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POTENSI EKSTRAK ETANOLIK KULIT BUAH JERUK NIPIS (Citrus aurantiifolia (Cristm.) Swingle) SEBAGAI AGEN KHEMOPREVENTIF MELALUI PENEKANAN EKSPRESI c-Myc DAN PENGHAMBATAN PROLIFERASI PADA SEL PAYUDARA TIKUS GALUR SPRAGUE DAWLEY TERINDUKSI 7,12-DIMETILBENZ[a]ANTRASENA Dewi Pratiwi; Novi Hastuti; Niken Nur W; Inna Armandari; Muthi’ Ikawati; Adam Hermawan; Edy Meiyanto
Majalah Obat Tradisional Vol 15, No 1 (2010)
Publisher : Faculty of Pharmacy, Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (702.754 KB) | DOI: 10.22146/tradmedj.8063

Abstract

The using of natural-based medicine is growing rapidly in societies. Besides being cheap and affordable, natural-based medicine is relatively safer than the synthetic drugs. Peel of Citrus aurantifolia (Cristm.) Swingle) is one of the chemopreventive agent which contain flavonoids have potency as anticarcinogenic agent. This study is designed to study the potency of Citrus aurantifolia peel ethanolic extract in proliferation inhibition of Rattus norvegicus mammary cell of Sprague Dawley strain which is induced by 7,12-Dimethylbenz[a]anthracene (DMBA). Rats were divided into five groups consist of DMBA treatment, CMC-Na treatment, extract 1500 mg/kgBW treatment, treatment of DMBA+ extract 750 mg/kgBW and DMBA+ extract 1500 mg/kgBW. At the beginning of the tenth week of the study, breasts was isolated and stored in 10% formalin buffer. Observation of cell proliferation was done by AgNOR method. C-Myc expression observed using immunohistochemistry (IHC). Observation of mammary cell with AgNOR method indicated that the treatment of Citrus aurantifolia peel ethanolic extract can inhibit cell proliferation significantly. Dosage 1500 mg/kgBW gave higher inhibition effect than dosage 750 mg/kgBW. IHC result showed that treatment of Citrus aurantifolia peel ethanolic extract decrease the expression of c-Myc. Dosage 750 mg/kgBW gave lower decreasing effect than dosage 1500 mg/kgBW. Citrus aurantifolia peel ethanolic extract inhibited the proliferation of mammary cell induced DMBA through the inhibition of c-Myc expression in dose dependent phenomena so that it is a potential chemopreventive agent.
Effects of Peel Extract from Citrus reticulata and Hesperidin, A Citrus Flavonoid, on Macrophage Cell Line Muthi’ Ikawati; Inna Armandari; Annisa Khumaira; Yogi Ertanto
Indonesian Journal of Pharmacy Vol 30 No 4, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjpharm30iss4pp260

Abstract

The extract of Citrus reticulata has been studied for its biological activities, due to its citrus flavonoid content. The extract and its flavonoid compounds exhibit growth inhibition properties in several cancer cell lines and in vivo models. Conversely, the extract can also induce cell proliferation and angiogenesis, and shows estrogenic effects, in vitro and in vivo. Because of the contrasting effects that depend on the concentration or dosage, the precise action of the extract and its flavonoids need to be elucidated in various cell types. The objective of this study is to evaluate the effect of Citrus reticulata peel extract (Citrus extract) and hesperidin, a citrus flavonoid, on the modulation of cell proliferation in the RAW 264.7 macrophage cell line. Cell viability under Citrus extract or hesperidin treatment was assessed by using the MTT assay. The expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, modulated by Citrus extract was also examined by immunostaining. Low concentrations of Citrus extract at 1 and 100 μg/mL were able to induce cell proliferation, though not significantly, as shown by cell viability of 138 and 114%, respectively. At higher concentrations of 500, 750, and 1000 μg/mL, Citrus extract decreased cell viability significantly by up to 64, 46, and 36%, respectively. Accordingly, hesperidin at low (3.1 μg/mL−61.1 μg/mL) or high (152.6 μg/mL−305.3 μg/mL) concentrations increased or reduced cell viability significantly by up to 116−136% or 10−61%, respectively. The value of the 50% inhibitory concentration (IC50) of Citrus extract was more than three times higher (756 μg/mL) than that of hesperidin (203 μg/mL = 332 μM). Additionally, 250 μg/mL of Citrus extract was able to induce IL-10 expression compared with the control. These results demonstrate that Citrus extract and hesperidin exert a biphasic effect on macrophage cells. The future development of Citrus extract as a co-chemotherapeutic, anticancer, or immunomodulatory agent should include careful consideration of its biphasic effect on each cell type.
Anti-Osteoporosis Potencies of Zingiber officinale Rosc. Rhizome Water Extract and DFA III Produced from Dahlia spp. L.: in vivo and in vitro Studies Muthi’ Ikawati; Yogi Ertanto; Een Sri Endah; Sri Pudjiraharti; Edy Meiyanto; Riris Istighfari Jenie
The Indonesian Biomedical Journal Vol 14, No 1 (2022)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v14i1.1787

