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SEMISINTESIS DAN KARAKTERISASI ANTIMALARIA BARU TURUNAN EURIKUMANON Hanifah Yusuf; Kurnia Fitri Jamil; Tristia Rinanda
Jurnal Kedokteran Syiah Kuala Vol 17, No 1 (2017): Volume 17 Nomor 1 April 2017
Publisher : Universitas Syiah Kuala

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Abstrak. Meluasnya penyebaran resistensi Plasmodium terhadap antimalaria merupakan permasalahan utama dalam pemberantasan malaria.Upaya cepat untuk mengatasi masalah tersebut, salah satunya melalui penemuan dan pengembangan antimalaria barudari tumbuhan obat yang secara empiris telah terbukti khasiatnya. Eurikumanon dari akar tumbuhan Eurycoma longifolia, Jack telah terbukti memiliki aktivitas antimalaria. Permasalahan dalam pengembangan eurikumanon dari bahan alam adalah biaya isolasi yang mahal, sehingga perlu usaha kreatif dan inovatif untuk mendapatkan turunannya. Semisintesis turunan eurikumanon merupakan langkah awal pengembangan eurikumanon menuju total sintesis guna memenuhi kebutuhan global. Penelitian ini menggunakan eurikumanon dari akar pasak bumi untuk semisintesis turunannya dengan menggunakan farmakofor tionil klorida, asetil klorida, asam klor asetat, asam triklor asetat dan asam trifluoro asetat. Struktur eurikumanon dan turunan hasil semisintesisditentukan secara analisis spektroskopi. Hasil ekstraksi serbuk akar pasak bumi, diperoleh ± 50 g (5%) ekstrak kental. Fraksinasi terhadap ekstrak tersebut secara kromatografi cair vakum (KCV) diperoleh fraksi terkonsentrasi eurikumanon 20 g (2%). Isolasi eurikumanon dari fraksi ini diperoleh eurikumanon 0,03%. Hasil semisintesis turunan eurikumanon diperoleh eurikumanon diklorida 60,10%, eurikumanon monoasetat55,25% , eurikumanon monoklor asetat 55,25%., eurikumanon monotriklor asetat 53,25% dan eurikumanon monotrifluoro asetat 75,65%.Kata kunci: eurikumanon, semisintesis dan turunan eurikumanon Abstract.The widespread of resistant Plasmodium to antimalarial is a mainly problem in treatment of malaria. The fast effort to overcome the problem is the discovery and development of new antimalarial from medicinal plant which is empirically proven. Eurycomanone from pasakbumi roots (Eurycoma longifolia, Jack) has been proven as antimalaria. The problem in development of eurycomanone is the high cost of isolation, therefore needed the creative and inovative effort for getting its derivatives by semisynthesis and total synthesis to fill the need of new antimalarial drugs globally. This research used isolated eurycomanone for semisynthesize its derivatives by using pharmacophore thionyl chloride, acetyl chloride, chloracetic acid, trichlor acetic acid and trifluoro acetic acid. The chemical stucture of them were determined by spectroscopic analysis. The result of extraction of pasak bumi roots is obtained ± 50 g (5%) thick extract. The fractination of this extract by vacum liquid chromatography (VLC) is obtained eurycomanone fraction ± 20 g (2%). Isolation of eurycomanone from this fraction is yielded eurycomanone ± 0,03%. Semisynthesis of eurycomanone derivatives were obtained eurycomanone dichloride 60,10%, eurycomanone monoacetic 55,25% , eurycmanone monochlor acetic 55,25%., eurycomanone monotrichlor acetic 53,25% and eurycomanonone monotrifluoro acetic 75,65%.Keywords: eurycomanone, semisynthesis and eurycomanone derivatives

Uji Toksisitas Akut Ekstrak Etanol Daun Klausena (Clausena anisata Hook.f.) Hanifah Yusuf
Jurnal Kedokteran Syiah Kuala Vol 11, No 1 (2011): Volume 11 Nomor 1 April 2011
Publisher : Universitas Syiah Kuala

