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Abstrak :
Pemberian bromelain secara oral dapat menurunkan bioaktivitasnya setelah kontak dengan asam lambung. Oleh karena itu, Bromelain dimuat ke dalam mikrosfer berbasis alginat (Alg) dan/atau pektin (Pek) untuk menghindari degradasi dan pelepasannya segera di usus. Bromelain kasar dimurnikan dengan presipitasi amonium sulfat dan proses dialisis. Mikrosfer dikarakterisasi meliputi analisis fisik, analisis FTIR, dan analisis DSC. Fraksi dialisis bromelain memiliki aktivitas spesifik 67,93 U/mg. Fraksi tersebut dienkapsulasi dalam beads Alg, Pek, dan AP dengan kisaran efisiensi enkapsulasi sekitar 82,70–91,39%. Mikrosfer Pek dan AP19 yang dimuat bromelain pada akhirnya dipilih untuk dipelajari kemampuan pelepasan in vitro berdasarkan sifat pembengkakan dan efisiensi enkapsulasi. Mikrosfer AP19 termuat bromelain memiliki pelepasan yang lebih rendah dari mikrosfer Pek termuat bromelain di medium disolusi asam dan buffer fosfat. Pelepasan kumulatif bromelain terenkapsulasi pada AP19 adalah 9,99 dan 87,81% masing-masing dalam 0,1 N HCl dan media penyangga fosfat pH 6,8. Model kinetika mikrosfer Pec dan AP termuat bromelain keduanya mengikuti orde nol dan mekanisme pelepasannya merupakan non-Fickian atau kombinasi dari difusi dan erosi. Aktivitas antiplatelet in vitro alikuot disolusi (20,51 dan 18,48%) lebih rendah dibandingkan fraksi dialisisnya (56,04%). Data penelitian in vitro ini menunjukkan potensi AP yang menjanjikan sebagai pembawa untuk pemberian bromelain secara oral sebagai agen antiplatelet. ......Oral administration of bromelain can decrease its bioactivity once it makes contact with stomach acid. Bromelain was therefore loaded into alginate (Alg) and/or pectin (Pec) beads to control its release into the intestines and avoid degradation. Crude bromelain was purified by ammonium sulphate precipitation and the dialysis process. The beads were characterized using physical analysis, FTIR analysis, and DSC analysis. The dialysis fraction of bromelain has a specific activity of 67.93 U/mg. That fraction was encapsulated in Alg, Pec, and AP beads with range of encapsulation efficiency around 82.70−91.39%. Bromelain-loaded Pec and AP19 beads were chosen to study in an in vitro release based on their swelling properties and encapsulation efficiency. Bromelain-loaded AP19 beads have lower release than bromelain-loaded Pec beads in the acid and phosphate buffer dissolution medium. The cumulative releases of AP19 are 9.99 and 87.81% in 0.1 N HCl and phosphate buffer medium, respectively. Bromelain-loaded Pec and AP beads both follow the zero orders kinetics model and the dissolution mechanism of the beads is non-Fickian with a combination of diffusion and erosion. The in vitro antiplatelet activity of dissolution aliquots (20.51 and 18.48%) is lower than its dialysis fraction (56.04%). This in vitro research data shows promising potency for AP as a carrier for oral administration of bromelain as an antiplatelet agent.

