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"Kanker payudara menempati urutan pertama banyaknya kejadian kanker pada wanita. Kebutuhan obat antikanker payudara yang mampu menghambat dan mematikan pertumbuhan sel kanker payudara tanpa mempengaruhi sel normal sangat penting. Secara empiris tanaman sisik naga digunakan sebagai obat kanker payudara dan kanker kolon. Ekstrak daun sisik naga mempunyai sifat sitotoksik terhadap MCF-7 dengan IC50 sebesar 83,63 µg/mL. Kandungan kimia sisik naga yang kemungkinan aktif sitotoksik adalah flavonoid, saponin, steroid, tanin dan terpenoid. Flavonoid, saponin dan tanin larut dalam pelarut polar sedangkan terpenoid dan aglikon saponin larut dalam pelarut organik non polar. Penelitian ini bertujuan mencari aktivitas sitotoksik senyawa hasil isolasi tanaman sisik naga terhadap sel kanker payudara (MCF-7 dan t47D) dan kanker kolon (WiDr) dibandingkan sel normal (Vero). Pengamatan mekanisme kematian sel diamati dengan pengecatan double stanning etidium bromida-akridin orange, % ekspresi p53 dan caspase 3, serta FTIC annexin v-propidium iodida. Ekstraksi kandungan bioaktif sitotoksik menggunakan pelarut n-heksan, diklorometana dan metanol kemudian dilanjutkan fraksinasi dan isolasi menggunakan kromatografi kolom dengan fase diam silika gel 60 dan fase gerak n-heksan, etil asetat dan metanol. Identifikasi struktur dilakukan terhadap senyawa hasil isolasi terpilih yang paling sitotoksik. Hasil penelitian diperoleh ekstrak diklorometana, fraksi II ekstrak diklorometana dan senyawa I2 hasil isolasi fraksi II ekstrak diklorometana tanaman sisik naga paling toksik terhadap sel MCF-7, t47D, WiDr dan non toksik pada sel Vero. Pemberian senyawa I2 konsentrasi IC50 terhadap sel MCF-7, t47D, dan WiDr menyebabkan peningkatan kematian sel, % ekspresi p53, % ekspresi caspase 3 dan jumlah sel mati karena apoptosis tetapi tidak menimbulkan efek pada sel Vero. Hasil identifikasi spektrum IR, 1H-NMR, 13C-NMR dan MS senyawa I2 adalah β-sitosterol (C29H50O). Penapisan in silico nampak β-sitosterol berikatan dengan CDK2 dengan sisi aktif pada Leu83 akibatnya fase S dipersingkat kembali menuju G1 dan terjadi apoptosis.

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Breast cancer is the first rank in the occurrence of cancer in women. Therefore, breast cancer drugs that inhibit cell growth and kill breast cancer cells selectively without affecting the normal cells are very important. Sisik naga was empirically used as medicine for breast and colon cancer. Sisik naga leaf extract was revealed to be cytotoxic against MCF-7 with an IC50 of 83.63 µg/ mL. Sisik naga chemical constituents that have cytotoxicity are flavonoid, saponin, steroid, tannin and terpenoid. Flavonoid, saponin and tannin are the soluble in polar solvent, while terpenoid and saponin aglycone are soluble in non polar organic solvent.

This study aims to find the cytotoxic activity of isolated compounds from sisik naga against breast cancer (MCF-7 and t47D) and colon cancer (WiDr) compared to normal (Vero) cells. Observation of the mechanism of cell death was observed by ethidium bromide-acridine orange double stanning, p53 and caspase 3 expression, and FTIC annexin v-propidium iodide stanning. Cytotoxic bioactive were extracted using hexane, dichloromethane and methanol solvent respectively, followed by fractionation and isolation using column chromatography with silica gel 60 as stationary phase and n-hexane, ethyl acetate and methanol as mobile phase. Identification of the isolated compounds structure with most cytotoxicity was done.

The results showed that dichloromethane extract, fractions II of dichloromethane extract and I2 compounds isolated from fraction II dichloromethane extracts of sisik naga were most cytotoxic to MCF-7, t47D, and WiDr, while non cytotoxic to Vero cells. Exposure to compound I2 at IC50 concentration on MCF-7, t47D, and WiDr caused increased cell death, p53 and caspase 3 expression, and increased of dead cell due to apoptosis, but showed no effect on Vero cell. Identification of IR, 1H-NMR, 13C-NMR spectrum and MS spectrum of I2 compound showed that the compound were β-sitosterol (C29H50O). The in silico screening showed that β-sitosterol appeared to bind on the active site of CDK2 at Leu83, which cause acceleration from S phase to G1 phase and apoptosis."

