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"ABSTRACTThree types of cyclopentanone derivatives have been synthesized from aromatic aldehyde and ketone derivatives undera base condition through aldol condensation. These cyclopentanone products were 2,5-dibenzylidene-cyclopentanone (a), 2,5-bis-(4-hydroxy-benzylidene)-cyclopentanone (b),and 2,5-bis-(4-hydroxy-benzylidene)-cyclopentanone (c)which has a yield of 63-99%. The chemical structure of these compounds were determined using UV, IR and NMRspectroscopy. In order to clarify the role of hydroxyl and amine moieties, toxic, antioxidant and anti-inflammatoryactivities were carried out. The toxic test indicated that thecompounds showed strong toxicity. In addition, the presenceof hydroxyl and amine groups on both rings of curcumin increased the antioxidant and anti-inflammatory activities."

"Asam salisilat memiliki aktivitas anti-inflamasi dan antioksidan, namun dapat menimbulkan efek samping pada saluran cerna. Modifikasi gugus karboksilat senyawa tersebut menjadi turunan amida dapat menjadi solusi untuk mengatasi kekurangannya. Pada penelitian ini dilakukan sintesis senyawa analog salisilamida, 2‐hidroksi‐N‐(piridin‐2‐il)benzamida (1) dan turunan basa Mannich-nya (2a-f). Berdasarkan hasil uji aktivitas anti-inflamasi in vitro dengan metode penghambatan denaturasi protein, senyawa hasil sintesis menunjukkan aktivitas anti-inflamasi dengan hasil uji IC50 pada rentang = 0,118-0,434 mM. Aktivitas tersebut lebih rendah dibandingkan piroksikam yang digunakan sebagai senyawa standar (IC50 = 0,0073 mM). Senyawa 2e, 2‐hidroksi‐N‐(piridin‐2‐il)benzamida tersubstitusi basa Mannich 2,6-dimetilmorfolin merupakan senyawa paling tinggi aktivitasnya. Energi ikatan (DG) yang diperoleh dari studi penambatan molekul adalah -8,49 kkal/mol pada reseptor COX-1 (PDB ID: 1EQG) dan -8,92 kkal/mol pada reseptor COX-2 (PDB ID: 5KIR). Pengujian antioksidan dengan metode DPPH diperoleh rentang IC50 = 0,63-12,90 mM, sedangkan dengan metode FRAP diperoleh EC50 antara 0,68-0,91 mM. Semua senyawa hasil sintesis memiliki aktivitas antioksidan lebih rendah dibandingkan dengan standar asam askorbat (metode DPPH, IC50= 0,0021 mM; metode FRAP, EC50= 0,008 mM).

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Salicylic acid is a natural active substance known to have anti-inflammatory and antioxidant activity, but it has side effects in gastrointestinal tract. The modification of its carboxylic groups into amide derivatives can be a solution to overcome its weakness. In this study we synthesized salicylamide analog, 2‐hydroxy‐N‐(pyridine‐2-yl)benzamide (1) and its Mannich base derivatives (2a-f). Based on an in-vitro anti-inflammatory activity test using the inhibition protein denaturation method, the synthesized compounds showed anti-inflammatory activity. The IC50 obtained was in the range of 0.118-0.434 mM. The activity was lower than piroxicam used as a standard compound (IC50 = 0.0073 mM). Compound 2e, 2‐hydroxy‐N‐(pyridine‐2-yl)benzamide substituted by 2,6-dimethylmorpholin Mannich base, showed the highest activity with IC50= 1.18 mM. The binding energy (DG) obtained from molecular docking study was -8.49 kcal/mol and -8.92 kcal/mol for COX-1 and COX-2 receptors (PDB ID: 1EQG and 5KIR) protein target respectively. The antioxidant activity using DPPH test was obtained with IC50 in the range of 0.63-12.90 mM, while using the FRAP method EC50 in the range of 0.68-0.91 mM. All the synthesized compounds had lower antioxidant activity than ascorbic acid used as a standard (DPPH method, IC50 = 0.0021 mM; FRAP methode, EC50 = 0.008 mM)"