Abstrak :
Bromelain yang diisolasi dari nanas (Ananas comosus [L.] Merr) dapat menjadi agen fitoterapi yang sangat baik untuk pengobatan penyakit kardiovaskular karena dapat menghambat agregasi platelet. Namun jika digunakan secara oral, bromelain dapat dengan mudah terdegradasi dalam lingkungan pH asam. Ketidakstabilan dalam kondisi tertentu akan menurunkan aktivitas farmakologisnya dan menurunkan manfaatnya bagi kesehatan. Oleh karena itu, bromelain perlu dienkapsulasi dalam matriks seperti nanosfer alginat-karboksimetil selulosa (CMC) melalui metode gelasi ionik menggunakan ion kalsium sebagai agen pengikat silang. Formula nanosfer dievaluasi rasio swelling, ukuran partikel, dan efisiensi enkapsulasinya. Karakterisasi juga dilakukan dengan menggunakan spektrofotometer infra merah (FTIR) dan mikroskop elektron (SEM). Hasil penelitian menunjukkan bahwa formula nanosfer terbaik (611,05 ± 0,35 nm) memiliki rasio swelling sebesar 177,27% dan 2119,17% pada pH 1,2 dan pH 7,4. Uji efisiensi enkapsulasi menunjukkan bahwa nanosfer Alginate-CMC dapat mengenkapsulasi bromelain sebesar 32,2%. Pelepasan bromelain dari nanosfer alginat-CMC diamati masing-masing 14,09% dan 31,14% di lingkungan lambung dan usus buatan setelah 8 jam. Bromelain dalam nanosfer alginat-CMC mempertahankan identitasnya seperti yang diamati dalam studi FTIR. Bromelain yang dienkapsulasi memiliki aktivitas proteolitik hingga 0,60 U/mL dan aktivitas antiplatelet sebesar 73,95%. Dari penelitian tersebut, dapat disimpulkan bahwa nanosfer alginat-CMC berhasil melindungi bromelain dari lingkungan asam di lambung dan memiliki karakteristik lepas lambat di lingkungan usus buatan. Hasil ini juga menunjukkan bahwa nanosfer alginat-CMC bisa menjadi sistem pengiriman yang menjanjikan untuk pengiriman enzim ......Bromelain isolated from pineapple (Ananas comosus [L.] Merr) can be an excellent phytotherapeutic agent for cardiovascular treatment as it can inhibit platelet aggregation. However, if it is used orally, it can be easily degraded in the acidic pH environment due to enzymes secreted during the digestion process. Its instability under a certain condition will reduce its pharmacological activity and as a result, will reduce its health benefit. Therefore, bromelain needs to be encapsulated in a matrix such as alginate-carboxymethyl cellulose (CMC) nanospheres by ionic gelation method using calcium ion as a crosslinking agent. The alginate-CMC nanospheres were evaluated for their swelling ratio, particle size, and drug encapsulation efficiency. Characterization was also carried out using fourier transform infrared spectrophotometer (FTIR) and scanning electron microscope. The results showed that the best nanosphere (611.05±0,35 nm) has swelling ratios of 177.27% and 2119.17% at pH 1.2 and pH 7.4, respectively. The encapsulation test revealed that the Alginate-CMC nanospheres can encapsulate the bromelain with encapsulation efficiency of 32.2%. The release of bromelain from the nanospheres was observed 14.09% and 31.14% respectively in the artificial gastric and intestinal environment after 8 hours. Bromelain in the nanospheres retains its identity after nanospheres formation as observed in FTIR studies. The encapsulated bromelain has a proteolitic activity up to 0.60 U/mL and antiplatelet activity of 73.95%. From these studies, it can be concluded that the alginate-CMC nanospheres can successfully protect bromelain from the acidic environment in the stomach and have slow-release characteristics. These results also suggest that alginate-CMC nanospheres could be a promising delivery system for enzyme delivery

Abstrak :
ABSTRAK
Penelitian ini bertujuan untuk mengisolasi dan memurnikan enzim bromelain dari bonggol nanas (Ananas comosus [L] Merr.) disertai pengujian aktivitasnya sebagai agen antiplatelet. Tahap pemurnian dimulai dari isolasi, fraksinasi bertingkat menggunakan etanol, kromatografi penukar ion dengan DEAE-Selulosa, dan kromatografi filtrasi gel dengan Sephadex G-50. Tiap tahap pemurnian menghasilkan peningkatan aktivitas spesifik pada fraksi enzim, mulai dari ekstrak kasar berturut-turut sebesar 0,0052 Unit/mg; 4,6480 Unit/mg; 9,0306 Unit/mg; dan 11,8421 Unit/mg. Fraksi enzim yang telah melewati tahap kromatografi penukar ion dan filtrasi gel menunjukkan tingkat kemurnian tertinggi, yaitu 2277 kali dibanding ekstrak kasarnya. Hasil uji aktivitas antiplatelet terhadap seluruh fraksi enzim membuktikan bahwa bromelain berpengaruh pada proses agregasi platelet. Fraksi enzim hasil pemurnian pun menunjukkan aktivitas terbesar sebagai agen antiplatelet, yaitu memberikan nilai persentase agregasi platelet sebesar 64,04% dan nilai persentase inhibisi sebesar 31,25%. Uji stabilitas enzim menunjukkan bahwa enzim bromelain dari bonggol nanas mengalami penurunan aktivitas proteolitik sebesar 0,2315 Unit/mL per hari selama proses penyimpanan, dan dapat mengalami inaktivasi pada pemanasan suhu 80°C.