"Industri farmasi memiliki berbagai macam data seperti corrective and preventive action (CAPA), continuous improvement (CONIM), dan energi yang dihasilkan dalam jumlah besar dari setiap departemen. Data yang diperoleh akan diproses dan dibutuhkan oleh departemen terkait untuk mengambil keputusan serta mendapatkan informasi misalnya melihat aktual dan target yang harus tercapai. Penulisan tugas khusus ini dilakukan untuk mempermudah pengambilan keputusan oleh user melalui visualisasi data menggunakan dashboard google data studio di PT Finusolprima Farma Internasional. Penulisan tugas khusus praktek kerja dilakukan dengan membuat dashboard google data studio di departemen Manufacturing System and Technology Development (MSTD) PT Finusolprima Farma Internasional. Pada pengerjaannya, sumber data akan diambil melalui spreadsheet dan ditampilkan ke dalam bentuk grafik garis, batang, serta lingkaran yang disesuaikan dengan kebutuhan agar informasi dapat disampaikan dengan jelas secara visual.

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The pharmaceutical industry has a variety of data such as Corrective and Preventive Action (CAPA), Continuous Improvement (CONIM), and the energy produced in large quantities of each department. The data obtained will be processed and needed by the relevant departments to make decisions and get information such as seeing the actual and targets that must be achieved. Writing this special task is carried out to facilitate decision making by the user through data visualization using the Google Data Studio Dashboard at PT Finusolprima Farma International. Writing special work practices is done by creating a Google Data Studio dashboard at the Department of Manufacturing System and Technology Development (MSTD) of PT Finusolprima Farma Internasional. In the process, the data source will be taken from spreadsheet and displayed in the form of line graphs, rods, and circles that are tailored to the needs so that information can be conveyed clearly visually."

"Arginase (L-arginine ureahydrolase) adalah enzim yang berperan dalam siklusurea. Arginase juga memainkan peran penting dalam produksi nitrat oksida (NO).Gangguan keseimbangan NO merupakan kontributor terjadinya gangguan fungsiendotel pembuluh darah. Senyawa fenol dan flavonoid diketahui mempunyaiaktivitas penghambatan arginase. Genus Sterculia kaya dengan senyawa fenol danflavonoid. Penelitian ini bertujuan untuk mendapatkan senyawa dari tanaman genusSterculia yang mempunyai aktivitas penghambatan arginase. Penelitian diawalidengan skrining dari 5 tanaman genus Sterculia yaitu: S. macrophylla, S. comosa,S.parkinsonii, S.rubiginosa, S.stipulata. Bagian yang digunakan adalah daun dankayu. Ekstrak diuji aktivitas inhibitor enzim arginase dan antioksidan denganmetode DPPH dan FRAP. Ekstrak yang aktif adalah ekstrak metanol kayu Sterculiacomosa dan ekstrak metanol kayu Sterculia macrophylla. Ekstrak aktif dipisahkandengan kromatografi kolom vakum menjadi fraksi. Tiap fraksi di uji aktivitasinhibitor enzim arginase dan antioksidan dengan metode FRAP dan DPPH. Fraksidilanjutkan diisolasi menggunakan kromatografi kolom dan Kromatografi LapisTipis Preparatif sampai didapatkan isolat. Hasil isolat diidentifikasi dengan FTIR,1H-NMR,13C-NMR, HSQC, HMQC, HMBC, LCMSMS. Sterculia comosa (kayucomosa/KC) didapatkan isolat KC4.4.6 asam (-)-2-(E)-kafeoil-D-gliserat, danKC4.4.5.1 adalah asam trans-isoferulat, yang merupakan turunan sinamat. Sterculiamacrophylla (kayu macrophylla/KM) diperoleh senyawa senyawa KM3.9.1merupakan 3β-5α,6α-epoksi-3-hidroksi-7-megastigmen-9-on. Senyawa KM3.5.Mmerupakan asam pikolinat, dan Senyawa KM-1 merupakan campuran β-sitosteroldan stigmasterol. Hasil uji aktivitas inhibitor enzim arginase diperoleh nilai IC50untuk 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 isolatKM3.9.1:92,60 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: 15,79FeEAC (Mol/g) KM-1: 11,89 FeEAC (Mol/g), kontrol positif kuersetin: 1201,61FeEAC (Mol/g). Isolat KM3.9.1 (3β-5α,6α-epoksi-3-hidroksi-7-megastigmen-9-on) merupakan senyawa yang mempunyai aktivitas sebagai inhibitor enzim yangpaling baik, sedangkan aktivitas antioksidan yang paling baik adalah isolatKC4.4.6/asam ()-2-(E)-kafeoil-D-gliseratArginase (L-arginine urea-hydrolase) is an enzyme that plays a role in the ureacycle. 