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Abstrak. Daun klausena (Clausena anisata Hook.f) termasuk familia Rutaceae, telah digunakan masyarakat Sumatera Barat dan Jawa untuk menghilangkan nyeri, baik nveri kepala, nyeri gigi, rematik dan demam. Secara klinik penggunaan obat tradisional tidak diakui, bila belum terbukti secara ilmiah tentang khasiat maupun keamanannya. Karena belum adanya bukti tentang keamanannya, maka penelitian ini dilakukan untuk mengetahui dosis letalis 50 (LD 50) ekstrak etanol daun klausena pada tikus putih. Penelitian eksperimental laboratorik ini menggunakan Rancangan Acak Lengkap (n = 5) dengan hewan percobaan tikus putih (Rattus nrvergicus) jantan dan betina sehat, galur wistar, umur ± 2 bulan, dan berat badan ± 200 g. Enam kelompok tikus putih diberi ekstrak etanol daun klausena secara oral, dengan 5 tingkatan dosis (0,55 mg, 1,1 mg, 2,2 mg, 4,4 mg dan 8,8 mg/ 200 g BB). Hasil penelitian menunjukkan bahwa terdapat kematian tikus putih 3 ekor pada dosis 4,4 mg/200 g BB dan 5 ekor pada dosis 8,8 mg/200 g BB ekstrak etanol daun klausena. Hal ini menunjukkan bahwa ekstrak etanol daun klausena tidak toksik dengan nilai LD 50 = 17036,85 mg/ kg BB secara oral. Pada pemeriksaan mikroskopik terhadap organ utama kelompok hewan yang mendapatkan dosis tertinggi (8,8 mg/200 g BB) terlihat adanya perubahan berupa degenerasi sel, nekrosis dan pendarahan. Abstract. The leaves of klausena plant (Clausena anisata Hook.f), belongs to Rutaceae family has been used by the people in West Sumatera and Java to treat the pain, like headache, toothache, rheumatism and fever. The used of this medicinal plant is not recognized clinically, because it has not been tested scientifically, primary about it's pharmacological activity and safety. Because their safety has not been proven, therefore this research has been done for knowing the lethalic dose 50 (LD50) of ethanolic extract from the leaves of klausena in rats. The experimental laboratoric research has been done, using Completely Randomized Design (n = 5) and as experimental animal used male and female rats (Rattus norvegicus), wistar strain, fine, approximately 2 months age and weighed 200 g. Six groups of rats has been treated orally with the ethanolic extract from the leaves of klausena (Clausena anisata Hook.f) in five level doses (0,55 mg, 1,1 mg, 2,2 mg, 4,4 mg dan 8,8 mg/ 200 g Body Weight of rat). The result showed 3 rats at dose 4,4 mg/200 g and 5 rats at doses 8,8 mg/200 g Body Weight of rat were died. The obtained indicated the ethanolic extract from the leaves of klausena is not toxic in rats and the value of lethalic dose is 17036, 85 mg / kg Body Weight, orally. Microscopically, at the high dose on experimental animal primary organ has been found some changes, like degeneration; necroses and bleeding of cells.

Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis - A systematic review and meta-analysis Marhami Fahriani; Muhammad Ilmawan; Jonny K. Fajar; Helnida A. Maliga; Andri Frediansyah; Sri Masyeni; Hanifah Yusuf; Firzan Nainu; Francesco Rosiello; Salin Sirinam; Synat Keam; Youdiil Ophinni
Narra J Vol. 1 No. 2 (2021): August 2021
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narraj.v1i2.36

