriate used of antibiotics with intervention had no significant difference effect to outcome therapy compared with inappropriate used of antibiotics without intervention. From the result of study, it could be concluded that intervention of pharmacy can improve quality of antibiotics usage. Researcher suggests to improve teamwork of healthcare provider include pharmacy and to revise antibiotic usage guideline in order to improve approppriate antibiotic usage.

Abstrak :
Penelitian ini melakukan optimasi metode analisis penetapan kadar sisplatin secara kromatografi cair kinerja tinggi melalui derivatisasi menggunakan pereaksi dietilditiokarbamat untuk meningkatkan selektivitas dan sensitifitasnya terhadap detektor Uv-Vis, karena senyawa sisplatin tidak mempunyai gugus kromofor yang dapat terdeteksi oleh detektor ultraviolet. Menentukan kadar ondansetron hidroklorida dalam sampel dicobakan mengoptimasi penggunaan kolom fase terbalik C18 yang belum umum untuk penetapan kadar ondansetron. Sisplatin mempunyai efek samping emetogenik kuat yang dapat di hambat oleh ondansetron melalui inhibitor reseptor 5-HT3 yang sangat efektif untuk pencegahan mual dan muntah selama kemoterapi sisplatin yang diberikan secara terpisah melalui intravena. Pemberian antiemetik bersamaan dengan kemoterapi dalam satu rute pemberian diharapkan lebih efektif dan efisien untuk penanganan kemoterapi kanker. Pemberian dalam satu rute secara bersamaan harus dilakukan evaluasi stabilitas kimia campuran sisplatin dan ondansetron hidroklorida dalam satu larutan infus NaCl 0,9 % selama 24 jam kemoterapi kanker. Sisplatin dianalisis menggunakan kromatografi cair kinerja tinggi melalui derivatisasi dengan pereaksi natrium dietilditiokarbamat 10% dalam NaOH 0,2N. Derivat sisplatin-dietilditiokarbamat dielusi menggunakan fase gerak asetonitrilair (70:30 %v/v) dengan kecepatan alir 0,8 ml/menit pada kolom Knauer® C18-RP (250 x 4,6 mm, 5µm). Ondansetron hidroklorida dianalisis dan dipisahkan menggunakan kolom Sunfire Waters® C18-RP (25 cm x 4,6 mm, 5 µm) dengan fase gerak KH2PO4 50 mM (pH 7) dan asetonitril (75:25 %v/v) dengan kecepatan alir 2 ml/menit dan dideteksi pada panjang gelombang 249 nm. Stabilitas kimia kedua obat selama 24 jam dievaluasi dengan membuat campuran larutan injeksi sisplatin 92,42 ppm dan ondansetron HCl 59,15 ppm dalam larutan infus NaCl 0,9 % yang disimpan pada suhu 27°C dibawah cahaya ruangan normal. Hasil derivatisasi sisplatin dengan 20µl dietilditiokarbamat 10% pada suhu 90°C selama 20 menit diekstraksi dengan 2ml kloroform dan dideteksi pada panjang gelombang 344 nm. Metode linier pada kisaran 20 sampai 140 ppm dengan batas deteksi (LOD) 3,606 ppm dan koefisien variasi intra-hari dan interhari rata-rata < 2 % pada semua tingkat konsentrasi. Optimasi metode analisis ondansetron hidroklorida diperoleh kurva kalibrasi yang linier pada kisaran 5 sampai 100 ppm dengan batas deteksi (LOD) 3,404 ppm serta presisi intra-hari dan inter-hari dengan koefisien variasi rata-rata ≤ 2 % pada semua tingkatan konsentrasi pengujian. Hasil stabilitas kimia campuran kombinasi sisplatin dan ondansetron HCl dalam larutan infus NaCl 0,9%, diketahui sisplatin dan ondansetron HCl stabil selama 4 jam meskipun berkurangnya potensi <10% dari kedua komponen obat. Metode yang dikembangkan selektif dan spesifik untuk pemisahan dan kuantitasi penetapan sisplatin dan ondansetron HCl dari hasil uraiannya dalam satu campuran sediaan farmasi. ......This research to the optimization analysis methods of the determination of the cisplatin consentrations utilizing high performance liquid chromatography to establishment