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 bloodvessels. Phenol and flavonoid compounds are known to have arginase inhibitoryactivity. The genus Sterculia contains rich of phenol compounds and flavonoids.This study aims to obtain compounds from the genus Sterculia which have arginaseinhibitory activity. The study began with the screening of five plants of Sterculiagenus: S. macrophylla, S. comosa, S.parkinsonii, S.rubiginosa, S.stipulata. Theparts used are leaves and wood. The extract tested for the activity of arginaseinhibitory activity and antioxidant by DPPH and FRAP methods. The activeextracts were methanol extract of Sterculia comosa wood and methanol extract ofSterculia macrophylla wood. The active extract was separated by vacuum columnchromatography into fractions. Each fraction tested for the activity of arginaseinhibitory and antioxidant by the FRAP and DPPH methods. The fraction isolatedusing column chromatography and Preparative Thin Layer Chromatography untilisolates obtained. The isolates identified with FTIR, 1H-NMR,13C-NMR, HSQC,HMQC, HMBC, LCMSMS. Sterculia comosa (comosa woods/KC) obtainedisolates KC4.4.6/(-)-2-(E)-caffeoyl-D-glyceric acid., KC4.4.5.1 trans-isoferrulicacid, which are cinnamic. Sterculia macrophylla (comosa woods/KC) obtainedcompound: 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 andstigmasterol. The results of arginase enzyme inhibitor activity obtained IC50 valuesfor 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: 88,08μg/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 wascompound that have the best activity as enzyme inhibitor, while the best antioxidantactivity was KC4.4.6/()-2-(E)-caffeoyl-D-glyceric acid."

"ABSTRAKTanaman Garcinia latissima Miq. yang tumbuh di Pulau Seram Maluku dan Papua dan dibudidayakan di Kebun Raya Bogor kemungkinan mempunyai potensi sebagai antimikroba. Tujuan dari penelitian ini untuk mendapatkan isolat senyawa aktif dari fraksi aktif sebagai antibakteri atau antifungi dan mendapatkan struktur senyawa aktif dari tanaman G. latissima Miq. Bahan tanaman kulit buah, kulit batang, dan daun Garcinia latissima Miq. masing-masing dimaserasi secara bertingkat dengan menggunakan tiga macam pelarut n-heksana, etil asetat, dan metanol sehingga diperoleh sembilan ekstrak. Uji antimikroba 9 ekstrak ini dilakukan terhadap dua bakteri gram positif Staphylococcus aureus dan Bacillus subtilis , dua bakteri gram negatif Pseudomonas aeruginosa dan Escherichia coli dan dua jamur Candida albicans dan Trichophyton mentagrophytes dengan menggunakan uji zona hambat. Ekstrak yang memberikan zona hambat, dilakukan uji zona hambat kembali dengan menggunakan 2 ekstrak dalam DMSO. Ekstrak yang memberikan zona hambat pada konsentrasi 2 dilakukan uji konsentrasi hambat minimal KHM menggunakan metode dilusi dan kemudian difraksinasi menggunakan kromatografi kolom. Fraksi-fraksi yang diperoleh diuji zona hambat dan penetapan nilai KHM secara mikrodilusi. Fraksi yang memberikan penghambatan terhadap bakteri kemudian diuji secara bioautografi sehingga dapat diketahui ada tidaknya komponen dari fraksi yang dapat memberikan zona hambat. Fraksi yang mempunyai KHM 2.500 ppm atau kurang dan yang mempunyai bobot fraksi yang memungkinkan kemudian dilakukan isolasi dengan menggunakan kromatografi kolom, kromatografi lapis tipis preparatif KLTP , dan rekristalisasi. Isolat yang diperoleh diidentifikasi menggunakan spektrometri UV-Vis, FTIR, LCMS Liquid Chromatography Mass Spectrofotometry , spektrometri 1HNMR, 13CNMR, HMQC, dan HMBC. Hasil penelitian menunjukkan