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"ABSTRAKPemutihan gigi sudah menjadi kebutuhan banyak orang untuk menunjangpenampilan estetika. Pada prosedur pemutihan gigi, biasanya menggunakanbahan-bahan pemutih seperti hidrogen peroksida, karbamid peroksida, dankarbopol. Namun bahan-bahan pemutih gigi tersebut dapat menimbulkan efeksamping seperti sensitifitas gigi paska tindakan serta iritasi pada rongga mulut danmukosa saluran cerna bila tertelan. Buah alpukat, apel, mangga, nanas, dan pisangadalah jenis buah yang diketahui mengandung hidrogen peroksida. Penelitian inibertujuan untuk mengetahui efek pada jus buah alpukat, apel, mangga, nanas, danpisang dalam memutihkan gigi yang mengalami diskolorisasi ekstrinsik. Gigipremolar post-ekstraksi yang telah diskolorisasi teh dan diskolorisasi kopi diberiperlakuan jus buah selama 14 hari. Hasil uji menunjukkan bahwa terjadiperubahan rata-rata skala warna pada kelompok teh dengan perlakuan jus buahalpukat, apel, mangga, nanas, dan pisang dari skala 12 menjadi rata-rata sebesar5,4 ± 0,51; 4,4 ± 1,07; 4,9 ± 1,07; 4,5 ± 0,97 dan 4,8 ± 1,13. Sedangkan padakelompok kopi dengan perlakuan jus buah alpukat, apel, mangga, nanas, danpisang dari skala 9 menjadi rata-rata sebesar 1,6 ± 0,69; 2,2 ± 1,54; 2,2 ± 1,31; 1,5± 1,84; 1,37 ± 1,06.

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ABSTRACTTeeth whitening has become a need for many people to support the aestheticappearance. In the teeth whitening procedure, usually using bleaching ingredientssuch as hydrogen peroxide, carbamide peroxide, and carbopol. However theingredients of teeth whitening can cause side effect such as tooth sensitivity andirritation after the action in the oral cavity and gastrointestinal mucosa if ingested.Avocado, apple, mango, pineapple, and bananas are the types of fruit are knownto contain hydrogen peroxide. This study aims to determine the effect on fruitjuice avocado, apple, mango, pineapple, and banana in the teeth whiteningexperience extrinsic discoloration. Post-extraction of premolars that haddiscoloration of tea and coffee discoloration of the treated fruit juice for 14 days.The test results showed that the average changes color scale on tea grouptreatment with avocado fruit juices, apple, mango, pineapple, and banana of thescale of 12 to an average of 5.4 ± 0.51; 4.4 ± 1.07; 4.9 ± 1.07; 4.5 ± 0.97 and 4.8 ±1.13. Whereas in the coffee group treated fruit juice with avocado, apple, mango,pineapple, and banana of the scale of 9 to an average of 1.6±0.69; 2.2 ± 1.54; 2.2± 1.31, 1.5 ± 1.84; 1.37 ± 1.06."

"Kulit buah delima (Punica granatum Linn) mengandung senyawa asam elagat yang potensial sebagai SERMs alami. Penelitian bertujuan untuk mengetahui apakah pemberian fraksi air kulit buah delima (FA) bermanfaat sebagai terapi hormonal pada defisiensi estrogen, dibandingkan dengan obat standar 17- estradiol dan tamoxifen. Metode ovariektomi digunakan untuk mewakili kondisi hipoestrogen menggunakan 42 tikus betina galur Sprague Dawley usia 50 hari yang diinduksi osteoporosis selama 21 hari (kecuali sham), dibagi menjadi 7 kelompok: sham; OVX; OVX-estradiol (0,1 mg/kg BB, p.o.); OVX-tamoxifen (10 mg/kg BB p.o.); OVX-FA dengan variasi dosis 50; 100; dan 200 mg/kg BB, p.o). Perlakuan diberikan setiap hari selama 28 hari.Hasil penelitian menunjukkan bahwa dibandingkan kelompok OVX, kelompok FA dosis 200 mg/kg BB mengalami peningkatan rerata kadar hormon estradiol darah (pg/ml) dari 46,11 + 3,301 menjadi 91,78 + 18,382 (p<0,05), peningkatan rerata kadar kalsium darah (mg/dl) dari 379,38 + 55,684 menjadi 475,43 + 38,321 (p<0,05), peningkatan rerata kadar fosfor darah (mg/dl) dari 30,74 + 21,697 menjadi 74,96 + 8,413 (p<0,05) dan rerata penambahan bobot badan tikus (gram) berkurang, dari 77,28 + 22,979 menjadi 32,55 + 18,408 (p<0,05). Sedangkan rerata kadar kolesterol total darah (mg/dl) kelompok FA dosis 50 mg/kg BB mengalami penurunan (p<0,05) (79,66 + 10,936) dibandingkan kelompok OVX (102,82 + 5,761). Disimpulkan bahwa pemberian FA mampu meningkatkan kadar estradiol darah yang berefek pada penurunan kadar kolesterol total darah dan mengurangi penambahan bobot badan pada tikus ovariektomi serta berefek pada parameter yang terkait bone remodelling yaitu mampu meningkatkan kadar kalsium darah dan mempertahankan homeostatis kadar fosfor dalam darah.