"Objective: Garcinia xanthochymus extract has been reported to have several pharmacological properties. This studywas conducted to evaluate cytotoxic and anti-inflammatory activities of G. xanthochymus extracts on cell lines.Methods: The roots and stem barks of plant were extracted using maceration method with n-hexane, dichloromethaneand methanol, successively. Cytotoxic activity of the extracts was tested against MCF-7 breast adenocarcinoma usingMTT assay. Anti-inflammatory study was evaluated using RAW 264.7 mouse macrophage cells. The nitric oxideproduction in LPS-stimulated cells was measured using Griess reagent. Results: The results of cytotoxic and antiinflammatorystudy showed that dichloromethane and n-hexane extracts of root and stem bark exhibited cytotoxicactivity in dose-dependent manner. Meanwhile, for anti-inflammatory study, all root extracts together with stem barkdichloromethane and n-hexane extracts reduce NO production in LPS-stimulated cells in dose dependent manner.Conclusions: This finding indicated that G. xanthochymus extracts might become interesting candidate for treatment ofcancer and inflammation."

"Obat antiinflamasi didefinisikan sebagai golongan obat yang memiliki aktivitas menekan atau mengurangi peradangan, terutama obat antiinflamasi non steorid. Salah satu efek samping dari obat antiinflamasi non steroid adalah menyebabkan penyakit tukak lambung. Penyakit tukak lambung yang disebabkan oleh obat antiinflamasi dapat diobati dengan propolis. Di samping memiliki sifat anti tukak lambung, beberapa penelitian luar negeri mengatakan bahwa propolis memiliki efek antiinflamasi. Tujuan dari penelitian ini adalah mengidentifikasi sifat antiinflamasi propolis lokal, beserta molekul penandanya. Propolis yang digunakan dalam penelitian ini adalah propolis lebah tak bersengat dari daerah Sulawesi Selatan yaitu Tetragronula sp, dengan spesifikasi propolis padatan dan karang. Penelitian mengenai efek antiinflamasi dari propolis menggunakan metode in vivo dengan hewan uji tikus jantan sprague dawley. Metode ini menggunakan karagenan sebagai zat penginduksi inflamasi dan natrium diklofenak 135 mg/kg sebagai kontrol positif. Dosis yang akan diberikan adalah 50 mg/kg, 100 mg/kg, dan 200 mg/kg untuk propolis padatan, serta 25 mg/kg, 50 mg/kg, dan 100 mg/kg untuk propolis karang. Data diolah dengan statistik ANOVA satu arah dan Kruskall Wallis, dengan program SPSS 23.0. Hasil dari pengukuran sampel dengan metode LC-MS didapatkan grafik kromatogram dan spektra massa yang datanya diolah menggunakan program MassLynx 4.1. Hasil penelitian menunjukkan propolis padatan dengan dosis 50 mg/kg memiliki daya antiinflamasi yang paling baik sebesar 61,81 , yang disusul dengan propolis karang dosis 25 mg/kg dengan daya antiinflamasi 58,12 . Dengan metode LC-MS/MS, berhasil diidentifikasi 7 senyawa yang memiliki potensi sebagai molekul penanda antiinflamasi pada propolis padatan dan karang. Senyawa [6]-dehidrogingerdion, alfa-tokoferol suksinat, adiperforin, 6-epiangustifolin ditemukan pada kedua propolis. Senyawa deoksipodofilotoksin dan kurarinon ditemukan pada propolis padatan, serta xantoxiletin ditemukan pada propolis karang.

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Antiinflammatory drug are types of drug that have abilities to inhibit or reduced an inflammation, especially Non Steroidal Antiinflammatory Drugs NSAID . One of side effect of using the non steroid type is causing ulcerogenic disease. Ulcerogenic disease that caused by the antiinflammatory drug can be cured by propolis. Beside having an ability to cure ulcerogenic disease, propolis have the ability to cure an inflammation according to some international studies. The research main purpose are to identify antiinflammatory properties of Indonesian propolis and also the biomarkers. The propolis that used in this research were the one from stingless bee that can be found in South Sulawesi, Indonesia, which was Tetragronula sp and 2 types of propolis that used were smooth and rough propolis. The method that used to identify propolis anti inflammatory properties was in vivo method with sprague dawley white rat as the tested animal. In this method, inflammation was induced by carrageenan and 135 mg kg diclofenac sodium was used as positive control.