bahwa ekstrak etil asetat kulit buah dan ekstrak etil asetat kulit batang pada konsentrasi 2 memberikan zona hambat terhadap B. subtilis dan P. aeruginosa. Ekstrak metanol kulit buah 2 dan ekstrak metanol kulit batang 2 memberikan zona hambat terhadap B. subtilis dan S. aureus. Ekstrak metanol kulit buah 2 juga memberikan zona hambat terhadap P. aeruginosa. Ekstrak etil asetat daun dan ekstrak metanol daun pada konsentrasi 2 memberikan zona hambat terhadap B. subtilis. Dari hasil isolasi fraksi yang mempunyai KHM le; 2.500 ppm diperoleh empat senyawa yang baru pertama kali diisolasi dari G. latissima yaitu 6-deoksijakareubin dari fraksi C ekstrak etil asetat kulit buah G. latissima Miq. , senyawa friedilin dari fraksi A ekstrak etil asetat daun , senyawa robustaflavon dari fraksi D ekstrak etil asetat daun , dan senyawa amentoflavon dari fraksi B dan fraksi C ekstrak metanol daun . Hasil uji KHM 6-deoksijakareubin terhadap B. subtilis 156,25 ppm lebih aktif dari fraksi C ekstrak etil asetat kulit buah 1.250 ppm.

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ABSTRACTGarcinia latissima Miq. which grows on the island of Seram Maluku and Papua and cultivated in the Bogor Botanical Gardens may have potential as an antimicrobial. The purpose of this study was to obtain isolates of active compounds from the active fractions as antibacterial or antifungal and to obtain the structure of the active compound of the G. latissima Miq plant. Each plant material fruits, stembark, and leaves were macerated succesively by using n-hexane, ethyl acetate, and methanol subsequently obtaining 9 extracts. Antimicrobial tests of 9 extracts were performed on two Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis , two Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli and two fungi Candida albicans and Trichophyton mentagrophytes using inhibitory zone tests. Extracts that provide inhibition zone, retard zone test conducted using 2 extract in DMSO. Extracts that gave the inhibition zone at 2 concentration were tested for minimum inhibitory concentrations MIC using the dilution method and then fractionated using column chromatography. The fractions were tested inhibit zone and stipulation of MIC values ?? ??by microdilution. Fractions that gave inhibition to the bacteria were then tested by performing bioautography assay to determine which component of the fraction that able to inhibit bacteria growth. A fraction having MIC of 2500 ppm or less and having a feasible fractional weight is then isolated by column chromatography, preparative thin layer chromatography Prep-TLC , and recrystallization. The isolates obtained were identified using UV-Vis spectrophotometry, FTIR, LCMS Liquid Chromatography Mass Spectrophotometry , 1H-NMR spectrophotometry, 13C-NMR, HMQC, and HMBC. The results showed that the fruits ethyl acetate extract and the stembark ethyl acetate extract at 2 concentration gave inhibition zone against B. subtilis and P. aeruginosa. The fruits methanol extract 2 and stembark methanol extract 2 gave inhibition zone against B. subtilis and S. aureus. The fruits methanol extract 2 also provided inhibitory zone against P. aeruginosa. The leaves ethyl acetate extract and the leaves methanol extract at 2 concentration gave inhibition zone against B. subtilis. The isolation result from fractions having MIC le; 2,500 ppm obtained four compounds which were first isolated from G. latissima, 6-deoxijacareubin from fraction C of fruit ethyl acetate extract , friedelin from fraction A of leaves ethyl acetate extract , robustaflavone from fraction D of leaves ethyl acetate extract , and amentoflavone from fraction B and fraction C of leaves methanolic extract . The MIC of 6-deoxijacareubin against B. subtilis was 156.25 ppm more active than fraction C of fruits ethyl acetate extract of 1250 ppm ."

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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.