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Pomegranate pericarp contain ellagic acid which potential as natural SERMs. This study aim to determine whether administration of pomegranate pericarp water fraction (FA) useful as hormonal therapy for estrogen deficiency, compare to 17-estradiol and tamoxifen, with forty-two-50-days-old female, 21 days-induced osteoporosis (except sham), assigned into 7 groups: SHAM; OVX; OVX-estradiol (0,1 mg/kgBW); OVX-tamoxifen (10 mg/kgBW); OVX-FA (50; 100 ; and 200 mg/kgBW). Treatment was given for 28 days.The results showed, compared to OVX, administration of FA 200 mg/kgBW increased blood estradiol hormones levels (pg/ml) from 46,11 + 3,301 to 91,78 + 18,382 (p<0,05), increased blood calcium levels (mg/dl) from 379,38 + 55,684 to 475,43 + 38,321 (p <0,05), increased blood phosphorus levels (mg/dl) from 30,74 + 21,697 to 74,96 + 8,413 (p <0,05) and reduced body weight gain (gr) from 77,28 + 22,979 to 32,55 + 18,408 (p<0,05). While at FA 50 mg/kgBW, blood total cholesterol levels (mg/dl) is decreased (p<0,05) (79,66 + 10,936) compare to OVX (102,82 + 5,761). Administration of FA increase blood estradiol levels, decrease blood total cholesterol levels, reduce body weight gain of ovariectomized rats, and on parameters related to bone remodeling it can increase blood calcium levels and maintain homeostatic of blood phosphorus levels."

"ABSTRAKPenelitian terdahulu menunjukkan bahwa ekstrak metanol 80% daun Cassiafistula L. serta fraksi-fraksinya berpotensi sebagai antitirosinase sehingga dapatmenghambat pembentukan melanin. Penelitian ini bertujuan untuk memperolehsediaan krim yang mengandung fraksi nonpolar, yaitu fraksi n-heksana dariekstrak etanol 96% daun trengguli, yang mempunyai aktivitas antioksidan danantitirosinase, stabil dan aman. Metode untuk menguji aktivitas antioksidanadalah metode DPPH, sedangkan untuk pengujian aktivitas antitirosinasedilakukan dengan mengukur penurunan intensitas warna yang menunjukkanpenghambatan pembentukan dopakrom dalam reaksi tirosinase-L-DOPA.Parameter adanya aktivitas ditunjukkan oleh persentase inhibisi dan nilai IC50. Ujistabilitas fisik terhadap krim dilakukan selama 12 minggu dan uji keamanankepada sukarelawan menggunakan metode single application closed patchepicutaneous test under occlusion. Hasil uji aktivitas antioksidan menunjukkanekstrak etanol 96% daun trengguli dan fraksi n-heksana memiliki nilai IC50sebesar 70,196 μg/mL dan 141,459 μg/mL secara berurutan. Pengujian aktivitasantitirosinase menunjukkan nilai IC50 ekstrak etanol 96% daun trengguli 393,264μg/mL dan nilai IC50 fraksi n-heksana 188,239 μg/mL. Konsentrasi fraksi nheksanadalam krim dibuat menjadi 3 macam, yaitu 0,1; 0,5; dan 2,5%. Hasil ujistabilitas terhadap krim selama 12 minggu menunjukkan ketiga konsentrasi krimbersifat stabil. Uji keamanan ketiga konsentrasi krim terhadap sukarelawan tidakmenimbulkan reaksi iritasi sehingga aman diaplikasikan ke kulit.