concentration of cisplatin utilizing reagents diethyldithiocarbamate to increasing it selectifity and sensitifity for ultraviolet detection, because the cisplatin compounds does not have any chromophore fungtions that can be detected by ultraviolet detector. Determine the consentration ondansetron hydrochloride in the sample we purpose optimize the use of C18 reversed phase column is not common for the determination of ondansetron consentrations. Cisplatin have any side effects strong emetogenic that it can be blocked by ondansetron via inhibitor 5-HT3 receptors which is very effective for the prevention of nausea and vomiting during cisplatin chemotherapy provided separately through intravenously. Giving antiemetic along with chemotherapy in an expected route of more effective and efficient handling of chemotherapy for cancer. Giving in a route at the same time stability evaluation should be conducted chemical mixture cisplatin and ondansetron hydrochloride in one solution infuse NaCl 0.9% during the 24 hours of cancer chemotherapy. Cisplatin was analyzed using high performance liquid chromatography through derivatisation with sodium diethyldithiocarbamate reagents in 10% NaOH 0.2 N. Derivate cisplatin-diethyldithiocarbamate was eluted using phase mobile acetonitrile-water (70:30% v/v) with the flow rate 0.8 ml / min on the Knauer ® C18-RP (250 x 4.6 mm, 5μm) column. Ondansetron hydrochloride was analyzed and separated using a Sunfire Waters ® C18-RP (25 cm x 4.6 mm, 5 μm) column with a mobile phase 50 mM KH2PO4 (pH 7) and acetonitrile (75:25% v/v) with the flow rate 2 ml / min and detected at 249 nm. Chemical stability of both drugs for 24 hours was evaluated by creating a mixture solvent injection cisplatin 92.42 ppm and 59.15 ppm ondansetron HCl solution in 0.9% NaCl infuse was stored at a temperature of 27°C under normal room light. Derivatisation results of cisplatin with 20μl diethyldithiocarbamate 10% at a temperature of 90°C for 20 minutes with 2ml chloroform extracted and detected at 344 nm. Methods was linier over the range 20 to 140 ppm with a limit of detection (LOD) 3.606 ppm and the coefficient of variation intra-day and interday average of <2% for all concentration. The ondansetron hydrochloride methods was optimized and validated with the calibration curve was linier over the range of 5 to 100 ppm with a limit of detection (LOD) 3.404 ppm. Precision intra-day and inter-day coefficients of variation average ≤ 2% for all concentration. Chemical stability results of mixture combination of cisplatin and ondansetron HCl in 0.9% NaCl infuse solution, known the cisplatin and ondansetron HCl was stable for 4 hours although loss of their potencies <10%. Methods was developed for specific and selective separation and quantitation determination of cisplatin and ondansetron HCl from its decomposition in the mixture of pharmaceutical dosage form.

Abstrak :
Pendahuluan –Diabetes Mellitus tipe 2 (DMT2) merupakan sindrom inflamasi progresif dengan peningkatan risiko komplikasi kardiovaskular berupa Atherosclerotic Cardiovascular Disease (ASCVD). Proses thromboinflamasi pada DMT2 ASCVD dikaitkan dengan perubahan pada jumlah serta fungsi leukosit dan trombosit. Rasio leukosit (Neutrophil-Lymphocyte Ratio, Monocyte-Lymphocyte Ratio, Platelet-Lymphocyte Ratio) serta penanda biologis dari netrofil (Peptydil Arginine Deiminase-4), monosit/makrofag (Interleukin-6), dan trombosit (Platelet Glycoprotein 1b-α) dikenali sebagai penanda biologis yang dapat memprediksi perubahan plak stabil dan tidak stabil pada pasien DMT2 ASCVD. Studi ini dilakukan untuk menganalisis hubungan antara