Dose of propolis that used in this research were 50 mg kg, 100 mg kg, 200 mg kg for smooth propolis and 25 mg kg, 50 mg kg, 100 mg kg for rough propolis. The measurement data was analyzed with One Way ANOVA and Kruskall Wallis statistical test in SPSS 23.0. After that, to identified antiinflammatory molecule marker in Propolis, LC MS MS method was used. From LC MS MS, chromatogram graph and mass spectra of the compounds would be gotten. The result of this method was analyzed by MassLynx 4.1. program. The result from this research indicated smooth propolis with dose 50 mg kg had the the best inflammatory inhibition and the value was 61,81 . In addition, rough propolis with dose 25 mg kg was the best dose after soft propolis with dose 50 mg kg and the value was 58,12 . Therefore, based on those result, both propolis had antiinflammatory effect. Moreover, if soft and rough propolis were compared in the same dose, soft propolis had more significant inflammatory inhibition than rough propolis. From LC MS MS result, 7 antiinflammatory compounds were identified as the potential antiinflammatory biomarker in propolis. 6 dehydrogingerdione, alpha tocopherol succinate, adhyperforin, and 6 epiangustifolin were identified in smooth and rough propolis. Deoxypodophyllotoxin and kurarinone were identified in smooth propolis. Meanwile xanthoxyletin was identified in rough propolis."

"Propolis merupakan suatu campuran resin alami yang dikumpulkan lebah dari berbagai tanaman yang dihinggapinya. Umumnya, propolis dihasilkan dalam jumlah yang banyak oleh lebah yang tidak bersengat dibandingkan lebah yang bersengat. Di Indonesia, diketahui bahwa daerah Kalimantan, terutama Kalimantan Selatan, merupakan daerah dengan variasi spesies lebah tidak bersengat tertinggi. Pada penelitian ini, dipilih tiga sampel propolis dari spesies lebah Heterotrigona itama, Geniotrigona thoracica, dan Tetragonula laeviceps asal Kalimantan Selatan. Pemilihan spesies lebah ini dilakukan berdasarkan data persebaran lebah di Indonesia yang dimiliki oleh Asosiasi Perlebahan Indonesia (API). Variasi asal daerah lebah penghasil propolis dan spesies lebah dapat menyebabkan kandungan senyawa kimia pada propolis sangat beragam. Adanya keragaman kandungan senyawa kimia pada setiap propolis akan menyebabkan senyawa bioaktif antiinflamasi yang terdeteksi juga berbeda. Oleh karena itu dilakukan identifikasi senyawa bioaktif antiinflamasi melalui pendekatan metabolomik yang mengkombinasikan metode analisis kimia dengan analisis statistik. Identifikasi senyawa metabolit secara umum dilakukan menggunakan instrumen LCMS/MS dan kemudian dipilih sembilan senyawa yang berpotensi sebagai senyawa bioaktif antiinflamasi. Identifikasi senyawa yang berperan signifikan dalam aktivitas antiinflamasi dilakukan dengan analisis statistik multivariat menggunakan data senyawa potensi bioaktif antiinflamasi dan nilai IC50 sampel propolis. Hasil penelitian ini adalah diperoleh senyawa 18-β-Glycyrrhetinic acid sebagai senyawa bioaktif antiinflamasi propolis Indonesia.