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ABSTRACTPrevious study reported that methanol 80% extract of Cassia fistula L. leaves andits fractions have potency as antityrosinase which can inhibit melanin production.This research was conducted to obtain nonpolar fraction (n-hexane fraction)-containing cream from ethanol 96% extract of Cassia fistula L. leaves, which wasconsidered potent as antioxidant and antityrosinase, stable, and safe. DPPHmethod was used to determine antioxidant activity, while antityrosinase activityassay performed by measuring the decreasing in color intensity which inhibitdopachrome formation resulted in tyrosinase-L-DOPA reaction. Parameter foridentifying activity were determined by inhibitory percentage and IC50. Physicalstability test was done for 12 weeks and safety test in human used singleapplication closed patch epicutaneous test under occlusion method. The result ofantioxidant activity test showed that ethanol 96% extract of Cassia fistula L.leaves and n-hexane fraction had IC50 values 70,196 μg/mL and 141,459 μg/mL,respectively. Antityrosinase test showed that IC50 value of ethanol 96% extract ofCassia fistula L. leaves was 393,264 μg/mL, while IC50 values of n-hexanefraction was 188,239 μg/mL. Fraction of n-hexane was formulated into cream for3 concentrations, which are 0,1; 0,5; and 2,5%. The stability test of the creams for12 weeks indicated that creams were stable. The result of safety test of creamsshowed that creams have no irritation effect so it was safe for topical applicationin human skin."

"ABSTRAKAgen pencerah kulit yang berasal dari bahan alam kini banyak diteliti karena dinilailebih aman. Salah satu tanaman yang memiliki potensi sebagai agen pencerah kulitadalah Cassia fistula L. Penelitian ini dilakukan untuk menguji secara in vitroaktivitas antioksidan dan penghambatan tirosinase oleh fraksi air daun Cassia fistulaL. serta uji manfaat fraksi tersebut dalam sediaan gel. Penetapan antioksidan denganmetode DPPH dan uji penghambatan tirosinase dengan microplate reader. Ujimanfaat dilakukan pada 33 orang wanita dengan penggunaan gel dengan konsentrasi2% selama 28 hari yag dibandingkan dengan kontrol negatif. Uji aktivitas antioksidandidapatkan hasil IC50 118,05.1 μg/ml dibandingkan dengan vitamin C dengan nilaiIC50 2,51 μg/ml. Sedangkan aktivitas inhibisi tirosinase oleh fraksi air didapatkannilai IC50 165,27 μg/ml yang dibandingkan dengan asam kojat sebagai kontrol positifdengan nilai IC50 7,12 μg/ml. Uji kinetika menunjukkan fraksi air daun trenggulimenginhibisi tirosinase secara unkompetitif. Uji manfaat dengan analisis bivariat, gelyang mengandung fraksi air daun trengguli dengan uji T-test berpasangan terbukti adapenurunan yang signifikan secara statistik didapati p 0,000 (p<0,05), dengan rata-ratapenurunan indeks melanin kulit sebesar 4,54 sampai dengan 5,03. Berdasarkan hasiltersebut dapat disimpulkan fraksi air daun trengguli memiliki kemampuan sebagaiagen pencerah kulit.

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ABSTRACTSkin-lightening agent derived from natural materials widely researched now becauseit is more secure than syntetic agent. One of the plants that have potential as a skinlightening agent is Cassia fistula L. This researches was conducted to examine the invitro antioxidant activity and inhibition of tyrosinase by a water fraction of Cassiafistula L. leaves and the efficacy test of trengguli water fraction in gel formulation.Determination of antioxidant with DPPH and tyrosinase inhibition test with amicroplate reader. Efficacy test conducted on 33 women used the gel for 28 days with2% concentration compared with negative controls. Antioxidant activity assayshowed IC50 118,05 μg/ml compared with vitamin C with IC50 value 2,51 μg/ml.Activity of tyrosinase inhibition by water fraction obtained IC50 value 165,27 μg/mlcompared with kojic acid as positive control with IC50 value of 7,12 μg/ml . Enzymekinetics assay showed that water fraction of trengguli leaves extract inhibitedtyrosinase with uncompetitive inhibition type. Efficacy test using bivariate analysis,gel formulation containing 2% water fraction of trengguli leaves with paired T-testproved there was a statistically significant decrease, p- value 0,000 ( p < 0,05 ), withan average decrease in skin melanin index of 4,54 to 5,03. Based on these results canbe concluded trengguli leaves water fraction has the ability as a skin lighteningagent ."