The study sought to determine the prevalence of persistent long COVID symptoms such as anxiety, depression, dizziness, chest pain, sleep difficulty, palpitations, weight loss, and hair loss among coronavirus disease 2019 (COVID-19) survivors worldwide and to discuss the potential pathogeneses. Potential studies were searched in three databases (PubMed, Scopus, and Web of Science) as of January 30, 2021. Data on study characteristics, patient characteristics during the follow-up, the number of patients with persistent long COVID symptoms and total COVID-19 survivors were collected according to PRISMA guidelines. To assess the quality of studies, the Newcastle-Ottawa scale was used. The estimated prevalence of each long COVID symptom and the association between COVID-19 severity and the occurrence of prolonged symptoms was assessed, if appropriate. The global prevalence of prolonged anxiety was 15.76% (95%CI: 6.36%, 25.15%). Chest pain persisted in 10.36% (239/3,224) of COVID-19 patients (95%CI: 4.92%, 15.80%). Prolonged depression was found in 24 of 548 COVID-19 survivors with an estimated prevalence of 4.32% (95%CI: 2.62%, 6.03%) and dizziness was presented in 4.83% (118/2,219, 95%CI: 1.50%, 8.16%) after recovery. Hair loss was complained by 527 of 2,251 recovered patients (cumulative prevalence of 24.76%, 95%CI: 19.60%, 29.91%), while weight loss was identified in 37 cases among 452 COVID-19 survivors (8.19%, 95%CI: 5.66%, 10.71%). Prolonged palpitation was experienced by 19.38% (211/1,926) survivors with 95%CI: 2.40%, 41.16%. Sleep difficulty was found in 541 of 2,622 COVID-19 survivors (17.87%, 95%CI: 7.55%, 28.20%). The association between COVID-19 severity and the occurrence of persistent long COVID symptoms was not analyzed due to the lack of data. In conclusion, persistent psychological symptoms are frequently reported among COVID-19 survivors. Follow-up studies with a longer duration and larger population are warranted to assess the extent of prolonged symptoms and the quality of life of COVID-19 survivors. Despite various potential pathogeneses that have been hypothesized, a definitive mechanism is yet to be addressed.

Global prevalence of persistent neuromuscular symptoms and the possible pathomechanisms in COVID-19 recovered individuals: A systematic review and meta-analysis Jhonny K. Fajar; Muhammad Ilmawan; Sukamto Mamada; Endang Mutiawati; Milda Husnah; Hanifah Yusuf; Firzan Nainu; Salin Sirinam; Synat Keam; Youdiil Ophinni; Francesco Rosiello; Marhami Fahriani; Sandro GV. Rosa
Narra J Vol. 1 No. 3 (2021): December 2021
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v1i3.48

This study was conducted to determine the prevalence of prolonged neuromuscular symptoms, including fatigue, anosmia, headache, myalgia, and joint pain in COVID-19 survivors hospitalized with mild, moderate, or severe infections worldwide. The search was conducted up to January 30th, 2021 using three databases (PubMed, Scopus, and Web of Science) to identify potentially eligible studies. Data on study characteristics, follow-up characteristics, and severity of COVID-19 during hospitalization were collected in accordance with PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of relevant articles. The estimated prevalence of specific prolonged neuromuscular symptoms and the association between COVID-19 severity and occurrence of prolonged neuromuscular symptoms was analyzed wherever appropriate. Database search yielded 4,050 articles and 22 articles were included for meta-analysis. The estimated prevalence of prolonged fatigue was recorded in 21.2% (95%CI: 11.9%–34.8%) of 3,730 COVID-19 survivors. Persistent anosmia was recorded in 239 of 2,600 COVID-19 survivors (9.7%, 95%CI: 6.1%–15.2%). In 84 out of 2,412 COVID-19 survivors (8.9%, 95%CI: 3.2%–22.6%), prolonged headache was observed. A total of 53 out of 1,125 COVID-19 patients (5.6%, 95%CI: 2.1%–14.2%) complained of persistent myalgia even after being discharged from the hospital. The prevalence of prolonged joint pain was in 15.4% (95%CI: 8.2%–27.2%) of subjects. Due to data scarcity on COVID-19 severity and prolonged neuromuscular symptoms, association analysis could not be conducted. Widespread concern regarding long-term impacts of COVID-19 was raised after several studies reported prolonged symptoms in COVID-19 survivors. Numerous theories have been proposed to address this concern; however, as the research on this pandemic is still ongoing, no explanation is definitive yet. Therefore, follow-up studies in COVID-19 survivors after recovery from COVID-19 are warranted to determine the pathogenesis of prolonged symptoms. PROSPERO registration: CRD42021242332.

Anticancer activity and apoptotic induction of Chromolaena odorata Linn leaves extract and fractions on hepatocellular carcinoma cell lines (HepG2) HANIFAH YUSUF; MARHAMI FAHRIANI
Jurnal Natural Volume 22 Number 1, February 2022
Publisher : Universitas Syiah Kuala