klasifikasi pasien DMT2 2 risiko sangat tinggi (Very High Risk / VHR) dan risiko tinggi (High Risk / HR) dan pada pasien DMT2 dengan Acute Coronary Syndrome (ACS) terhadap parameter inflamasi NLR, MLR, PLR, GPIbα, PAD4, dan IL-6. Metodologi – 75 pasien DMT2 ACSVD yang menjalani pengobatan di rawat jalan dan unit gawat darurat Rumah Sakit Pusat Jantung dan Pembuluh Darah Harapan Kita dilibatkan dalam studi ini. Pasien dikategorikan sebagai DMT2 risiko tinggi, DMT2 risiko sangat tinggi, dan DMT2 ACS. Parameter metabolisme dan inflamasi diukur dan dianalisis pada ketiga kelompok DMT2 ASCVD tersebut. Hasil dan Diskusi – Nilai parameter metabolisme kolesterol total dan Low Density Lipoprotein (LDL) serta parameter inflamasi NLR, MLR, PLR, dan IL-6 ditemukan lebih tinggi dan signifikan pada kelompok DMT2 ACS. Nilai Gp1bα ektodomain (Glikokalisin) ditemukan lebih tinggi pada kelompok DMT2 risiko tinggi dan DMT2 risiko sangat tinggi menggambarkan hubungan Gp1bα dan ADAM17 yang terkait dengan keseimbangan pembentukan dan pembersihan trombosit. Nilai PAD4 yang lebih tinggi pada kelompok DMT2 risiko tinggi dan DMT2 risiko sangat tinggi menggambarkan proses perbaikan jaringan dan induksi polarisasi makrofag menjadi fenotip antiinflamasi yang berperan terhadap perbaikan fungsi kardiovaskular. Penelitian ini menunjukkan bahwa nilai NLR dan kolesterol total yang tinggi serta nilai PAD4 yang rendah merupakan prediktor terjadinya keadaan ACS (plak tidak stabil) pada pasien DMT2 ASCVD. ......Introduction – Diabetes Mellitus type 2 (T2DM) is a progressive inflammatory syndrome with an increased risk of cardiovascular complications in the form of Atherosclerotic Cardiovascular Disease (ASCVD). The thromboinflammatory process in T2DM ASCVD is associated with changes in the number and function of leukocytes and platelets. The leukocyte ratio (Neutrophil-Lymphocyte Ratio, Monocyte-Lymphocyte Ratio, Platelet-Lymphocyte Ratio) as well as biological markers of neutrophils (Peptydyl Arginine Deiminase-4), monocytes/macrophages (Interleukin-6), and platelets (Platelet Glycoprotein 1b-α) are recognized as a biological marker that can predict stable and unstable plaque changes in T2DM with ASCVD. This study was conducted to analyze the relationship between the classification of T2DM patients with very high risk (VHR), high risk (HR), and early onset ACS on the inflammatory parameters NLR, MLR, PLR, GPIbα, PAD4, and IL-6. Methodology – This study included 75 ACSVD T2DM patients being treated at Harapan Kita Heart and Blood Vessel Center Hospital's outpatien and emergency unit. Patients were classified as having high risk T2DM, extremely high risk T2DM, or ACS T2DM. In the three T2DM ASCVD groups, metabolic and inflammatory parameters were evaluated and studied. Results and Discussion – The metabolic indices total cholesterol and Low Density Lipoprotein (LDL), as well as the inflammatory markers NLR, MLR, PLR, and IL-6, were shown to be greater and significant in the T2DM ACS group. Gp1b ectodomain (Glycocalysin) values were found to be greater in the high risk T2DM and very high risk T2DM groups, demonstrating the relationship between Gp1b and ADAM17, which is associated to platelet production and clearance balance. Higher PAD4 values in the high risk T2DM and very high risk T2DM groups represent tissue repair and the activation of macrophage polarization into an anti-inflammatory phenotype, which contributes to improved cardiovascular function. According to this study, high NLR and total cholesterol levels, as well as low PAD4 levels, are predictors of ACS (unstable plaque) in ASCVD T2DM patients.