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"Research through a metabolomics approach is carried out withoutisolating a single active compound responsible for an activity. Empirically the root, stem, and leaf preparations of Rhinachantus nasutus (L.) Kurz have long been used in traditional medicine such as the treatment of diabetes, eczema, pulmonary tuberculosis, herpes, hepatitis, and hypertension. This dissertation aims to evaluate compounds that have antioxidant and antidiabetic activity through inhibition of alpha-glucosidase activity of plant R. Nasutus metabolomics and molecular tethering based liquid chromatography very high performance mass spectrometry/mass spectrometry (KCKST SM/SM). The stages of research carried out include: (1) Extraction of leaves, flowers, and bark using 70% ethanol with ultrasonic wave-assisted extraction method. (2) Fractionation of selected extracts using centrifugation partition chromatography (PPP). (3) Testing of antidiabetic activity through the mechanism of alpha-glucosidase inhibition of selected extracts and their PPP fractions in vitro. (4) Testing of antioxidant activity by 1,1-diphenyl-2-picrylhydrazil (DPPH) method; ferric reducing antioxidant power (FRAP); cupric ion reducing antioxidant capacity (CUPRAC) in vitro against extracts and PPP fractions whose alpha-glucosidase inhibitory activity is very active and/or active. (5) Determination of metabolite profiles using KCKST SM/SM Q-Orbitrap on PPP fractions whose alpha-glucosidase inhibitory activity is very active and/or active. (6) Chemometric analysis with multivariate data analysis using SIMCA software against metabolite area area data and bioactivity data. (7) Verification of compounds that contribute significantly as inhibitors of alpha-glucosidase activity resulting from metabolomics by molecular tethering. This study obtained 10 active compounds in the inhibition of alpha-glucosidase in the KPS fraction of R. nasutus, namely compounds (5) bis(2-ethylhexyl) amines, (6) choline, (7) leu gly, (8) N-methyltanolamine phosphate, (11) N-methyldioctylamine, (14) dodesiltrimethethlammonium, (15) austalida J, (17) DL-β-leucine, (22) cemilicoisoflavone B, and (26) licoflavone B. In addition, 6 compounds (compounds 5, 8, 11, 14, 15, and 22) contributed significantly as alpha-glucosidase inhibitors as well as very strong antioxidants with the FRAP method and 3 compounds (compounds 5, 11, and 15) with the CRAPC method.

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In the metabolomics approach, research is done without isolating any active compounds that cause activity. Empirically, preparations of the roots, stems, and leaves of Rhinachantus nasutus (L.) Kurz have long been used in traditional medicine for such purposes as the treatment of diabetes, eczema, pulmonary tuberculosis, herpes, hepatitis, and hypertension. This dissertation aims to evaluate compounds with antioxidant and anti-diabetic activity by inhibiting the alpha-glucosidase activity of the plant R. nasutus using a metabolomics approach and molecular docking based on ultra-high performance liquid chromatography mass spectrometry/mass spectrometry (UHPL MS/MS). The stages of the research included: (1) extraction of leaves, flowers, and stem bark using 70% ethanol using an ultrasound-assisted extraction (UAE) method. (2) Fractionation of selected extracts using centrifugation partition chromatography (CPC). (3) In vitro testing of antidiabetic activity through the mechanism of alpha-glucosidase inhibition of selected extracts and their CPC fractions. (4) Testing the antioxidant activity with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) in vitro against extracts and CPC fractions with highly active, active, or slightly active alpha-glucosidase inhibitory activity. (5) Determination of metabolite profiles using KCKST SM/SM Q-Orbitrap on CPC fractions with highly active or slightly active alpha-glucosidase inhibitory activity. (6) Chemometric analysis in the form of multivariate data analysis using SIMCA software on metabolite area data and bioactivity data. (7) Verification of compounds that contribute significantly as inhibitors of alpha-glucosidase activity in metabolomics by molecular docking.This study obtained 10 active compounds in alpha-glucosidase inhibition in the R. nasutus CPC fraction, namely compounds (5) bis(2-ethylhexyl) amine, (6) choline, (7) leugly, (8) N-methylethanolamine phosphate, (11) N-methyldioctylamine, (14) dodecyltrimethylammonium, (15) austalide J, (17) DL-β-Leucine, (22) semilicoisoflavone B, and (26) licoflavone B. In addition, it was also found that six compounds (compounds 5, 8, 11, 14, 15, and 22) significantly contributed as alpha-glucosidase inhibitors as well as very strong antioxidants with the FRAP method and three compounds (compounds 5, 11, and 15) with the CUPRAC method."