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ABSTRAK
This study aimed to isolate and purify the bromelain enzyme from pineapple core (Ananas comosus [L] Merr.), accompanied by testing that activity as a antiplatelet agents. Purification stages starting from the isolation, fractionation storied using ethanol, ion exchange chromatography with DEAE-Cellulose and gel filtration chromatography with Sephadex G-50. Each stages of purification succeed increasing value of specific activity in an enzyme fraction, start from crude extract enzyme, respectively: 0.0052 Unit/mg; 4.6480 Unit/mg; 9.0306 Unit/mg; and 11.8421 Unit/mg. Enzyme fractions have passed the stage of ion chromatography and gel filtration show the highest level of purify (2277 fold compared to the crude extract). The results of antiplatelet activity on all factions proved that the enzyme bromelain giving effect on platelet aggregation process. The fraction was purified also show greatest activity as an antiplatelet agent, with the percentage of platelet aggregation values of 64.04% and a percentage inhibition value of 31.25%. Enzyme stability test showed that the enzyme bromelain from pineapple core decreased proteolytic activity of 0.2315 units / mL per day during the storage process, and can be inactivated on heating temperature of 80°C.

Abstrak :
Penelitian ini bertujuan untuk mengisolasi dan memurnikan enzim bromelain dari bonggol nanas (Ananas comosus) dengan metode pengendapan fraksionasi menggunakan garam ammonium sulfat, diikuti dengan dialisis dan kromatografi kolom gel filtrasi. Fraksi termurni diuji aktifitas antiplatelet dan ditentukan nilai IC50. Tahap ekstraksi menghasilkan enzim kasar dengan aktifitas spesifik 0.0059 U/mg. Tahap fraksionasi pengendapan, menghasilkan fraksi enzim dengan aktifitas spesifik tertinggi pada fraksi 50 ? 80% (ke 3) yaitu sebesar 8.2243 U/mg. Fraksi 3 setelah didialisis menghasil aktifitas spesifik sebesar 8.3118 U/mg. Proses kromatografi menggunakan Sephadex G-50 menghasil fraksi enzim dengan nilai aktifitas spesifik sebesar 8.5177 U/mg pada fraksi pertama (Kr 1). Fraksi Kr 1 diuji aktifitas spesifiknya dengan metode Born dimodifikasi dan menghasilkan persen aggregasi sebesar 70.59% dan persen inhibisi sebesar 24.34%. Nilai IC50 diperoleh sebesar 57.4040 mL/mL PRP.

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This study aim to isolate and purify bromelain enzyme from pineapple core (Ananas Comosus) through fractional precipitation by ammonium sulfate, followed by dialysis and column chromatography gel filtration. The purest enzyme fraction is then measured it?s antiplatelet activity and IC50. Crude extract obtain through extraction gives 0.0059 U/mg specific activity. Fraction 3 from fractional precipitation gives the highest specific activity with 8.2243 U/mg and range from 50% to 80%. After dialysis, specific activity increase to 8.3118 U/mg and increased again through chromatography process to 8.5177 U/mg on fraction Kr 1. Antiplatelet activity of Kr 1 is then tested, and has 70.59 % aggregation, 24.34% inhibition and an IC50 value of 57.4040 mL/mL PRP.