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Propolis is a natural resin mixture that bees collect from the various plants they inhabit. Generally, propolis is produced in greater quantities by stingless bees than stingless bees. In Indonesia, it is known that Kalimantan, especially South Kalimantan, is an area with the highest variety of stingless bee species. In this study, three propolis samples were selected from the bee species Heterotrigona itama, Geniotrigona thoracica, and Tetragonula laeviceps from South Kalimantan. The selection of bee species is based on data on the distribution of bees in Indonesia owned by the Indonesian Beekeeping Association (API). Variations in the origin of the propolis-producing bees and bee species can cause the content of chemical compounds in propolis to vary widely. The diversity of chemical compounds in each propolis will cause the detected anti-inflammatory bioactive compounds to be different. Therefore, identification of anti-inflammatory bioactive compounds was carried out through a metabolomics approach that combined chemical analysis methods with statistical analysis. Identification of metabolites in general was carried out using the LCMS/MS instrument and then nine compounds were selected as potential anti-inflammatory bioactive compounds. Identification of compounds that play a significant role in anti-inflammatory activity was carried out by multivariate statistical analysis using data on potential anti-inflammatory bioactive compounds and IC50 values of propolis samples. The results of this study were obtained by the compound 18-β-Glycyrrhetinic acid as an anti-inflammatory bioactive compound in Indonesian propolis."

"Nyeri neuropatik merupakan rasa sakit akibat gangguan susunan saraf dengan prevalensi penderita sekitar 7 hingga 10 persen populasi dunia. Pengobatan alternatif menggunakan jamu herbal diajukan sebagai pengobatan minim efek samping dan harga terjangkau. Pada penelitian ini, akan dilakukan perbandingan fenolik pada ekstrak cair dan padat Jamu Turun Tegang Saraf (TTS) yang terbuat dari pala (Myristica fragrans), cengkeh (Syzyangium aromaticum) dan jahe (Zingiber officinale) serta pengujian in silico aktivitas antiinflamasi senyawa aktif jamu. Ekstrak cair dihasilkan dari refluks air bahan segar dan bubuk simplisia sedangkan bubuk ekstrak dihasilkan dari pengeringan oven dan pengeringan beku. Total fenolik pada ekstrak cair bahan segar dan bubuk simplisia tertinggi diperoleh sebesar 298,5 mg GAE per L dan 983,3 mg GAE/L pada konsentrasi 100.000 ppm. Total fenolik pada bubuk ekstrak pengeringan oven dan pengeringan beku diperoleh 281,7 mg GAE per L dan 999,6 mg GAE per L. Analisis LC MS ekstrak jamu menunjukkan adanya senyawa seperti gingerol, shogaol, myristicin, eugenol, adenine, dan chlorogenic acid. Pengeringan baik oven dan pengeringan beku menurunkan luas area pada senyawa aktif, tetapi pengeringan beku memiliki pengaruh penurunan lebih kecil. Berdasarkan pengujian in silico menggunakan perangkat lunak MOE, didapatkan hasil berupa afinitas pengikatan yang tinggi antara senyawa aktif Jamu TTS sebagai ligan termodifikasi dengan protein siklooksigenase (COX 1 dan COX 2) sebagai penyebab inflamasi.

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Neuropathic pain is pain due to nervous system disorders with a prevalence of sufferers around 7 to 10 percent of the world's population. Alternative medicine using herbal medicine is proposed as a treatment with minimal side effects and affordable prices. In this study, a comparison of phenolics will be carried out on liquid and solid extracts of Jamu Neuropathic Pain Reducer (NPR) made from nutmeg (Myristica fragrans), cloves (Syzyangium aromaticum) and ginger (Zingiber officinale) as well as in silico testing of anti-inflammatory activity of active compounds of herbs. The liquid extract is produced from water reflux of fresh material and simplisia powder while the extract powder is produced from oven drying and freeze drying. The highest total phenolics in fresh ingredient liquid extract and simplisia powder were obtained at 298.5 mg GAE per L and 983.3 mg GAE per L at a concentration of 100,000 ppm. Total phenolics in oven drying and freeze-drying extract powder obtained 281.7 mg GAE per L and 999.6 mg GAE per L. LC MS analysis of herbal extracts showed the presence of compounds such as gingerol, shogaol, myristicin, eugenol, adenine, and chlorogenic acid. Both oven drying and freeze drying decrease the area of the active compound, but freeze drying has a smaller decreasing effect. Based on molecular docking simulations using MOE software, results were obtained in the form of high binding affinity between the active compound of Jamu NPR as a modified ligand with cyclooxygenase proteins (COX 1 and COX 2) as the key role in inflammation."

