Articles

In vivo Antiplasmodial of the Most Active Fraction and Its Compound of Kapur Leaves (Harmsiopanax aculeatus Harms) Extract Against Plasmodium berghei Turalely, Rachel; Susidarti, Ratna Asmah; Wijayanti, Mahardika Agus
Tropical Medicine Journal Vol 1, No 2 (2011): Tropical Medicine Journal
Publisher : Fakultas Kedokteran bekerjasama dengan PETRI

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Introduction : The rising of Plasmodium resistance towards chloroquine and other antimalarial drugs have encouraged to discover and develop new drugs mainly derived from natural products. Harmsiopanax aculeatus (kapur plant) has traditionally used by people of in Maluku Province to treat malaria.Objectives: The aims of this study were to identify antiplasmodial activity and its chemical constituents of the most active fraction of kapur leaves.Methods: The dried powder of Kapur leaves (1.3 kg) were extracted successively by maceration with n-hexane, ethyl acetate and methanol. After removal the solvents the hexane 15.6 g (1.2%), ethyl acetate 53.3 g (4.1%) and methanol 61.1 g (4.7%) extracts were obtained. Those extracts were assayed for their in vivo antiplasmodial activities by using 4-days suppressive test in Swiss mice infected with Plasmodium berghei, HPIA and identified the compound by GC-MS.Results: The ED50 of hexane, ethyl acetate and methanol extracts were 467.58, 2074.02 and 16.16 mg/kgBW, respectively. Fractionation of the methanol extract gave 18 combined fractions (FG1 – FG18). FG8 was the most active fraction with the IC50 HPIA of 18.22 μg/ml. Phytochemical test of this fraction using spray reagent showed the existence of essential oils, triterpenoids, and phenolic compounds. Separation of FG8using pressed chromatography gave 19 combined fractions (FG8.1-FG8.19). The fraction containing intense blue fluorescent spot (FG8.5) was further separated by PLC fourthly eluted with chloroform. Seven major components with the percentage of compotition more than 3.11% were identified as eugenol (tr = 12.692; 18.22%), isoprophyl myristate (tr = 16.333; 3.99%); bis(2-methylpropyl) phtalat (tr = 16.939; 7.15%); methyl palmitic (tr = 17.442; 3.11%); palmitic acid (tr = 17.883; 25.72%); butyl 2-methylpropyl phtalat (tr = 17.957; 9.37%) and bis(2-ethylhexyl) phtalat (tr = 23.258; 23%).Conclusion: Methanol extract of H. aculeatus was the most potential in vivo antiplasmodial activity. Combined fraction 8 which contain 7 compounds was the most active fraction.Keywords: Harmsiopanax aculeatus Harms, in vivo antiplasmodial, HPIA, PLC, GC-MS
Optimasi Sintesis Senyawa 1-(2,5-Dihidroksifenil)-(3-Piridin-2-IL) Propenon Sebagai Antiinflamasi Menggunakan Variasi Katalis NaOH Wibowo, Andy Eko; Saputra, Andy Kurniawan; Susidarti, Ratna Asmah
PHARMACY: Jurnal Farmasi Indonesia (Pharmaceutical Journal of Indonesia) Jurnal Pharmacy, Vol. 15 No. 02 Desember 2018
Publisher : Fakultas Farmasi, Universitas Muhammadiyah Purwokerto