Abstrak :
Pendahuluan: Jumlah pasien Sindrom Koroner Akut SKA semakin meningkat dari tahun ketahun. Ticagrelor merupakan penghambat P2Y12 dengan onset cepat dan efekhambatan platelet lebih besar dibandingkan klopidogrel, namun memiliki masalahmeningkatnya efek samping perdarahan mayor, efek samping lain, dan biaya yanglebih mahal. Penelitian ini bertujuan melakukan evaluasi efektifitas, keamanan,dan cost effectiveness analysis ticagrelor dibandingkan klopidogrel add on aspirinpada pasien SKA sejak tahun 2014-2016 di RSUPN Cipto Mangunkusumo. Metode:Penelitian ini menggunakan design kohort retrospektif. Rekam medis dari pasienSKA yang pertama kali didiagnosa dan diterapi dengan klopidogrel dan pasienSKA yang pertama kali didiagnosa dan diterapi dengan ticagrelor dimasukkankedalam kriteria inklusi. Outcome efektivitas adalah insiden major adversecardiovascular events MACE yang dapat dicegah dalam 3, 6, 9, dan 12 bulan.Outcome safety adalah insiden efek samping yang timbul dalam 3 bulan.Outcomebiaya dinilai dengan cost effectiveness analysis CEA . Data untuk CEA disajikandalam bentuk incremental cost effectiveness ratio ICER . Untuk menilaiketidakpastian data uncertainty digunakan analisa sensitivitas satu arah. Hasil:Rekam medis dari 123 pasien klopidogrel-aspirin dan 57 pasien ticagrelor-aspirinberhasil dievaluasi. Trend pemakaian ticagrelor semakin meningkat sejak tahun2014 sampai dengan 2016, sedangkan klopidogrel semakin menurun. Outcomeefektivitas adalah MACE yang dapat dicegah dalam 3 bulan. Dalam 3 bulanMACE terjadi pada 15.8 pasien di kelompok ticagrelor dan 31.7 pasien dikelompok klopidogrel RR; 0,498, 95 CI; 0,259 ndash;0,957, P = 0,039 . Tidak adaperbedaan signifikan pada bulan ke 6,9, dan 12. Ticagrelor memiliki efek sampingperdarahan mayor melena lebih tinggi dibanding klopidogrel 5,3 vs 1,62 , P= 0,681 , terutama pada pasien geriatri. ICER = Rp 279.438,87., denganpengertian diperlukan tambahan biaya Rp 279.438,87., untuk setiap insidenMACE yang dapat dihindari dalam 3 bulan jika digunakan ticagrelor sebagaiDAPT. ICER tersebut dianggap cost effective karena berada dibawah 1 GDP Gross Domestic Product Indonesia tahun 2016, yaitu 3603 Rp 49.000.800. Kesimpulan: Ticagrelor-aspirin lebih efektif dan lebih cost-effective dalam mencegah MACEdalam 3 bulan dibandingkan klopidogrel-aspirin pada pasien SKA. Masihdiperlukan penelitian prospektif lanjutan dengan jumlah besar terutama padapasien geriatri dengan SKA.

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Introduction The enormous number of acute coronary syndrome ACS cases make it importantto evaluate the economic burden of this illness. Ticagrelor is a P2Y12 inhibitorwith pronounced platelet inhibition effect and more rapid onset compared toclopidogrel, with disadvantages of higher price and major bleeding adverseeffects. This study aimed to evaluate effectiveness, safety, and cost effectivenessanalysis of dual antiplatelet aspirin ticagrelor compared with aspirin clopidogrelat ACS patients in Cipto Mangunkusumo Hospital during 2014 2016 Methods This is a retrospective cohort study from data records of ACS patient treated inCipto Mangunkusumo Hospital between 2014 2016 period. ACS patientsdiagnosed and treated for the first time with aspirin clopidogrel and patientsdiagnosed and treated for the first time with aspirin ticagrelor were included.Effectiveness outcome were the occurence of major adverse cardiovascular events MACE successfully avoided within 3, 6, 9, and 12 months of antiplatelettreatment. Safety outcome were the insidence of adverse drug reactions within 3months. Cost outcome were determined with cost effectiveness analysis CEA .Data for CEA calculation were presented as Incremental Cost Effectiveness Ratio ICER . One way sensitivity analysis were performed to evaluate data uncertainty. Results A total of 123 data records of ACS patients treated with aspirin clopidogrel and57 with aspirin ticagrelor were evaluated. Trend for antiplatelet prescriptionshowed that ticagrelor prescription increased since 2014 until 2016, whileclopidogrel decreased. Within the first three months, the MACE rate was 15.8 inticagrelor group and 31.7 in clopidogrel group RR 0,498, 95 CI 0,259 ndash 0,957, P 0,039 . There were no significant differences of MACE betweengroups after 6, 9, and 12 months treatment. Ticagrelor had unsignificant majorbleeding melena higher than clopidogrel 5,3 vs 1,62 , P 0,681, especiallyin geriatric patients. ICER value was IDR 279.438,87, indicating additional costneeded for every MACE incidence successfully avoided within 3 month if aspirinticagrelorwas used. ICER under 1 Indonesian GDP Gross Domestic Product in2016 3603, equal to IDR 49.000.800 is considered cost effective. Conclusions Ticagrelor aspirin is a clinically superior and cost effective option for MACEprevention among ACS patients especially during the first three monthsantiplatelet treatment. Further prospective rearch with higher number especially ingeriatric patients with ACS is still needed.