"Diabetes mellitus tipe II adalah penyakit gangguan metabolik yang gejalanya adalah hiperglikemia atau tingkat glukosa darah yang meningkat, yang disebabkan oleh rusaknya fungsi insulin baik dalam sekresi, kerja, atau keduanya. Penyakit ini adalah penyakit menahun yang bisa menyebabkan berbagai komplikasi. Salah satu pendekatan untuk mengobati penyakit diabetes mellitus tipe II adalah dengan memperlambat penyerapan glukosa melalui penghambatan α-glukosidase. Enzim α-glukosidase akan mengkatalisasi hidrolisis gula kompleks, termasuk karbohidrat, menjadi glukosa yang bisa diserap dalam usus. Dengan demikian penghambatan α-glukosidase akan menghambat pembentukan glukosa yang bisa diserap usus, yang kemudian akan memperlambat kenaikan tingkat glukosa darah. Banyaknya penderita diabetes mellitus tipe II mendorong usaha untuk mencari senyawa aktif penghambat α-glukosidase baru dari bahan alam, yang diharapkan mempunyai efikasi yang lebih baik atau lebih mudah diekstrak atau disintesis daripada yang ada sekarang. Penelitian ini bertujuan untuk mencari senyawa aktif penghambat α-glukosidase dari bahan alam yang ada di Indonesia, khususnya dari tanaman Artabotrys sp. Ada 4 jenis tanaman Artabotrys sp. yang diteliti keaktifan ekstrak etanolnya terhadap penghambatan α-glukosidase: Artabotrys hexapetalus (daun dan kulit batang), Artabotrys suaveolens (daun dan kulit batang), Artabotrys blumei (batang dan ranting), dan Artabotrys sumatranus (daun dan ranting). Hasil pengetesan menggunakan bioassay menunjukkan bahwa ekstrak etanol yang memiliki aktivitas penghambatan α-glukosidase terkuat adalah dari daun A. sumatranus, disusul berturut-turut oleh ranting A. sumatranus, daun A. suaveolens, kulit batang A. hexapetalus, kulit batang A. suaveolens, batang A. blumei, ranting A. blumei, dan terakhir daun A. hexapetalus. Skrining juga dilakukan dengan pengetesan bioassay DPPH (2,2-diphenyl-1-picrylhydrazyl) dan FRAP (ferric ion reducing antioxidant power) untuk mengetahui aktivitas antioksidan ekstrak etanol Artabotrys sp. yang ada, dan didapatkan bahwa secara umum aktivitas penghambatan α-glukosidase mempunyai relasi positif dengan aktivitas antioksidan. Analisis tes total fenolik, total flavonoid, tes aktivitas antioksidan (DPPH dan FRAP), dan tes aktivitas penghambatan α-glukosidase; serta relasi antara tes-tes tersebut, menghasilkan prediksi golongan senyawa aktif penghambat α-glukosidase pada ekstrak Artabotrys sp. dan relasinya terhadap aktivitas antioksidan. Prediksi tahap skrining ini secara umum dikonfirmasi oleh hasil penambatan molekuler pada senyawa-senyawa yang terindentifikasi dari analisis LC-MS/MS (liquid chromatography – tandem mass spectrometry) pada ekstrak yang ada. Penelitian lalu difokuskan pada ekstrak daun A. sumatranus yang memiliki potensi yang paling tinggi dalam penghambatan α-glukosidase dan memiliki aktivitas antioksidan yang terkuat dibandingkan ekstrak Artabotrys sp. yang lain. Perbandingan antara hasil tes aktivitas antioksidan dan penghambatan α-glukosidase, serta tes total fenolik dan total flavonoid, memberikan indikasi bahwa kebanyakan senyawa penghambat α-glukosidase pada daun A. sumatranus memiliki aktivitas antioksidan, dan berasal dari golongan fenolik dan flavonoid. Teknik metabolomik tak bertarget berbasis