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30595/pharmacy.v15i2.3698

Abstract

Senyawa 1-(2,5-dihidroksifenil)-(3-piridin-2-il)-propenon merupakan senyawa kalkon yang memiliki aktifitas antiinflamasi sebanding dengan ibuprofen dan aktifitas antioksidannya sangat kuat setara dengan quercetin. Senyawa ini telah disintesis menggunakan 2,5-dihidroksiasetofenon dan piridin-2-karbaldehida dengan metode radiasi microwave dan katalis K2CO3 tanpa pelarut selama 4 menit. Dalam upaya memperoleh rendemen yang lebih baik, dilakukan penelitian dengan mengganti katalis, yaitu menggunakan katalis NaOH. Penelitian dilakukan dengan mereaksikan senyawa 2,5-dihidroksiasetofenon dan piridin-2-karbaldehida dengan variasi katalis NaOH sebesar 0–0,002 mol. Senyawa disintesis menggunakan kekuatan radiasi microwave sebesar 140 watt selama 4 menit. Setelah proses sintesis maka dilakukan perhitungan rendemen senyawa 1-(2,5-dihidroksifenil)-(3-piridin-2-il)-propenon untuk mengetahui massa katalis NaOH yang optimal dalam menghasilkan rendemen terbanyak. Berdasarkan hasil yang didapat, massa katalis optimum untuk sintesis senyawa 1-(2,5-dihidroksifenil)-(3-piridin-2-il)-propenon adalah 0,0010 mol dengan rendemen sebesar 13,23%.
SynergisticCombinationofCiplukan(Physalis angulata) HerbsEthanolicExtractandDoxorubicinonT47DBreast CancerCells Armandari, Inna; Palupi, Kartika Dyah; Farida, Sofa; Hermawan, Adam; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 1, No 1 (2010)
Publisher : Indonesian Research Gateway

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Doxorubicinisoneofchemotherapeuticagentwidelyusedinbreastcancertreatment,but in high dose doxorubicin gives negative side effect, including vomit, nausea, immune suppression, and cardiac toxicity. This toxicity hopefully could be reduced by combination chemotherapy using natural herbs such as ciplukan herb. This research was conducted to explorecytotoxicactivityofsingleciplukanherbsethanolicextractanditscombinationwith doxorubicinonT47Dbreastcancercells.Cytotoxicactivityofciplukanherbsethanolicextract only and its combination with doxorubicinwere tested on T47D cells using MTT assay toobtainIC50valueandcombinationindex(CI),respectively.Singleextractshowedcytotoxic activityonT47DcellswithIC50valueofwas160*g/ml.Thus,combinationtreatmentfrom ciplukanherbsethanolicextractanddoxorubicinshowedsynergisticeffect(CI<1,0).Thiseffect wasreachedatconcentrationofciplukanherbsethanolicextract-doxorubicin80μg/ml-2nM, 80 μg/ml-4 nM, and 80 μg/ml-8 nM. This research indicated that ciplukan herbs ethanolic extractispotentialtobeappliedasco-chemotherapeuticagentinbreastcancertherapy.
Ethanolic Extract of Moringa oleifera L. Increases Sensitivity of WiDr Colon Cancer Cell Line Towards 5-Fluorouracil Nur, Kholid Alfan; Putri, Herwandhani; Cahyani, Fany Mutia; Katarina, Aulia; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 1, No 2 (2010)
Publisher : Indonesian Research Gateway

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For more than four decades, combination chemotherapy (co-chemotherapy) has been employed as a means to increase the effectiveness of chemotherapy regiments. The aim of our research is to investigate the activity of  Moringa oleifera  L. (tanaman kelor) ethanolic extract (MEE) as a co-chemotherapy agent with 5-fluorouracil (5-FU) on WiDr colon cancer cell line. Evaluation of MEE potency as a co-chemotherapy agent with 5-FU was based on cytotoxic activity based on percent cell viability via MTT  assay, and based on apoptosis observation via the double staining method using acrydin orange – ethidium bromide (AE) as the staining reagent.Cytotoxicity evaluation of single treatment using concentrations of 5, 20, 50, 100,125, and 250 µg/ml of MEE reduced cell viability 24 hours post-treatment. 5, 50, and 250 µg/ml of MEE was chosen as the combination concentrations with 1000 µM 5-FU. MTT assay 24 hours and 48 hours post-combination treatment showed significant cell viability reduction in comparison to those of single treatments. Apoptosis observation using the double staining method shows the presence of apoptotic cells 48 hours post combination treatment. MEE is a potential co-chemotherapy agent  by increasing the sensitivity  of WiDr colon cancer cell line towards 5-FU.
Hesperidin Increases Cytotoxic Activity of Doxorubicin on Hela Cell Line Through Cell Cycle Modulation and Apoptotis Induction Kusharyanti, Indri; Larasati, .; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 2, No 2 (2011)
Publisher : Indonesian Research Gateway