Abstrak :
Trombus adalah proses pembekuan darah yang terjadi di area pembuluh darah atau ruang jantung dan berfungsi mencegah terjadinya pendarahan. Jumlah trombus yang berlebih dalam darah menyebabkan terjadinya penyumbatan pembuluh darah sehingga dapat menimbulkan angina (nyeri dada) dan stroke. Bromelain dari bonggol nanas (Ananas comosus [L.] Merr), hasil pemurnian parsial dengan aktivitas spesifik 124,38 U/mg memiliki aktivitas inhibisi terhadap agregasi platelet sebesar 86,48%. Di sisi lain, bromelain sangat mudah terdegradasi pada cairan lambung sehingga aktivitas dan kadar enzim tersebut dapat menurun. Untuk mengatasi hal ini, bromelain dienkapsulasi ke dalam nanosfer alginat-HPMC terikat silang ion CaCl2 dengan teknik in situ loading. Nanosfer alginat-HPMC dengan nisbah 1:1 dan 1:2 terpilih sebagai penyalut bromelain hasil isolasi berdasarkan hasil optimasi rasio swelling dan efisiensi enkapsulasi. Kemudian, ke dua nanosfer tersebut dikarakterisasi berupa ukuran partikel dan morfologinya. Nanosfer dengan komposisi alginat-HPMC (1:1) memiliki ukuran 543,7±4,24 nm dan menghasilkan morfologi nanosfer yang permukaannya cukup halus dengan sedikit berpori. Sedangkan, nanosfer dengan komposisi alginat-HPMC (1:2) berukuran 515,3±26,73 nm dan memiliki permukaan nanosfer yang kasar, adanya lekukan serta lubang pada permukaannya. Evaluasi profil rilis bromelain tersalut nanosfer alginat-HPMC secara in vitro pada medium asam selama 3 jam menunjukkan bahwa nanosfer dengan komposisi alginat-HPMC 1:1 memiliki persen rilis bromelain yang lebih rendah dibandingkan dengan komposisi alginat-HPMC 1:2. Bromelain yang telah terenkap ke dalam nanosfer masih memiliki aktivitas proteolitik (1,55 U/mL) dan inhibisi agregasi platelet sebesar 71,24%. ......Thrombus is blood congealment process (platelet) occurred in area of vein and is useful for preventing of bleeding occurrence. The considerable amount of thrombus in blood leads to blocked arteries and angina pectoris. The partial purification of bromelain originated from pineapple core (Ananas comosus [L.] Merr) with the specific activity of 124,38 U/mg had inhibition activity to the platelet aggregation of 86,48%. On the other hand, the proteolytic activity of bromelain was relatively stable in the first 4 hours. However, the proteolytic activity significantly decreased in the next 4 hours due to the influence of gastric fluid (pH 1.2). To overcome the problem, bromelain must be encapsulated into alginate-HPMC nanospheres cross-linked by CaCl2 ion. Based on the optimization result of the swelling index and the entrapment efficiency, the nanospheres with the composition of alginate-HPMC 1:1 and 1:2 were the optimal formula and selected to encapsulate bromelain and be characterized by PSA and SEM. Alginate-HPMC nanospheres (1:1) had a particle size of 543,7±4.2 nm. The morphology of nanospheres was almost spherical and had a smooth surface. Moreover, the particle size of alginate-HPMC nanospheres (1:2) was 515,3±26.7 nm and the SEM micrograph showed the spherical nanospheres with slightly rough surface. Furthermore, the in vitro-release profile of bromelain loaded alginate-HPMC nanospheres in the acidic condition along 3 hours demonstrated that the release percentage of bromelain from alginate-HPMC nanaospheres with the composition of 1:1 was lower than the composition of 1:2. Moreover, the encapsulated bromelain in nanospheres with the proteolytic activity of 1,55 U/mL was still able to inhibit platelet aggregation of 71,24 %.