"Kurkumin merupakan senyawa aktif yang diisolasi dari Curcuma longa dan memiliki aktivitas sebagai antiinflamasi. Namun, senyawa ini memiliki bioavailabilitas oral yang rendah. Masalah ini dapat diatasi dengan memformulasikan kurkumin dalam nanoemulsi melalui rute pemberian injeksi intravena. Penelitian ini bertujuan untuk memperoleh sediaan injeksi nanoemulsi kurkumin yang memenuhi persyaratan sediaan parenteral serta stabilitas yang baik secara fisikoimia dan menegtahui efektivitas sediaan parenteral naneomulsi kurkumin pada hewan model inflamasi.Pada penelitian ini terdapat enam formula dengan variasi tiga konsentrasi surfaktan (1,8%; 2,4%; dan 3%) dan dua konsentrasi kurkumin (1% dan 3%). Formula di evaluasi ukuran partikel, indeks polidispersitas, potensial zeta, viskositas, pH, entrapment efficiency (EE), osmolalitas, sterilitas, dan morfologi partikel. Pada uji antiinflamasi, digunakan Formula 3 (F3) dengan dosis 20 mg/kg BB dan 40 mg/kg BB yang diberikan secara intravena kemudian kontrol pembanding deberikan melalui rute oral dengan dosis 40 mg/kg BB dan 200 mg/kg BB. Evaluasi efektivitas aktivitas antiinflmasi sediaan uji pada tikus yang diinduksi 0,2 mL karagenan 1%. Hasil penelitian didapatkan F3 dengan ukuran partikel 322,67±11,26 nm; potensial zeta -41,2±0,98 mV; PdI 0,13±0,01; efisiensi penjerapan 96,56±1,01%; pH 6,05±0,05; dan viskositas 6,63±0,25 merupakan formula terbaik yang dilanjutkan untuk uji aktivitas antiinflamasi. Studi aktivitas antiinflamasi menghasilkan kelompok 4 rute IV dosis 40 mg/kg BB menunjukkan persentase penghambatan pembengkakan hampir serupa dengan injeksi ketorolak 2,7 mg/kg BB. Formula sediaan nanoemulsi kurkumin yang menunjukkan stabilitas yang baik selama 3 bulan dan memenuhi persyaratan sediaan steril yaitu F3. Sediaan nanoemulsi kurkumin secara efektif dapat menurunkan volume edema dan diameter telapak kaki tikus Sprague Dawley yang diinduksi 0,2 mL karagenan 1% pada pemberian dosis 40 mg/kg BB.

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Curcumin is the main active compound isolated from Curcuma longa which has anti-inflammatory activity. However, this compound has low oral bioavailability. This problem can be overcome by formulating curcumin in nanoemulsis through intravenous injection. This study aims to obtain curcumin nanoemulsi injection preparations that meet the requirements for parenteral preparations as well as good physicochemical stability and to determine the effectiveness of curcumin nanoemulsi parenteral preparations in animal models of inflammation. In this study there were six formulas with variations of three concentrations of surfactants (1,8%; 2,4%; and 3%) and two concentrations of curcumin (1% and 3%). The formula was evaluated for particle size, polydispersity index, zeta potential, viscosity, pH, entrapment efficiency (EE), osmolality, sterility, and particle morphology. In the anti-inflammatory test, Formula 3 (F3) was used at a dose of 20 mg/kg BW and 40 mg/kg BW which was given intravenously then a comparison control was administered via the oral route at a dose of 40 mg/kg BW and 200 mg/kg BW. Evaluation of the effectiveness of the anti-inflammatory activity of the test preparations in rats induced by 0,2 mL of 1% carrageenan. Monitored the volume of the paws of rats using a plestimometer.The results of the study obtained F3 with a particle size of 322,67 ± 11,26 nm; zeta potential -41,2±0,98 mV; polydisperity index 0,13±0,01; adsorption efficiency of 96,56 ± 1,01%; pH 6,05 ± 0,05;viscosity 6,63 ± 0,25 was the best formula which was continued for antiinflammatory activity tests. The study of anti-inflammatory activity showed that group IV 40 mg/kg BW showed almost the same percentage of swelling inhibition as ketorolac injection of 2,7 mg/kg BW. The formula for curcumin nanoemulsi showed good stability for 3 months and met the requirements for sterile preparations, namely F3. Curcumin nanoemulsi preparations can effectively reduce the volume of edema and paw diameter of Sprague Dawley rats induced by 0,2 mL carrageenan 1% at a dose of 40 mg/kgBW."