"ABSTRAKDiacetyl boldine merupakan bahan aktif yang berfungsi sebagai pencerah kulitmelalui antagonis reseptor α-adrenergik dan regulasi ion kalsium. Diacetylboldine tidak secara langsung berkompetisi dalam menghambat tirosinase, tetapitirosinase tetap dalam keadaan tidak aktif. Efek mencerahkan kulit juga diperolehdari asam laktat yang mengangkat sel-sel terpigmentasi pada epidermis danniasinamid yang menghambat transfer melanosom dari melanosit ke keratinosit.Kombinasi zat aktif tersebut dibuat dalam bentuk sediaan mikroemulgel.Penelitian ini bertujuan untuk memperoleh formulasi sediaan mikroemulgelsabun pembersih dan pencerah wajah yang mempunyai stabilitas yang baiksecara fisik, efektif serta aman. Evaluasi dan uji stabilitas fisik dilakukan selama 8minggu pada suhu 28°±2°C, 4°±2°C, 40°±2°C dan cycling test, dan uji in-vivo(uji manfaat dan keamanan) dan uji kesukaan (hedonik). Hasil penelitianmenunjukkan bahwa mikroemulgel berhasil dibuat dengan dengan surfaktan(Tween 80 30%, SLES 15%, kokamide DEA 5%, cocamidropil betaine 5%),kosurfaktan (gliserin 25%), fase minyak (minyak kedelai 5% dan caprylic caprictriglyceride 4%) dan fase air 16%. Mikroemulgel memiliki karakteristik berwarnakuning jernih, sifat alir newton, berukuran 1,1 nm dan stabil secara fisik padasuhu 28°±2°C, 4°±2°C, 40°±2°C. Hasil secara in-vivo menunjukkanmikroemulgel aman untuk digunakan dan menunjukkan manfaat dalammencerahkan kulit secara statistik berbeda bermakna (P < 0,05) pada formula F3.Mikroemulgel sabun pembersih dan pencerah wajah yang mengandung diacetylboldine dapat diterima dengan baik oleh konsumen

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ABSTRACTDiacetyl boldine is an active ingredient functioning as skin lightening through α -adrenergic receptor antagonists and calcium ion regulation. Diacetyl boldinecompetes indirectly to inhibits tyrosinase, but tyrosinase is stil inactive form. Skinlightening effect also derived from lactic acid which exfoliate pigmented cells inepidermis and niacinamide which inhibits melanosomes transfer frommelanocytes to keratinocytes. Combination of those active ingridients was madeinto microemulgel form. This study research aimed to get microemulgel cleansingand lightening facial soap. Formulation which have a good physical stability,effectivity, and safety. Evaluation and physical stability test performed for 8weeks at 28°±2°C, 4°±2°C, 40°±2°C and cycling test, in-vivo test (efectivity andsafety test) and likely test (hedonic). The results showed that mikroemulgelsuccessfully made of the surfactant (Tween 80 30% , SLES 15%, cocamide DEA5%, cocamidropil betaine 5%), cosurfactant (glycerin 25%), oil phase (5%soybean oil and caprylic capric triglyceride 4%) and 16% aqueous phase.Microemulgel had a clear yellow color characteristics, newton flowing properties,sized 1,1 nm and was physically stable at 28°±2°C, 4°±2°C, 40°±2°C. The resultsof the in-vivo showed that microemulgel was safe to use there also a statisticallysignificant difference in skin lightening ( P < 0.05 ) in F3 formula. Mikroemulgellightening soaps and facial cleansers containing diacetyl boldine were wellaccepted by consumers."