LC-MSn dengan menggunakan analisis statistik multivariat dan machine learning lalu dipakai untuk memprediksi senyawa aktif penghambat α-glukosidase yang juga memiliki aktivitas antioksidan pada daun A. sumatranus. Data input adalah data dari 30 sampel ekstrak daun A. sumatranus dengan berbagai kombinasi pelarut etanol dan air, serta pengulangannya, dengan 80 variabel independen (fitur) berupa nilai m/z dari senyawa yang terdeteksi pada ekstrak tersebut. Variabel output (target) adalah aktivitas penghambatan α-glukosidase (target utama) dan aktivitas antioksidan (dalam bentuk penghambatan DPPH, target sampingan) yang dinyatakan dengan nilai IC50 dan 1/IC50. Pendekatan analisis statistik multivariat dilakukan dengan berbagai metode yaitu PCA (Principal Component Analysis), PLS (Partial Least Square), OPLS (Orthogonal Partial Least Square), PLS-DA (Partial Least Square – Discriminant Analysis), dan OPLS – DA (Orthogonal Partial Least Square – Discriminant Analysis). Pendekatan machine learning dilakukan secara bertingkat, dengan yang pertama membuat model prediksi keaktifan ekstrak terhadap penghambatan α-glukosidase (dilakukan dengan metode random forest yang memiliki performansi paling baik dibandingkan metode lain), yang lalu dilanjutkan dengan analisis fitur (senyawa) yang paling berpengaruh pada model prediksi keaktifan ekstrak tersebut dengan metode permutasi acak dan SHAP (Shapley additive explanations). Penggabungan hasil metode statistik multivariat dan machine learning menghasilkan prediksi sembilan senyawa aktif penghambat α-glukosidase dari daun A. sumatranus. Diantara kesembilan senyawa aktif tersebut hanya enam yang dapat teridentifikasi yaitu mangiferin, neomangiferin, norisocorydine, lirioferin, apigenin-7-O-galaktopyranosida, dan 15,16-dihydrotanshinone. Hasil penambatan molekuler menggunakan α-glukosidase dari Saccharomyces cerevisiae menunjukkan hanya mangiferin, apigenin-7-O-galaktopyranosida, dan lirioferin yang memiliki energi bebas pengikatan yang lebih negatif (lebih aktif) dibanding acarbose yang digunakan sebagai pembanding. Sedangkan penambatan molekuler menggunakan sebagian dari α-glukosidase pada usus manusia mendapatkan hanya norisocorydine saja yang lebih lemah keaktifannya dibandingkan acarbose. Analisis korelasi menunjukkan bahwa senyawa yang diprediksi aktif, termasuk yang belum teridentifikasi, mempunyai aktivitas antioksidan dan terindikasi berasal dari beberapa biosynthesis pathway. Selanjutnya isolasi senyawa aktif penghambat α-glukosidase dilakukan dengan metode fraksinasi yang dipandu dengan bioassay, diikuti dengan elusidasi strukturnya. Senyawa aktif yang didapat adalah mangiferin, yang merupakan salah satu senyawa yang diprediksi aktif dari analisis metabolomik, dengan IC50 83,72 µg/ml terhadap α-glukosidase dari Saccharomyces cerevisiae. Kontribusi dari penelitian ini adalah memperkaya wawasan kegunaan dan literatur akan A. sumatranus yang belum pernah ada publikasinya. Selain itu, penelitian ini berhasil menemukan beberapa senyawa potensial penghambat α-glukosidase yang belum pernah dipublikasikan sebelumnya, seperti apigenin-7-O-galactopyranoside, lirioferine, and norisocorydine; selain yang belum teridentifikasi. Hasil penelitian ini dapat dikembangkan selanjutnya menjadi sediaan herbal.