"Penyakit inflamasi usus atau Inflammatory Bowel Disease (IBD) merupakan penyakit peradangan yang terjadi pada kolon, penyakit ini sebaiknya diobati dengan sistem penghantaran obat tertarget pada bagian spesifik. Sistem penghantaran yang ditargetkan untuk pengobatan IBD dirancang untuk meningkatkan konsentrasi obat pada jaringan lokal. Deksametason merupakan obat yang memiliki efek anti inflamasi dan antifibrosis yang dapat digunakan untuk memperbaiki jaringan parut yang timbul pasca operasi IBD. Penelitian ini bertujuan untuk membuat beads kalsium-alginat deksametason yang hanya dilepas pada kolon. Beads dibuat menggunakan natrium-alginat yang disambung silang dengan Ca2+ melalui metode gelasi ionik, dengan perbandingan antara natrium alginat-deksametason (3:1). Konsentrasi natrium-alginat yang digunakan sebesar 3% b/v dengan varian konsentrasi CaCl2 sebagai agen sambung silang yakni 2% (formula 1), 3% (formula 2), dan 4% (formula 3). Beads yang telah dibuat akan dikarakterisasi untuk mengetahui bentuk dan morfologi beads, distribusi ukuran partikel beads, kadar air, efisiensi proses, indeks mengembang, uji kandungan obat, efisiensi penjerapan deksametason dalam beads dan evaluasi pelepasan obat secara in vitro yang kadar deksametasonnya ditetapkan secara spektrofotometri UV-Vis. Hasilnya diperoleh bentuk beads yang hampir bulat dengan kisaran ukuran antara 630 - >800 µm. Efisiensi penjerapan terbesar diperoleh dari beads formula 1 yaitu sebesar 98,14% sedangkan setelah disalut dengan eudragit® S100 menggunakan alat fluid bed dryer diperoleh beads formula 4 dengan efisiensi penjerapan sebesar 67,78%. Beads formula 1 hanya bersifat enterik dan belum mampu menahan pelepasan zat aktif hingga di pH kolon, sedangkan beads formula 4 memiliki profil pelepasan yang lebih baik karena dapat melepas zat aktif sampai di pH kolon secara bertahap dan bertahan selama 8 jam saat di pH kolon.

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Inflammatory Bowel Disease (IBD) is a disease of inflammation in the colon, therefore this disease should be treated with targeted drug delivery systems on site-specific. Targeted delivery systems for the treatment of IBD is designed to increase the drug concentration in the local tissue. Dexamethasone is a drug having anti-inflammatory and antifibrosis effects which is used to repair scar tissue arising from postoperative IBD. This research purpose to create calcium-alginate beads dexamethasone to be released only in the colon. Beads were made ​​by using sodium-alginate and Ca2+ as crosslinker by ionic gelation method, with ratio between sodium alginate-dexamethasone (3:1). A concentration of solution sodium alginate 3 % b/v with variation concentration of crosslinker is 2% (formula 1), 3% (formula 2), and 4% (formula 3). Beads ​​will be characterized to determine the form and morphology of the beads, particle size distribution of the beads, moisture content, process efficiency, swelling ratio, drug content, encapsulation efficiency and drug release determined by spectrophotometry UV-Vis. The results obtained were spherical beads with a size range between 630 -> 800 μm with the greatest encapsulation efficiency obtained from the beads formula 1 with the amount of 98.14% and after coated with Eudragit® S100 using a fluid bed dryer apparatus, beads of formula 4 was obtained with an encapsulation efficiency of 67,78%. Beads formula 1 were only released in stomach pH and not able to hold up the release of the active substance in colonic pH, whereas beads of formula 4 releasing dexamethason gradually more than 8 hours in colonic pH, and has a better release profile for the active substance."