The purpose of this study is to screen and to evaluate anticancer activity and apoptosis induction of Chromolaena odorata (C. odorata) leaves extract and its fractions on HepG2 cancer cell lines. The C. odorata leaves were extracted by maceration using ethanol 80% then fractionated by using n-hexane, ethyl acetate and ethanol. MTT assay method was used to evaluate anticancer activity and flowcytometri method used to evaluate the induction of apoptosis. The phytochemical analysis and characterization of the major compound of the extract and the fractions were done by using Liquid Chromatography-Mass Spectroscopy (LCMS). The phytochemical analyis showed that the crude ethanolic extract and fractions of C. odorata leaves contains alkaloid, flavonoids, phenolic, steroids, tannin and saponin. The result of LCMS shown the major compounds of the extract and fractions are 5,7,8,3′,4′-Pentamethoxyflavonone, 1-Carboethoxy-β-carboline, 3-Methylcanthin-2, 6- dion, Canthin-6-one. In the n-hexane fraction obtained 5,7,8,3′,4′-Pentamethoxyflavonone, Methyl ophiopogonanone A and Pd-C-Ⅱ. Meanwhile, in the ethyl acetate fraction contained, 3-(3′,4′-Dihydroxybenzyl)-7-hydroxychroman-4-one, 3-(4'-Hydroxy-benzyl)-5,7-dihydroxy-6-methyl-8- methoxy-chroman-4-one, Methyl opiopogonanone A and Sinensetin. The ethanol fraction, contained the compound 3-(3′,4′-Dihydroxybenzyl)-7-hydroxychroman-4-one, 3-(4'-Hydroxy-benzyl)-5,7-dihydroxy-6-methyl-8- methoxy-chroman-4-one and Methyl opiopogonanone A. The crude ethanolic extract, n-hexane fraction, ethyl acetate and ethanol fraction extract have anticancer activities with IC50 value of 23.44 mg/mL, 84.52mg/mL; 88.51mg/mL; and 167.49 mg/mL respectively. This research suggests the crude ethanolic extract of Chromolaena odorata leaves has a potential candidate for hepatocarcinoma treatment.

ANTICANCER ACTIVITY OF ETHANOL EXTRACT OF YELLOW ROOT (Arcangelisia flava) ON HEPG2 HEPATOCELLULAR CANCER CELLS Hanifah Yusuf; Marhami Fahriani; Cut Murzalina
Jurnal Kedokteran Hewan Vol 16, No 1 (2022): March
Publisher : Universitas Syiah Kuala

This study aimed to evaluate anticancer activity and apoptosis induction of ethanolic extract of Arcalengisia flava (AF) roots on HepG2 cancer cell lines. The AF roots were extracted by maceration using ethanol 80%. MTT assay method was used to evaluate the anticancer activity and the proliferation of HepG2 cells. Flow cytometry method was used to assess the induction of HepG2 cells apoptosis. This study showed that the IC50 of AF ethanol extract against HepG2 cells was 109.14 μg/ml. With IC50 treatment, the apoptosis assay showed a significant decrease in intact cells (80.10±1.7%) and a significant increase in early apoptosis (7.9±0.7%) and late apoptosis cells of HepG2 cancer cells (4.9±0.35%) compared to control cells. Moreover, the proliferation of HepG2 cells was declined significantly in 48 and 72 hours after treatment with IC50 (77.5±5.76% and 64.3±5.37%, respectively) and 2xIC50 of the extract (75.9±1.79% and 70.5±4.27%, respectively). This research suggests that the ethanolic extract of AF roots can potentially be used for hepatocarcinoma treatment.

A CLOSE POSITIVE ASSOCIATION BETWEEN OBESITY AND BLOOD PRESSURE IN RATS Yusni Yusni; Hanifah Yusuf
Jurnal Kedokteran Hewan Vol 16, No 1 (2022): March
Publisher : Universitas Syiah Kuala

The purpose of this study was to analyze how the effect of each increase in Body Mass Index (BMI) on the increase in blood pressure (BP). The research design was a laboratory experiment with 52 non-obese and obese rats as subjects (non-obese, n=14 and obese, n=38). Rats were induced obesity using a high-fat diet for four weeks. BMI used is based on the Lee Index with obesity indicators if 300 g/cm. Data analysis using independent sample t-test, simple linear regression test, and Pearson correlation test; (p0.05). The results: BP in non-obese rats was lower than obese rats (89.00±7.38 vs 190.11±4.42; p=0.001*), BMI was positively associated with BP (p=0.001*); an increase in BMI will increase BP (p=0.001*), there is a strong correlation between BMI and BP (r=0.977; p=0.001*). The regression equation (Y = 707.42 + 2.75 X) indicates that every 1 g/cm increase in BMI will be followed by an increase in BP of 2.75 mmHg. The analysis of R-square = 0.942 shows that the accuracy of the linear equation model is 94.2%. In conclusion, BMI has a strong positive correlation with BP, an increase in BMI will increase BP; obesity induces high blood pressure in rats.