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Combination of chemotherapeutic agent and chemo preventiveagent is being a new approach in cancer treatment.This is aimed at enhancing the effectivity and also reducing drugresistance and adverse side effect of the chemo therapeuticagent.Hesperidin,acitrus flavonoid has reported to reduce theproliferation of many cancer cells.The objectives of this study were to investigate cytotoxic activities, cell cycle modulation and apoptosis induction of he speridinand its combination withdoxorubicinon Helacelllines.MTT [3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay was used tomeasure the growth inhibitory effect of he speridinanditscombination with doxorubicinon Helacells.Cellcycle profile was determined by flowcytometry and the dataobtained was analyzed by using Mod Fit LT3.0program.Apoptos is assay was done using double staining method usingethidium$bromideandacridine$orange.Hesperidin inhibited cellgrowth with IC5048M, while the IC50 of doxorubicin was 1000nM.Combination of 500n Mdoxorubicin and 6M hesperidin showed strongest inhibitory effect toward Hela cells. Hesperidin of 24 2M accumulated HeLacells at G1phase,butit scombinationwith 500nM Doxorubicin gave G1 and Sphase accumulation at 24h incubation.Both of Hesperidin and Doxorubicin were capable of inducing apoptosis.Inaccordance of the apoptoticeffect,hesperidin,doxorubicin and their combination decreasedthe expression Bcl$2 and increased the expression of Bax. Accordingtothisresult,hesperidinhasapotencytobedevelopedasco$chemotherapeutic agent forcervical cancer. Key    words:Cochemotherapy,Hesperidin,Doxorubicin,Hela,MTTassay
Antiproliferative Effect and Apoptosis Induced in Human Cell Lines by Bruguiera gymnorhiza Barks Methanol Extract Warsinah, .; Sismindari, .; Susidarti, Ratna Asmah
Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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The Antiproliferative effects of methanol extract from Bruguiera gymnorhiza (B. gymnorhiza) barks were tested in vitro against three human cell lines: Hela, Raji and Myeloma cells. The extract was found to have antiproliferative effects against Hela, Raji and Myeloma cells with an IC50 value of 133, 504 and 384 µg/mL, respectively. The antiproliferative test was then performed on Hela, Raji,  and  Myeloma  cells.  Cytotoxicity  assay  of  the  extract  was  then  determined  using  MTT method.  There  were  some  indications  of  apoptosis,  such  DNA  fragmentation,  as  assessed  by acrydine orange- ethidium bromide staining. These results indicate that extract from B. gymnorhiza barks can induce apoptosis in human cell lines.Key words: Antiproliferative, Apoptosis, B. gymnorhiza
Naringenin Enhances the Anti-Tumor Effect of Doxorubicin on HeLa Cervical Cancer Cells Through Cytotoxic Activity and Apoptosis Induction Larasati, .; Kusharyanti, Indri; Hermawan, Adam; Susidarti, Ratna Asmah; Meiyanto, Edy
Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Research Gateway