Abstrak :
Arginase (L-arginine ureahydrolase) adalah enzim yang berperan dalam siklus urea. Arginase juga memainkan peran penting dalam produksi nitrat oksida (NO). Gangguan keseimbangan NO merupakan kontributor terjadinya gangguan fungsi endotel pembuluh darah. Senyawa fenol dan flavonoid diketahui mempunyai aktivitas penghambatan arginase. Genus Sterculia kaya dengan senyawa fenol dan flavonoid. Penelitian ini bertujuan untuk mendapatkan senyawa dari tanaman genus Sterculia yang mempunyai aktivitas penghambatan arginase. Penelitian diawali dengan skrining dari 5 tanaman genus Sterculia yaitu: S. macrophylla, S. comosa, S.parkinsonii, S.rubiginosa, S.stipulata. Bagian yang digunakan adalah daun dan kayu. Ekstrak diuji aktivitas inhibitor enzim arginase dan antioksidan dengan metode DPPH dan FRAP. Ekstrak yang aktif adalah ekstrak metanol kayu Sterculia comosa dan ekstrak metanol kayu Sterculia macrophylla. Ekstrak aktif dipisahkan dengan kromatografi kolom vakum menjadi fraksi. Tiap fraksi di uji aktivitas inhibitor enzim arginase dan antioksidan dengan metode FRAP dan DPPH. Fraksi dilanjutkan diisolasi menggunakan kromatografi kolom dan Kromatografi Lapis Tipis Preparatif sampai didapatkan isolat. Hasil isolat diidentifikasi dengan FTIR, 1H-NMR,13C-NMR, HSQC, HMQC, HMBC, LCMSMS. Sterculia comosa (kayu comosa/KC) didapatkan isolat KC4.4.6 asam (-)-2-(E)-kafeoil-D-gliserat, dan KC4.4.5.1 adalah asam trans-isoferulat, yang merupakan turunan sinamat. Sterculia macrophylla (kayu macrophylla/KM) diperoleh senyawa senyawa KM3.9.1 merupakan 3β-5α,6α-epoksi-3-hidroksi-7-megastigmen-9-on. Senyawa KM3.5.M merupakan asam pikolinat, dan Senyawa KM-1 merupakan campuran β-sitosterol dan stigmasterol. Hasil uji aktivitas inhibitor enzim arginase diperoleh nilai IC50 untuk isolat KM3.9.1: 59,31μg/ml, KM3.5.M: 73,98 μg/ml, KC4.4.6: 98,03 μg/ml, KC4.4.5.1: 292,58 μg/ml, dan KM1: 140,56 μg/ml, kontrol positif nor-NOHA: 3,97 μg/ml. Aktivitas antioksidan metode DPPH didapatkan nilai IC50 isolat KM3.9.1:92,60 μg/ml, KM3.5.M: 106,42 μg/ml, KC4.4.6: 48,77 μg/ml, KC4.4.5.1: 88,08 μg/ml dan KM1: 185,09 μg/ml, kontrol positif kuersetin: 5,63 μg/ml. Aktivitas antioksidan dengan metode FRAP KM3.9.1: 10,76 FeEAC (Mol/g), KM3.5.M: 5,79 FeEAC (Mol/g), KC4.4.6: 16,40 FeEAC (Mol/g), KC4.4.5.1: 15,79 FeEAC (Mol/g) KM-1: 11,89 FeEAC (Mol/g), kontrol positif kuersetin: 1201,61 FeEAC (Mol/g). Isolat KM3.9.1 (3β-5α,6α-epoksi-3-hidroksi-7-megastigmen-9- on) merupakan senyawa yang mempunyai aktivitas sebagai inhibitor enzim yang paling baik, sedangkan aktivitas antioksidan yang paling baik adalah isolat KC4.4.6/asam ()-2-(E)-kafeoil-D-gliserat Arginase (L-arginine urea-hydrolase) is an enzyme that plays a role in the urea cycle. Arginase also plays an essential role in the production of Nitric Oxide (NO). NO balance disorder is a contributor to the impaired endothelial function of blood vessels. Phenol and flavonoid compounds are known to have arginase inhibitory activity. The genus Sterculia contains rich of phenol compounds and flavonoids. This study aims to obtain compounds from the genus Sterculia which have arginase inhibitory activity. The study began with the screening of five plants of Sterculia genus: S. macrophylla, S. comosa, S.parkinsonii, S.rubiginosa, S.stipulata. The