Abstrak :
[Konsumsi obat-obatan anti agregasi platelet (antiplatelet) seperti clopidogrel yang digunakan untuk menurunkan agregasi platelet dapat mencegah terjadinya trombosis. Namun, konsumsi obat-obatan antiplatelet sintetik seringkali memberikan efek samping bagi tubuh. Daun Tanjung (Mimusops elengi L.) dapat dimanfaatkan sebagai sumber antiplatelet alami dan murah karena mengandung senyawa katekin. Ekstraksi senyawa katekin dari daun Tanjung menggunakan metode refluks dengan pelarut air pada lima variasi waktu (15 menit, 30 menit, 45 menit, 60 menit, 75 menit) menunjukkan bahwa waktu ekstraksi 75 menit menghasilkan kandungan katekin tertinggi, yakni sebesar 452,39 ppm. Hasil analisis ekstrak menggunakan FTIR didapatkan gugus-gugus senyawa yang umumnya terkandung dalam senyawa katekin yaitu fenol, aromatik, serta eter. Efek agregasi antiplatelet dari ekstrak daun Tanjung kemudian diukur menggunakan waktu pendarahan pada mencit galur Deutsche Democratic Yokohama. Ekstrak diberikan secara oral selama 8 hari, dengan pengukuran waktu pendarahan dilakukan pada hari pertama dan hari kesembilan. Kelompok pengujian bioaktivitas antiplatelet adalah kelompok kontrol negatif, kelompok kontrol positif (clopidogrel 0,033 mg/30 gram berat mencit), serta tiga kelompok dosis; TE1 (0,0198 mg/30 gram berat mencit), TE2 (0,0396 mg/30 gram berat mencit), dan TE3 (0,0793 mg/30 gram berat mencit). Pengujian dilakukan dengan cara melukai ekor mencit untuk melihat waktu pendarahan yang dialami mencit sebelum dan sesudah pemberian ekstrak. Setelah mendapatkan peningkatan waktu pendarahan, data dianalisis menggunakan analisis uji varian (Anova) yang dilanjutkan dengan pengujian LSD menggunakan aplikasi SPPS V.16. Hasil dari peningkatan waktu pendarahan menunjukkan bahwa kelompok dosis TE3 dengan dosis 0,0793 mg/30 gram berat mencit memberikan waktu pendarahan sebesar 132.77 + 32.52% yang sebanding dengan kelompok kontrol positif sebesar 110.45 + 13.66%.

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Consumption of anti platelet aggregation (antiplatelet) drugs such as clopidogrel which is used to lower platelet aggregation can be used to prevent thrombosis. However, the consumption of synthetic antiplatelet drugs frequently give side effects to the body. Tanjung (Mimusops elengi L.) leaves can be used as a natural and inexpensive source of antiplatelet compounds that contain catechins. Extraction of catechin compounds from Tanjung?s leaves using reflux system and water as its solvent with five variations of the time (15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes) showed that the extraction time of 75 minutes produces the highest catechin content, which amounted to 452.39 ppm. FTIR analysis results obtained extracts using groups of compounds that are generally contained in catechin compounds of phenols, aromatic, and ether. Antiplatelet aggregation effect of Tanjung leaves extract then measured using bleeding time on DDY strain mice. Extracts is administered orally for 8 days, with bleeding time measurements made on the first day and the ninth day. The antiplatelet activity groups test was negative control group, positive control group (0.033 mg clopidogrel/30 gram weight of mice), and three dose groups; TE1 (0.0198 mg/30 g mouse weight), TE2 (0.0396 mg/30 gram weight of mice), and TE3 (0.0793 mg/30 g mouse weight). Tests conducted by wounding mice to see that the bleeding time of mice before and after administration of the extract. After getting an increase in bleeding time, data were analyzed with SPP V.16 application for analysis of variance test (ANOVA) followed by LSD test. The result of the increase in bleeding time suggests that TE3 dose group with a dose of 0.0793 mg/30 gram weight of the mice gave bleeding time of 