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Naringenin, an abundant flavanon in the peel of citrus fruits is reported to possess anti-proliferative  effect  in  many  cancer  cells.  Herein,  we  investigated  the  cytotoxic  effect  and apoptosis  induction  of  naringenin  in  combination  with  doxorubicin  on  HeLa  cells.  The cytotoxicity assay of naringenin, doxorubicin, and their combination were carried out by using MTT  assay.  Cell  viability  was  used  as  the  parameters  to  evaluate  combination  effectiveness. Cell  cycle  distribution  was  determined  by  flow  cytometry  and  analyzed  using  ModFit  LT  3.0 program.  Apoptosic  assay  was  done  by  double  staining  method  using  Ethidium  Bromide-Acridine  Orange.  Investigation  on  the  expression  of  Bax  and  Bcl-2  were  determined  by immunocytochemistry method. Naringenin and doxorubicin showed cytotoxic effect  on HeLa cells  with  their  IC50  values  of  195  µM  and  1  µM,  respectively.  Whereas  combination  of naringenin  -  doxorubicin  showed  greater  cytotoxicity  compared  the  single  treatment  of doxorubicin.  The  strongest  cytotoxic  activity  was  observed  at  a  combination  of  100  µM naringenin  and  0,5  µM  doxorubicin.  Single  treatment  of  0,5  µM  doxorubicin  for  24  hours  on HeLa cells induced  S-phase arrest while 100 µM naringenin did not affect on HeLa cell cycle. The  combination  induced  S-phase  arrest  with  the  increased  of  sub-G1  phase  percentage.  In accordance with the flow cytometry results, the double staining apoptosis assay results showed the increase of apoptotic cells. Naringenin, doxorubicin, and their combination also increased the  expression  of  Bax  and  decreased  the  expression  of  Bcl-2.  These  results  concluded  that naringenin was a potential co-chemotherapy agent for cervical cancer due to its synergism with doxorubicin.Keywords:  co-chemotherapy,  naringenin,  doxorubicin,  HeLa  cells,  cytotoxicity,  cell  cycle, apoptosis
Combination of Doxorubicin and Areca Ethanolic Extract Induces Apoptosis by Increasing Caspase-3 Level on Breast Cancer (T47D) Cells Rahmi, Fitria; Meiyanto, Edy; Susidarti, Ratna Asmah
Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Research Gateway

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Despite causing many side effects, doxorubicin (Dox) is still one of breast cancer drug of choice. Thus, combination of chemotherapy is developed in order to decrease doxorubicin regimen dose. The aim of this research is to examine the combination effect of doxorubicin (dox) and areca extract (AE) on T47D human breast cancer cells. The cytotoxic activity was determined using MTT assay. The combination index (Cl) of the combination treatment was calculated to determine the effects (synergistic, additive or antagonistic). The combination application of dox (6-22nM) and AE (8-30μg/ml) on T47D cells showed synergistic (Cl<0.9) or addictive effect )Cl =0.9-I.I). The effective combincation of dox-AE was 6nM-8μg/ml on Cl<0.5. Apoptosis induction of AE solely and its combination with dox was the observed using double staining method. Moreover, expression of Bax and caspase-3 protein which mediated apoptosis, were observed using immunocytochemistry. Combination of AE and Dox increased expression of Caspase-3 but did not increase expression of Bax. This result showed AE increase the effectiveness of doxorubicin against T47D cells.Keyword : Breast cancer, doxorubicin, areca extract, T47D cells
The Safety of Areca Seed Ethanolic Extract as Potential Chemopreventive Agent is Proven by Acute Toxicity Test Handayani, Sri; Jenie, Riris Istighfari; Susidarti, Ratna Asmah
Indonesian Journal of Cancer Chemoprevention Vol 3, No 1 (2012)
Publisher : Indonesian Research Gateway

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Areca (Areca catechu L.) seeds ethanolic extract (AE) exhibits antiproliferative activity and induces apoptosis on T47D and MCF-7 cells. This study aimed to verify AE safety using acute toxicity test to support its development as chemopreventive agent. Male Sprague Dawley Rat 9Rattus norvegicus) age 8 weeks divided into five groups, one group of control treated with 0.5 % CMC-Na only and four groups for treatment. Single dose in oral administration was done to test animal with various dose of AE starts from lowest dose to highest dose expected toxic to all of test animal (0.1; 0.72; 5.36 and 10 gram/kgBW). Observation was done during 24 hours and continued for 14 days. The observation criteria were toxic symptoms, appearance and mechanism of toxic effect and pathology of vital organ. Histopathology analysis of some vital organs was done with Haematoxyllin & Eosin (H&E) staining. Toxic effect did not appear either on treatment groups or control group. Treatment of single dose of areca ethanolic extract, even in highest dose, did not cause the death of the animals. Therefore, observation extended to 14 days and terminated by necroption of the animals. All of group did not show histopathological alterations in microscopic observation. Category of the potential toxicity of AE is practically non-toxic, ie 10 g/kgBW. The result show the safety of areca seed ethanolic extract which is important for its development as chemopreventive agent.Key words: Areca catechu, acute toxicity, rat
Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico Sugiyanto, Raisatun Nisa; Khamsita, Rahmi; Lambertus, Marvin; Utomo, Rohmad Yudi; Susidarti, Ratna Asmah
Indonesian Journal of Cancer Chemoprevention Vol 3, No 2 (2012)
Publisher : Indonesian Research Gateway