parts used are leaves and wood. The extract tested for the activity of arginase inhibitory activity and antioxidant by DPPH and FRAP methods. The active extracts were methanol extract of Sterculia comosa wood and methanol extract of Sterculia macrophylla wood. The active extract was separated by vacuum column chromatography into fractions. Each fraction tested for the activity of arginase inhibitory and antioxidant by the FRAP and DPPH methods. The fraction isolated using column chromatography and Preparative Thin Layer Chromatography until isolates obtained. The isolates identified with FTIR, 1H-NMR,13C-NMR, HSQC, HMQC, HMBC, LCMSMS. Sterculia comosa (comosa woods/KC) obtained isolates KC4.4.6/(-)-2-(E)-caffeoyl-D-glyceric acid., KC4.4.5.1 trans-isoferrulic acid, which are cinnamic. Sterculia macrophylla (comosa woods/KC) obtained compound: KM3.9.1 is a compound of 3β-5α,6α-epoxy-3-hydroxy-7- megastigmen-9-one. KM3.5.M is picolinic acid, and KM1 is β-sitosterol and stigmasterol. The results of arginase enzyme inhibitor activity obtained IC50 values for isolates KM3.9.1: 59.31 μg/ml, KM3.5.M: 73.98 μg/ml, KC4.4.6: 98.03 μg/ml, KC4.4.5.1: 292.58 μg/ml, and KM1: 140.56 μl/ml, positive control of nor-NOHA: 3.97 μg/ml. Antioxidant activity DPPH method obtained IC50 isolates KM3.9.1: 92.60 μg/ml, KM3.5.M: 106.42 μg/ml, KC4.4.6: 48.77 μg/ml, KC4.4.5.1: 88,08 μg/ml and KM1: 185.09 μg/ml. Quercetine as positive control: 5.63 μg/ml. Antioxidant activity with FRAP method KM3.9.1: 10.76 FeEAC (Mol/g), KM3.5.M: 5.79 FeEAC (Mol/g), KC4.4.6 of 16.40 FeEAC (Mol/g), KC4.4.5.1: 15.79 FeEAC (Mol/g) KM1: 11.89 FeEAC (Mol/g), quercetine: 1201.61 FeEAC (Mol/g). KM3.91 (3β-5α,6α-epoxy-3-hydroxy-7-megastigmen-9-one) isolates was compound that have the best activity as enzyme inhibitor, while the best antioxidant activity was KC4.4.6/()-2-(E)-caffeoyl-D-glyceric acid.

Abstrak :

Rubus fraxinifolius dan R. rosifolius merupakan tanaman Rubus yang dapat ditemukan di daerah pegunungan Indonesia. Kedua tanaman memiliki morfologi buah yang mirip yaitu berbentuk berry merah dan edible, serta mengandung senyawa golongan triterpenoid, polifenol dan flavonoid.  Beberapa spesies Rubus dilaporkan memiliki aktivitas sebagai antiaging yaitu antielastase, antioksidan, dan antitirosinase. Penelitian ini bertujuan untuk menelaah aktivitas antiaging secara in vitro pada ekstrak dan isolat dari tanaman R. fraxinifolius dan R. rosifolius. Batang, buah, dan daun kedua tanaman diekstraksi menggunakan alat Soxhlet serta dilakukan skrining aktivitas anti elastase dan antioksidan.  Selanjutnya terhadap ekstrak terpilih dilakukan pemisahan, fraksinasi dan isolasi senyawa. Isolat yang didapat diidentifikasi menggunakan spektrometri FTIR, ¹H-NMR, ¹³C-NMR, DEPT, HSQC, HMQC, HMBC, dan LC-MS, serta diuji aktivitas antielastase, antitirosinase dan sitotoksisitas pada sel fibroblast secara in vitro. Hasil ekstraksi bertingkat menunjukkan bahwa ekstrak metanol daun R. fraxinifolius memiliki aktivitas antielastase dan antioksidan tertinggi dengan masing-masing IC₅₀ 57,45 dan 4,33 µg/ml. Terhadap fraksi metanol daun R. fraxinifolius (DFM) dilakukan pemisahan menggunakan kromatografi cair vakum dan diperoleh 11 fraksi. Uji antielastase