132.77 + 32.52% which is comparable to the positive control group amounted to 110.45 + 13.66%., Consumption of anti platelet aggregation (antiplatelet) drugs such as clopidogrel which is used to lower platelet aggregation can be used to prevent thrombosis. However, the consumption of synthetic antiplatelet drugs frequently give side effects to the body. Tanjung (Mimusops elengi L.) leaves can be used as a natural and inexpensive source of antiplatelet compounds that contain catechins. Extraction of catechin compounds from Tanjung’s leaves using reflux system and water as its solvent with five variations of the time (15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes) showed that the extraction time of 75 minutes produces the highest catechin content, which amounted to 452.39 ppm. FTIR analysis results obtained extracts using groups of compounds that are generally contained in catechin compounds of phenols, aromatic, and ether. Antiplatelet aggregation effect of Tanjung leaves extract then measured using bleeding time on DDY strain mice. Extracts is administered orally for 8 days, with bleeding time measurements made on the first day and the ninth day. The antiplatelet activity groups test was negative control group, positive control group (0.033 mg clopidogrel/30 gram weight of mice), and three dose groups; TE1 (0.0198 mg/30 g mouse weight), TE2 (0.0396 mg/30 gram weight of mice), and TE3 (0.0793 mg/30 g mouse weight). Tests conducted by wounding mice to see that the bleeding time of mice before and after administration of the extract. After getting an increase in bleeding time, data were analyzed with SPP V.16 application for analysis of variance test (ANOVA) followed by LSD test. The result of the increase in bleeding time suggests that TE3 dose group with a dose of 0.0793 mg/30 gram weight of the mice gave bleeding time of 132.77 + 32.52% which is comparable to the positive control group amounted to 110.45 + 13.66%.]

Abstrak :
Penyakit kardiovaskular merupakan penyakit tidak menular penyebab kematian paling banyak setiap tahunnya. Salah satu gangguan kardiovaskular adalah sindrom koroner akut. Pasien dengan kondisi ini umumnya diberikan terapi antiplatelet. Bagian penting dalam proses aktivasi platelet adalah interaksi ADP dengan reseptor P2Y₁₂. Inhibitor P2Y₁₂ yang tersedia mempunyai efek samping yang tidak diharapkan, sehingga pengembangan obat dengan tujuan mendapatkan antiplatelet baru yang lebih optimal masih perlu dilakukan. Penemuan obat baru secara in silico berbasis fragmen memiliki banyak keuntungan dan cerita sukses. Pada penelitian ini, metode tersebut diterapkan dengan tujuan memperoleh struktur senyawa rancangan yang berpotensi sebagai inhibitor P2Y₁₂; memprediksi profil farmakokinetika, kemudahan sintesis, dan toksisitasnya; dan mengetahui interaksi yang terjadi antara senyawa rancangan dengan P2Y₁₂. Fragmen diperoleh dari basis data ZINC, ditapiskan terhadap parameter Rule of Three dan heavy atoms, dan ditambatkan terhadap P2Y₁₂. Penggabungan fragmen (metode linking) kemudian dilakukan setelah menganalisis interaksi fragmen dengan residu asam amino pada makromolekul. Senyawa rancangan hasil penggabungan fragmen diprediksi drug-likeness, aksesibilitas sintesis, ADME, dan toksisitasnya, serta dianalisis interaksinya dengan makromolekul. Penelitian ini menghasilkan 7 senyawa yang diprediksi memiliki nilai aksesibilitas sintesis berkisar antara 4,77 – 5,61, memiliki kriteria drug-likeness dan ADME yang baik, dan tidak bersifat toksik. Senyawa rancangan menunjukkan adanya interaksi dengan residu penting pada P2Y₁₂ yaitu residu Tyr105, Asn191, dan Lys280. Dari hasil penelitian ini, dapat disimpulkan bahwa metode in silico berbasis fragmen berhasil dilakukan untuk memperoleh kandidat inhibitor P2Y₁₂ baru.