"Infeksi virus dengue (DENV) masih menjadi masalah kesehatan global di dunia termasuk Indonesia. Menurut data CDC, diseluruh dunia terdapat sekitar 400 juta kasus DENV dengan 40.000 jiwa setiap tahunnya. Keparahan infeksi DENV berkaitan dengan jumlah viral load yang tinggi dan badai sitokin yang disebabkan oleh inflamasi berlebih. Sampai saat ini tidak ada antivirus spesifik digunakan untuk DENV, sementara itu penggunaan obat anti inflamasi untuk DENV terbatas hanya untuk pasien dengan gejala klinis berat. Favipiravir dan Kina Sulfat telah dilaporkan sebagai drug repurposing yang dapat menghambat replikasi DENV, namun apakah kedua obat ini memiliki aktivitas anti-inflamasi yang disebabkan oleh infeksi DENV belum dikaji lebih lanjut. Aktivitas antivirus favipiravir dan kina sulfat dianalisis melalui nilai IC50 dan CC50 terhadap DENV serotipe-1 (DENV-1) pada sel Vero. Ekspresi relatif sitokin TNF-a, IL-6, IL-10 dan faktor transkripsi NFkB dianalisis dari PBMC donor sehat yang diinfeksikan DENV-1 dengan pemberian Favipiravir atau Kina Sulfat. Hasil penelitian menunjukkan IC50 dan CC50 untuk Favipiravir sebesar 2,72 ug/mL dan 156,78 ug/mL dengan nilai SI 58, sementara IC50 dan CC50 Kina Sulfat sebesar 14,97 ug/mL dan 85,2 ug/mL dengan nilai SI 5,69. Favipiravir dan Kina Sulfat mampu menurunkan ekspresi IL-6 dan IL-10, namun menginduksi ekspresi TNF-a dan faktor transkripsi NFkB pada dua skema uji infeksi DENV-1 dengan atau tanpa antibodi. Dari penelitian ini dapat disimpulkan bahwa Favipirafir memiliki aktivitas antivirus dengue yang lebih baik dibandingkan Kina Sulfat sementara peranan Favipiravir dan Kina Sulfat sebagai anti-inflamasi infeksi DENV masih memerlukan studi lebih lanjut.

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Dengue virus (DENV) infection is still a global health problem in the world, including Indonesia. According to CDC data, worldwide there are around 400 million DENV cases with 40,000 deaths each year. The severity of DENV infection is related to the high viral load and cytokine storm caused by excessive inflammation. Until now there is no specific antiviral used for DENV, meanwhile the use of anti-inflammatory drugs for DENV is limited to patients with severe clinical symptoms. Favipiravir and Quinine Sulfate have been reported as repurposing drugs that can inhibit DENV replication, but whether these two drugs have anti-inflammatory activity caused by DENV infection has not been studied further. The antiviral activity of Favipiravir and Quinine Sulfate was analyzed through IC50 and CC50 values against DENV serotype-1 (DENV-1) on Vero cells. The relative expression of cytokines TNF-a, IL-6, IL-10 and the transcription factor NFkB was analyzed from PBMCs of healthy donors infected with DENV-1 with the addition of Favipiravir or Quinine Sulfate. The results showed that the IC50 and CC50 for Favipiravir were 2,72 ug/mL and 156,78 ug/mL with an SI value of 58, while the IC50 and CC50 of Quinine Sulfate were 14,97 ug/mL and 85,2 ug/mL with an SI value 5,69. Favipiravir and Quinine Sulfate were able to reduce the expression of IL-6 and IL-10, but induced the expression of TNF-a and the transcription factor NFkB in two DENV-1 infection test schemes with or without ADE. From this study it can be concluded that Favipiravir has better dengue antiviral activity than Quinine Sulfate, while the role of Favipiravir and Quinine Sulfate as an anti-inflammatory for DENV infections still requires further study. From this study, it can be concluded that Favipiravir has better dengue antiviral activity than Quinine Sulfate while the role of Favipiravir and Quinine Sulfate as anti-inflammatory of DENV infection still requires further study."