fraksi menunjukkan fraksi paling aktif adalah DFM8. Selanjutnya dilakukan isolasi lebih lanjut terhadap DFM8 dan diperoleh 3 isolat. Hasil elusidasi struktur menunjukkan bahwa ketiga isolat merupakan suatu triterpen pentasiklik tipe ursan. Hasil telaah data pengujian DEPT, HMQC, HSQC, HMBC serta IR dan MS disimpulkan senyawa DFM 8a adalah asam 2,3-glikol, 19α-hidroksi-12-ursen-23,28-dioat (C₃₂H₄₈O₇, BM 544); DFM8b asam 2,3-propanandiol, 19α-hidroksi-12-ursen-28-oat (C₃₃H₅₂O₅, BM 528,38); dan DFM8c asam 2,3-glikol-19α-hidroksi-23,24-nor-12-ursen-28-oat (C₃₀H₄₆O₅, BM 486,33). Ketiga senyawa hasil isolasi ini merupakan senyawa baru dan belum pernah ditemukan sebelumnya. Uji aktivitas antielastase senyawa DFM8a, DFM8b, dan DFM8c memiliki IC₅₀ berturut-turut adalah 122,199; 98,22; dan 54,33 µg/ml, serta antitirosinase dengan IC₅₀ 207,8; 221,5; dan 335,9 µg/ml. Uji toksisitas menunjukkan bahwa ekstrak DFM, fraksi DFM8, dan isolat DFM8b tidak toksik terhadap sel fibroblas NIH/3T3.

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Rubus fraxinifolius and R. rosifolius are Rubus genus, which can be found in the mountain of Indonesia. Both plants have similar fruit morphology: red and edible berries and contain triterpenoid, polyphenols, and flavonoids. Some species of Rubus are reported to have antiaging activity, antielastase, antioxidant, and antityrosinase. This study aims to examine the in vitro antiaging activity of extracts and isolated compounds from R. fraxinifolius and R. rosifolius. The stems, fruits, and leaves of both plants were extracted and screened for antielastase and antioxidant activity. Furthermore, the selected extracts were separated, fractionated, and isolated to yield isolates. The obtained isolates were identified using FTIR spectrometry, ¹H-NMR, ¹³C-NMR, DEPT, HSQC, HMQC, HMBC, and LC-MS, and also were tested for antielastase, antityrosinase, and cytotoxicity activities in fibroblast cells. The continuous extraction results showed that the methanol extract of R. fraxinifolius leaves had the highest antielastase and antioxidant activity with IC₅₀ 57.45 ppm and 4.33 ppm, respectively. The methanol fraction of R. fraxinifolius (DFM) leaves were separated using vacuum liquid chromatography and obtained 11 fractions. The antielastase assay of fractions gave the most active fraction was DFM8. Then, further isolation of DFM8 was carried out, and three isolates were obtained. The structural elucidation showed that the three isolates were ursane-type of pentacyclic triterpenes. The results of DEPT, HMQC, HSQC, HMBC, IR and MS spectrometry test concluded that the compound DFM 8a was 2,3-glycol, 19α-hydroxy-12-ursen-23,28-dioic acid (C₃₂H₄₈O₇, MW 544); DFM8b 2,3-propanandiol, 19α-hydroxy-12-ursen-28-oic acid (C₃₃H₅₂O₅, MW 528.38); and DFM8c 2,3-glycol-19α-hydroxy-23,24-nor-urs-12-en-28-oic acid (C₃₀H₄₆O₅, MW 486.33). All isolated compounds are new compounds and have never been found before. The IC₅₀ of antielastase activity of DFM8a, DFM8b, and DFM8c were 122.199; 98.22; and 54.33 ppm, respectively, and the IC₅₀ of antityrosinase activity were 207.8; 221.5; and 335.9 ppm, respectively. Toxicity tests showed that the DFM extract, the DFM8 fraction, and the DFM8b were not toxic to NIH/3T3 fibroblast cells.