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......Cardiovascular disease is a non-infectious disease causing the highest deaths every year. One of the cardiovascular disorders is acute coronary syndrome. Patients with this condition are generally given antiplatelet therapy. An important part of the platelet activation process is the interaction of ADP with P2Y₁₂ receptors. The commercially available P2Y₁₂ inhibitors have unexpected side effects, so the development of drug with the aim of getting more optimal antiplatelet agents remains to be done. The discovery of new drugs using an in silico fragment-based drug design has many advantages and success stories. In this study the method was applied with the aims of obtaining the new design of compound's structure which has the potential as a P2Y₁₂ inhibitor; predicting their pharmacokinetic profile, synthetic accessibility, toxicity; and knowing the interactions between the compounds and P2Y₁₂. Fragments were obtained from the ZINC database, screened on the Rule of Three and heavy atoms parameters, and docked against P2Y₁₂. Fragment linking was then performed after analyzing the interaction of fragments with amino acid residues of the macromolecule. The newly design compounds were then analyzed for their drug-likeness, accessibility of synthesis, ADME, and toxicity, and their interactions with the macromolecule. This study produced seven newly designed compounds that are predicted to have synthetic accessibility scores ranging from 4.77 to 5.61, have good drug-likeness and ADME criteria, and not toxic. Each compound showed interactions with important residues in P2Y₁₂ which are the Tyr105, Asn191 and Lys280 residues. It can be concluded that the fragment-based drug design was successfully carried out to obtain new P2Y₁₂ inhibitor candidates.

Abstrak :
Bromelain merupakan kelompok enzim protease yang terus dikembangkan untuk dimanfaatkan dalam bidang medis sebagai agen antiplatelet, antiinflamasi, antioksidan, dan antikanker. Oleh sebab itu, diperlukan bentuk sediaan enzim terkontrol yang dapat mempertahankan aktivitas enzim dalam lambung sehingga dapat meningkatkan absorbsi saat mencapai usus. Penelitian ini bertujuan untuk mempertahankan aktivitas antiplatelet bromelain hasil isolasi bonggol buah nanas dengan mengenkapsulasinya pada kitosan terikat silang glutaraldehid. Bromelin yang diisolasi dimurnikan melalui fraksinasi dengan garam amonium sulfat dan dialisis. Aktivitas spesifik dari tiap fraksi menunjukkan adanya peningkatan, dimulai dari enzim kasar (71,10 U/mg), fraksi ammonium sulfat(151,70 U/mg) dan dialisis (226,8 U/mg). Hasil dialisis selanjutnya dienkapsulasi secara post loading dalam mikrosfer kitosan terikat silang glutaraldehid 2,5% (v/v), dengan derajat ikat silang sebesar 94,87% dan rasio swelling sebesar 41,45% pada pH 1,2; 20,97% pada pH 7,4; dan efisiensi sebesar 84,75%. Hasil uji disolusi menunjukan tingkat pelepasan bromelain yang relatif lebih kecil di cairan lambung artifisial (13,43%) dibandingkan lingkungan pH usus (60,52%). Aktivitas proteolitik dari bromelain dapat dipertahankan hingga mencapai 0,35 U/mL pada lingkungan pH usus artifisial.

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Bromelain is a group of protease enzymes that continue to be developed to be used in the medical field as an antiplatelet agent, anti-inflammatory, antioxidant, and anticancer. Therefore, a controlled enzyme dosage form is needed that can maintain enzyme activity in the stomach so that it can increase absorption when it reaches the intestine. The aim of this study was to maintain the antiplatelet bromelain activity resulting from pineapple hump isolation by encapsulating it with glutaraldehyde cross-linked chitosan. Isolated bromelin was purified by fractionation with ammonium sulfate salt and dialysis. Specific activities of each fraction showed an increase, starting from crude enzymes (71.10 U/mg), ammonium sulfate fraction (151.70 U/mg) and dialysis (226.8 U/mg). The dialysis results were then encapsulated post loading in 2.5% (v/v) glutaraldehyde crosslinked chitosan microspheres, with crosslinking degrees of 94.87% and swelling ratio of 41.45% at pH 1.2; 20.79% at pH 7.4; and efficiency of 84.75%. The dissolution test results showed a relatively smaller release rate of bromelain in artificial gastric fluid (13.43%) compared to the intestinal pH environment (60.52%). The proteolytic activity of bromelain can be maintained up to 0.35 U/mL in an artificial intestinal pH environment.