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The menopause women have the low level of estrogen in the body. The lack of estrogen changes physiological function in womens body that affects in health condition. Carica papaya L. leaf contains flavonoid quercetin which exhibits estrogenic effect. The aim of this study is to determine the estrogenic effect of papaya leaves extract (PLE) in vivo, and in silico. Papaya leaves were extracted by ethanol 70% maceration. The in silico study were done by molecular docking between quersetin and Estrogen Receptor (ERα and ERß) to obtain the docking score. Based on this study, docking score of quercetin was almost similar to the native ligand of ER. The in vivo study was done as follow: 36 female rats Sprague Dawley divided into six groups. The groups are shame-ovariectomized (S-OVX), control ovariextomized (OVX), CMC-Na control (OVX+CMC-Na), positive control (OVX+Estradiol), and the PLE treatment groups dose 750 mg/kgBW (OVX+750mg/kgBW) and dose 1000 mg/kgBW (OVX+1000 mg/kgBW). Administrations of PLE were done in three weeks orally, while estradiol was administrated intraperitonially. The mammae and uterine were sliced for analysis. Based on the study, the treatment of PLE increased the number of mammae lobules and uterine weight as well as estrogen does. In summary, PLE can be developed as a source of phytoestrogens.Keywords: Carica papaya L., phytoestrogen, estrogen receptor, mammae lobule, uterine
Co-Authors . Larasati . Mustofa . Sarmoko . Sismindari . Warsinah Abdul Karim Zulkarnain Abdul Manaf Ali, Abdul Manaf Adam Hermawan Aditya Fitriasari Agung Endro Nugroho Agustinus Yuswanto, Agustinus Alfi Yasmina Andrih Rianti, Andrih Aulia Katarina Bambang Sulistyo Ari Sudarmanto, Bambang Sulistyo Ari Dyaningtyas Dewi Pamungkas P, Dyaningtyas Dewi EDIATI, EDIATI Edy Meiyanto Endah Puji Septisetyani, Endah Puji Ertanto, Yogi Esti, Yuni Fajar Fany Mutia Cahyani Fitria Rahmi Hari Susanti Hazar B.M. Ismail, Hazar B.M. Herwandhani Putri Husnaa, Ulfatul Ika Puspita Sari Ikawati, Muthiâ?? Ikawati, Muthi’ Indah Purwantini Indri Kusharyanti Inna Armandari Julius Kulip, Julius KARAMITA, ANNISA Kartika Dyah Palupi Kholid Alfan Nur Larasati Larasati M. Aspollah Sukari, M. Aspollah Mahardika Agus Wijayanti Marchaban Marchaban, Marchaban Marvin Lambertus Marwadi Rahmani, Marwadi Maulita Cut Nuria Mintarsih, Betty Mintarsih, Betty Muflikhasari, Haruma Anggraini Mustofa Mustofa Muthi Ikawati Ni Putu Linda Laksmiani Nur Ismiyati Peter G. Waterman, Peter G. Pudjono Pudjono Rachel Turalely Rahmani, Mawardi Rahmani, Mawardi Rahmi Khamsita Raisatun Nisa Sugiyanto Riris Istighfari Jenie Rohmad Yudi Utomo Saputra, Andy Kurniawan Sari, Nur Fitra Sendy Junedi, Sendy Sismindari Sismindari Sofa Farida Sri Handayani Sri Noegrohati Subagus Wahyuono Sudibyo Martono Sukari, Mohd. Aspollah Sukari, Mohd. Aspollah Wahyono ., Wahyono Wahyono Wahyono Warsinah Warsinah Wibowo, Andi Eko Wibowo, Andy Eko Wikanthi, Layung Sekar Sih Wulandari, Nindi Yuli Puspito Rini, Yuli Puspito Zalinar Udin