Abstrak :
Peningkatan kebutuhan akan kosmetik saat ini berdampak terhadap meningkatnya tuntutan ketersediaan bahan baku kosmetik. Tanaman Soka Jawa (Ixora javanica) merupakan salah satu tanaman yang telah diteliti baik kandungan senyawa dan aktivitasnya, terutama bagian bunganya dan dapat digunakan sebagai kandidat bahan baku alami sediaan kosmetik. Disertasi ini bertujuan mengembangkan metode ekstraksi yang ramah lingkungan terhadap bunga Soka Jawa dalam rangka memperoleh sediaan kosmetik skin-lightening dan antioksidan yang berkualitas, aman dan efektif. Metode ekstraksi yang dikembangkan menerapkan prinsip green extraction menggunakan Deep Eutectic Solvent (DES) sebagai alternatif pelarut dan metode Ultrasound-assisted Extraction (UAE). Penelitian disertasi ini dilakukan secara eksperimental yang secara garis besar terbagi menjadi empat tahap penelitian yaitu tahapan skrining DES, optimalisasi kondisi ekstraksi, formulasi dan selanjutnya tahap evaluasi sediaan. Pada tahapan skrining DES, kombinasi kolin klorida dan propilen glikol (perbandingan molar 1:1) memberikan hasil perolehan senyawa serta aktivitas yang relatif paling tinggi dibanding pelarut yang lain sehingga dipilih untuk pelarut pengekstraksi bunga Soka Jawa. Hasil optimalisasi dengan bantuan statistik Response surface methodology (RSM) menunjukkan bahwa waktu ekstraksi 40 menit, penambahan air 25%, dan solid-to-liquid ratio 1:27 g/mL merupakan kondisi optimal untuk ekstraksi bunga Soka Jawa menggunakan DES terpilih dengan metode UAE. Ekstraksi pada kondisi optimal tersebut juga terbukti lebih efisien dibandingkan dengan pelarut etanol. Ekstrak DES bunga Soka Jawa yang diperoleh langsung diformulasi menjadi sediaan krim tanpa melalui proses pemekatan ekstrak. Hasil evaluasi terhadap sediaan krim menunjukkan bahwa sediaan krim yang diperoleh memenuhi spesifikasi sediaan dan terbukti stabil secara fisik, kimia, dan mikrobiologi. Berdasarkan hasil penelitian secara menyeluruh, dapat disimpulkan bahwa penelitian disertasi ini tidak hanya berhasil mengembangkan green extraction untuk ekstraksi bunga Soka Jawa namun juga memperoleh suatu ekstrak DES bunga Soka Jawa yang optimal sebagai bahan utama sediaan krim skin-lightening dan antioksidan yang berkualitas serta efektif dan aman secara in silico. ......The increasing demand for cosmetics has resulted in increasing of the need for cosmetic raw materials. Soka Jawa (Ixora javanica) is one of the plants that has been studied for its phytochemical and bioactivity, especially its flower and can be used as a candidate for natural raw materials for cosmetic preparations. The aim of this study is to develop an environmentally friendly extraction method for Soka Jawa flower in order to obtain quality, safe and effective skin-lightening and antioxidant cosmetic preparations. The developed extraction method applied the green extraction principle of using Deep Eutectic Solvent (DES) as an alternative solvent and Ultrasound-assisted Extraction (UAE) method. The main stages of this experimental study were DES screening, extraction methods optimization, cream preparation and its evaluation. The combination of choline chloride and propylene glycol (molar ratio of 1:1) showed the highest compound yield and activity compared to other solvents, therefore it was chosen as extraction solvent for Ixora flowers. The extraction method optimization using the Response Surface Method (RSM) showed that the extraction time of 40 minutes, the addition of 25% water, and a solid-to-liquid ratio of 1:27 g/mL were the optimal conditions for the extraction of Soka Jawa flowers using selected DES with the UAE method. The extract obtained under optimum extraction conditions showed higher extraction yields and activity than ethanolic extract which was used for comparison. The Ixora flower extract obtained was directly formulated into a cream preparation without going through the extract evaporation. The results of the evaluation of all parameters showed that the cream met the specifications and also proved to be physically, chemically, and microbiologically stable. In brief, it can be concluded that this study is not only succeeded in developing a green extraction method for Ixora flowers but also obtained an optimal DES extract of Ixora flowers as the main raw material for high quality skin-lightening and antioxidants cream preparations, and also predicted safe and effective in silico.