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Diabetes mellitus type II is a metabolic disease whose symptom is hyperglycemia or elevated blood glucose level, caused by insulin malfunctions, either in its secretion, action, or both. This disease is a chronic disease that can cause many complications. One of the diabetes mellitus treatments is delaying glucose absorption using α-glucosidase inhibition. The α-glucosidase enzyme will catalyze the hydrolysis of complex sugar, including carbohydrate, into glucose that can be absorbed in the intestine. Therefore, inhibiting α-glucosidase will inhibit the production of glucose that can be absorbed in the intestine, which will then slow down the increase of blood glucose. The large number of diabetes mellitus type II patients drives the efforts to find new active α-glucosidase inhibitor compounds from natural products, which are hoped to have better efficacies or can be more easily extracted or synthesized compared to the existing ones. This research goal was to find active α-glucosidase inhibitor compounds from natural compounds which are available in Indonesia, especially from Artabotrys sp. plants. There are 4 kinds of Artabotrys sp. plants whose ethanol extract’s activity in α-glucosidase inhibition was investigated: Artabotrys hexapetalus (leaf and stem bark), Artabotrys suaveolens (leaf and stem bark), Artabotrys blumei (stem and twig), and Artabotrys sumatranus (leaf and twig). Bioassay test results showed that ethanol extract that had the strongest α-glucosidase inhibition activity was the leaf of A. sumatranus, followed in succession by twig of A. sumatranus, leaf of A. suaveolens, stem bark of A. hexapetalus, stem bark of A. suaveolens, stem of A. blumei, twig of A. blumei, and lastly leaf of A. hexapetalus. Screening was also done by doing bioassay tests of DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric ion reducing antioxidant power) to know about the antioxidant activities of the ethanol extracts of the available Artabotrys sp., and it was found out that in general α-glucosidase inhibition activity had positive relation to antioxidant activity. Analyses of total phenolic test, total flavonoid test, antioxidant activity tests (DPPH and FRAP), and α-glucosidase inhibition activity test; as well as the relation between those tests, lead to predictions of the groups of the active α-glucosidase inhibitor compounds in the extract of Artabotrys sp. and their relations to antioxidant activity. These predictions in the screening stage were in general confirmed by the results of molecular docking of the identified compounds from LC-MS/MS (liquid chromatography – tandem mass spectrometry) analyses on the available extracts. The research was then focused on the leaf extract of A. sumatranus which had the highest potency in α-glucosidase inhibition and had the strongest antioxidant activity compared to other extracts of Artabotrys sp. Comparisons between test results of antioxidant and α-glucosidase activities, as well as total phenolic and total flavonoid, indicated that most of the α-glucosidase inhibitor compounds in the leaf of A. sumatranus had antioxidant activities, and belonged to phenolic and flavonoid groups. Untargeted metabolomic techniques based on LC-MSn by using multivariate statistical analysis and machine learning were then used to predict the active α-glucosidase inhibitor compounds which also had antioxidant activities. The input data was data from 30 samples of leaf extracts of A. sumatranus with various solvent combinations of ethanol and water, and their duplications, with 80 independent variables (features) consisting of m/z values of detected compounds in those extracts. The output variables (targets) were α-glucosidase inhibition activity (main target) and antioxidant activity (in the form DPPH inhibition, secondary target), which were represented by the value of nilai IC50 dan 1/IC50. The multivariate statiscal analysis approach was done with several methods, which were PCA (Principal Component Analysis), PLS (Partial Least Square), OPLS (Orthogonal Partial Least Square), PLS-DA (Partial Least Square – Discriminant Analysis), and OPLS – DA (Orthogonal Partial Least Square – Discriminant Analysis). The machine learning approach was done in stages, with the first one was making a prediction model of the α-glucosidase inhibition activity of the extracts (done with random forest method which had the best performance compared to other methods), and then followed by analysis of the most important features (compounds) in the extract’s activity prediction model using random permutation and SHAP (Shapley additive explanations) methods. Combining the results of multivariate statistical methods and machine learning produced a prediction of nine active α-glucosidase inhibitor compounds from the leaf of A. sumatranus. From these nine active compounds, only six could be identified which were mangiferin, neomangiferin, norisocorydine, lirioferin, apigenin-7-O-galaktopyranosida, and 15,16-dihydrotanshinone. Molecular docking using α-glucosidase from Saccharomyces cerevisiae showed only mangiferin, apigenin-7-O-galactopyranoside, and lirioferine had more negative free energy binding (more active) than acarbose, which was used as comparison. On the other hand, molecular docking using a part of α-glucosidase from humans showed only norisocorydine had weaker activity than acarbose. The correlation analyses showed that the predicted active compounds, including the unidentified ones, had antioxidant activities and were indicated to come from several biosynthesis pathways. Next, the isolation active compound as α-glucosidase inhibitor was done by using bioassay-guided fractionation, continued by structure elucidation. The isolated active compound turned out to be mangiferin, which was one the predicted compound from metabolomic analysis, with IC50 83,72 µg/ml with respect to α-glucosidase from Saccharomyces cerevisiae. The contribution of this research is to enrich and broaden the knowledge about the usefulness and literature on A. sumatranus, which had no publications before. Moreover, this research succeeded in discovering potential α-glucosidase inhibitors which were not yet published before, such as apigenin-7-O-galactopyranoside, lirioferine, and norisocorydine; besides the unidentified ones. The results of this research can be developed later on to become herbal medicine."