"Inflamasi yang tidak terkontrol menjadi penyebab kematian yang signifikan di seluruh dunia dan merupakan faktor penting dalam kasus COVID-19 yang parah. EmponEmpon (EE), merupakan jamu tradisional Indonesia secara empiris diyakini mampu menyembuhkan COVID-19 yang parah. Namun, mekanisme kerja senyawa utama dalam mengobati keparahan COVID-19 masih belum jelas. Penelitian ini bertujuan mengidentifikasi senyawa utama EE dan mekanisme molekulernya dalam mengendalikan inflamasi pada COVID-19. Senyawa EE diidentifikasi menggunakan KNApSAcK, protein/target yang terhubung senyawa dikumpulkan menggunakan database: ChemBL, GeneCard, dan Traditional Chinese Medicine Systems Pharmacology (TCMSP), sedangkan target terhubung penyakit dikumpulkan menggunakan GeneCard database. Analisis protein-protein interaction (PPI) dibangun menggunakan String, analisis Gene Ontology (GO) dan Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment menggunakan ShinyGO 0.8. Jaringan interaksi senyawa-target-pathway divisualisasikan dan dianalisis menggunakan Cytoscape 3.10. Analisis penambatan molekul menggunakan PyRx 0.98 serta analisis molecular dynamics simulation (MD) menggunakan NAMD. Diperoleh sebanyak 336 senyawa dalam EE, 28 senyawa diantaranya memenuhi kriteria penyaringan berdasarkan bobot molekul (BM): 200-500 dalton, Oral bioavailability (OB) ≥ 30%, drug-likeness (DL) ≥ 0.18, tidak menghambat CYP2D6 di hati, toksisitas ≥ III. sebanyak 578 target EE diidentifikasi terlibat dalam inflamasi dan COVID-19. Analisis GO dan KEGG mengungkap bahwa aksi farmakologi EE melalui berbagai jalur, termasuk jalur kanker, lipid dan aterosklerosis, serta COVID-19. Analisis PPI diperoleh sebanyak 6 target yang memainkan peran essensial dalam mengendalikan inflamasi dan mengobati COVID-19, yaitu: MAPK3, EGFR, AKT1, PTGS2, TNF dan IL-6. Analisis penambatan molekul menunjukkan bahwa α-amyrin, Biochanin-A, Delphinidin, Sesamin, Isorhamnetin, Guaiacin, dan Ellagic acid adalah senyawa yang mampu terikat kuat pada MAPK3, EGFR, AKT1, PTGS2, TNF dan IL-6; hasil ini diperkuat oleh analisis MD yang mengkonfirmasi bahwa interaksi antara senyawa dengan kompleks target esensialnya stabil. Temuan ini memberikan landasan teoritis mekanisme EE dalam mengendalikan inflamasi pada COVID-19, yang dapat digunakan untuk mengembangkan jamu berbasis EE

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Uncontrolled inflammation is a significant cause of death worldwide and is an essential factor in severe cases of COVID-19. Empon-Empon (EE), a traditional Indonesian herbal medicine, is empirically believed to be able to cure severe COVID-19. However, the mechanism of action of the main compound in treating the severity of COVID-19 is still unclear. This study aims to identify the main compounds of EE and their molecular mechanisms in controlling inflammation in COVID-19. EE compounds were identified using KNApSAcK, and compound-related proteins/targets were collected using ChemBL, GeneCard, and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases. In a while, disease-linked targets were collected using the GeneCard database. Protein-protein interaction (PPI) analysis was built using String, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment using ShinyGO 0.8. The compound-target-pathway interaction network was visualized and analyzed using Cytoscape 3.10. Molecular docking analysis using PyRx 0.98 and molecular dynamics simulation (MD) analysis using NAMD. A total of 336 compounds were obtained in EE, 28 of which met the screening criteria based on molecular weight (BM): 200-500 daltons, Oral bioavailability (OB) ≥ 30%, drug-likeness (DL) ≥ 0.18, does not inhibit CYP2D6 in the liver, toxicity ≥ III. A total of 578 EE targets were identified as being involved in inflammation and COVID-19. GO and KEGG analyses revealed the pharmacological actions of EE through various pathways, including cancer, lipid and atherosclerosis, and COVID-19 pathways. PPI analysis revealed six essential targets in controlling inflammation and treating COVID19, namely MAPK3, EGFR, AKT1, PTGS2, TNF, and IL-6. Molecular docking analysis showed that α-amyrin, Biochanin-A, Delphinidin, Sesamin, Isorhamnetin, Guaiacin, and Ellagic acid were compounds that were able to bind strongly to MAPK3, EGFR, AKT1, PTGS2, TNF, and IL-6; these results were confirmed by MD analysis which confirmed that the interaction between the compound and its essential target complex was stable. These findings provide a theoretical basis for the mechanism of EE in controlling inflammation in COVID-19, which can be used to develop EE-based herbal medicine."

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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."