GROWTH INHIBITION AND INDUCTION OF APOPTOSIS IN MCF-7 AND T47D BREAST CANCER CELL LINES BY ETHANOL EXTRACT OF SEURAPOH (Chromolaena odorata) LEAVES Hanifah Yusuf; Reno Keumalazia Kamarlis; Yusni Yusni
Jurnal Kedokteran Hewan Vol 14, No 3 (2020): September
Publisher : Universitas Syiah Kuala

This study aims to determine the growth inhibition and apoptosis induction of MCF-7 and T47D cancer cells by ethanol extract of Chromolaena odorata leaves. A post-test with control group design was used in this study. The extract was made by maceration with 80%ethanol and the tested concentrations used were 7.80 µg/mL-500 µg/mL with standard drug doxorubicin ranged from 1.56 µg/mL-100 µg/mL.The growth inhibition was determined by the MTT colorimetry method, apoptosis induction by double staining using acridine orange-ethidiumbromide, and the existence of apoptosis was proven immunocytochemically through the expression of Bcl-2 proteins. The results showed that the growth inhibition of MCF-7 was 100.29%-28.19% and T47D was 100.37%-16.01%. The IC50 values of MCF-7 was 327.34 µg/mL and T47D was 135.16 µg/mL. The presence of apoptosis was marked by finding the morphological change of cells such as dead, necrosis, and chromatin condensation cells. This suggests that interventions with ethanol extract of Chromolaena odorata leaves can induce apoptosis that has been proven by reducing the expression of Bcl-2 proteins.

Anticancer activity and apoptotic induction of Chromolaena odorata Linn leaves extract and fractions on hepatocellular carcinoma cell lines (HepG2) HANIFAH YUSUF; MARHAMI FAHRIANI
Jurnal Natural Volume 22 Number 1, February 2022
Publisher : Universitas Syiah Kuala

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24815/jn.v22i1.22854

The purpose of this study is to screen and to evaluate anticancer activity and apoptosis induction of Chromolaena odorata (C. odorata) leaves extract and its fractions on HepG2 cancer cell lines. The C. odorata leaves were extracted by maceration using ethanol 80% then fractionated by using n-hexane, ethyl acetate and ethanol. MTT assay method was used to evaluate anticancer activity and flowcytometri method used to evaluate the induction of apoptosis. The phytochemical analysis and characterization of the major compound of the extract and the fractions were done by using Liquid Chromatography-Mass Spectroscopy (LCMS). The phytochemical analyis showed that the crude ethanolic extract and fractions of C. odorata leaves contains alkaloid, flavonoids, phenolic, steroids, tannin and saponin. The result of LCMS shown the major compounds of the extract and fractions are 5,7,8,3′,4′-Pentamethoxyflavonone, 1-Carboethoxy-β-carboline, 3-Methylcanthin-2, 6- dion, Canthin-6-one. In the n-hexane fraction obtained 5,7,8,3′,4′-Pentamethoxyflavonone, Methyl ophiopogonanone A and Pd-C-Ⅱ. Meanwhile, in the ethyl acetate fraction contained, 3-(3′,4′-Dihydroxybenzyl)-7-hydroxychroman-4-one, 3-(4'-Hydroxy-benzyl)-5,7-dihydroxy-6-methyl-8- methoxy-chroman-4-one, Methyl opiopogonanone A and Sinensetin. The ethanol fraction, contained the compound 3-(3′,4′-Dihydroxybenzyl)-7-hydroxychroman-4-one, 3-(4'-Hydroxy-benzyl)-5,7-dihydroxy-6-methyl-8- methoxy-chroman-4-one and Methyl opiopogonanone A. The crude ethanolic extract, n-hexane fraction, ethyl acetate and ethanol fraction extract have anticancer activities with IC50 value of 23.44 mg/mL, 84.52mg/mL; 88.51mg/mL; and 167.49 mg/mL respectively. This research suggests the crude ethanolic extract of Chromolaena odorata leaves has a potential candidate for hepatocarcinoma treatment.

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