"ABSTRAKObat anti-inflamasi nonsteroid (OAINS) nonselektif banyak digunakan oleh lansia. OAINS nonselektif oral memiliki efek samping terhadap gastrointestinal baik lokal maupun sistemik. Oleh karena itu, diperlukan rute untuk menghantarkan OAINS nonselektif yang nyaman dan efek samping yang minimal. Salah satunya rute alternatif yaitu penghantaran melalui kulit yang disebut rute transdermal. Stratum korneum menjadi tantangan utama dalam rute transdermal. Hal ini dapat dibantu dengan adanya peningkat penetrasi agar jumlah obat dapat mencapai efek terapeutiknya. Peningkat penetrasi sintesis menyebabkan berbagai masalah. Terpen, minyak atsiri, dan asam lemak dapat diperoleh dari alam. Minyak atsiri daun zodia (Evodia suaveolens) memiliki kandungan terpen yaitu linalool, alfa-pinen, dan limonen. Tinjauan ini membahas mengenai hubungan antara OAINS nonselektif dengan sistem penghantaran transdermal, pengaruh peningkat penetrasi dari alam terhadap OAINS nonselektif, serta potensi minyak atsiri daun zodia sebagai peningkat penetrasi pada OAINS nonselektif. Sistem penghantaran transdermal dapat mengurangi efek samping lokal yang terdapat pada gastrointestinal, selain itu sistem transdermal nyaman dan mudah digunakan. Peningkat penetrasi dapat menjadi alternatif untuk peningkat penetrasi sintesis OAINS nonselektif. Dari beberapa penelitian menunjukkan bahwa peningkat penetrasi dari alam mampu meningkatkan penetrasi obat melalui kulit. Kandungan minyak atsiri daun zodia mengandung linalool, alfa-pinen, dan limonen yang dapat berpotensi untuk menjadi peningkat penetrasi OAINS nonselektif. Untuk memperbaiki dari penelitian-penelitian sebelumnya, maka disarankan penelitian dilengkapi dengan membandingkan pengaruh dari kontrol, peningkat penetrasi sintesis (sebagai standar), serta peningkat penetrasi uji; uji kompatibilitas; penggunaan membran hewan (tikus/kelinci) pada uji in vitro; serta uji mekanisme kerja dari peningkat penetrasi

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ABSTRACT

Non-selective anti-inflammatory drugs (NSAIDs) are widely used by the elderly. Oral non-selective NSAIDs have side effects on both local and systemic gastrointestinal. Therefore, a route is needed to deliver convenient non-selective NSAIDs and minimal side effects. One alternative route is delivery through the skin called the transdermal route. The stratum corneum is the main challenge on the transdermal route. This can be helped by increasing penetration so that the amount of drug can reach its therapeutic effect. Synthesis penetration enhancers causes various problems. The terpenes, essensial oil, and fatty acid can be obtained from nature. Zodia (Evodia suaveolens) contain terpenes namely linalool, alpha-pinene, and limonene. This review discusses the relationship between non-selective NSAIDs and transdermal delivery systems, the effect of penetration enhancers from nature on non-selective NSAIDs, and the potential of Zodia as penetration enhancers in non-selective NSAIDs. The transdermal delivery system can reduce the local side effects in the gastrointestinal, besides that the transdermal system is comfortable and easy to use. Penetration enhancers can be an alternative to synthesis penetration enhancers nonselective NSAIDs. Several studies shown that natural penetration enhancers can increase drug penetration through the skin. The zodia leaf oil contains linalool, alpha-pinene, and limonene which can be potential to increase penetration of non-selective NSAIDs. To improve from previous studies, it is recommended that research should be completed by comparing the effects of controls, synthetic penetration enhancers (as a standard), and penetration enhancer test; compatibility test; use of animal membranes (mice/rabbits) for in vitro tests; and the mechanism action of penetration enhancers testing.

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