Abstract

BACKGROUND: Zingiber officinale Rosc. is estrogenic and thus can be developed as an anti-osteoporosis. Difructose anhydride III (DFA III), possesses anti-osteoporosis potencies. This study aimed to investigate the anti-osteoporosis activity of ginger rhizome water extract (GE) and DFA III from dahlia tubers in ovariectomized (OVX) rat models and to determine their anti-osteoclastogenic effect in vitro.METHODS: This study was conducted using 25 female rats. Blood sampling was carried out at the beginning and end of treatments. Femur bones were isolated after daily 14-day treatments, measured for density, and processed for histological staining. RAW 264.7 cells were induced by osteoclast differentiation factor. A cell viability assay was employed to determine the cytotoxicity of DFA III and GE. The inhibition of osteoclastogenesis was investigated by tartrate-resistant acid phosphatase staining.RESULTS: All groups showed no difference in body weight elevation and serum lipid profiles. The GE and DFA III caused no effect on bone density. However, the GE or DFA III groups showed higher osteoblast numbers compared with the control groups. A significantly less osteoclast was found in the GE+DFA III group. The GE and DFA III showed no toxicity on RAW 264.7 cells. GE showed strong inhibitory effects on the post stimulation osteoclastogenesis model. The combination of GE and DFA III was synergistic in reducing the osteoclastogenesis confluency in RAW 264.7 cells.CONCLUSION: The data support our hypothesis that GE and DFA III can decrease the risk of osteoporosis by osteoclastogenesis inhibition.KEYWORDS: Dahlia spp., estrogenic, ginger, osteoclast, osteoporosis, ovariectomy, RAW 264.7 cell
Curcumin Analogs, PGV-1 and CCA-1.1 Exhibit Anti-migratory Effects and Suppress MMP9 Expression on WiDr Cells Febri Wulandari; Muthi' Ikawati; Mitsunori Kirihata; Jun-Ya Kato; Edy Meiyanto
The Indonesian Biomedical Journal Vol 13, No 3 (2021)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v13i3.1583

Abstract

BACKGROUND: Colon cancer is still a crucial concern in the development of chemotherapeutic drugs due to the drug resistance phenomenon and various side effects to patients. One of the newest compound that show anticancer activities against several cancer cells, Chemoprevention Curcumin Analog 1 (CCA-1.1), has increasingly been explored to overcome the limitation of conventional drugs.METHODS: We evaluated the anti-migratory effect of CCA-1.1 and Pentagamavunone-1 (PGV-1) by using WiDr colon cancer cells. The expression profiles of Tumor Protein 53 (TP53) and Matrix Metalloproteinase-9 (MMP9) in colon cancer were obtained from the UALCAN database. Survival outcomes of TP53 and MMP9 in colon cancer patients were analyzed using the Kaplan-Meier method. We used 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), scratch wound healing, and gelatin zymography assays to observe the cytotoxic effect, anti-migratory activity, and MMP9 expression, respectively, in CCA-1.1 or PGV-1-treated cells.RESULTS: Level of MMP9 was found significantly overexpressed in the primary tumor and metastasis nodal, while TP53 mutation sample types were observed and influenced the survival outcome in colon cancer patients. CCA-1.1 and PGV-1 exhibited strong cytotoxic activity after 24 and 48 h treatment against WiDr cells. The migration assay demonstrated that PGV-1 and CCA-1.1 at 1 mM inhibited cell migration up to 40% after 48 h in single and combination with doxorubicin. The MMP9 expression was significantly inhibited by 0.5 mM CCA-1.1.CONCLUSION: This study emphasizes that the anti-migratory effect of CCA-1.1 is better than PGV-1 via MMP9 suppression on WiDr. Thus, CCA-1.1 is prominent to be developed as an anti-metastatic agent.KEYWORDS: chemopreventive curcumin analog 1.1 (CCA-1.1), PGV-1, WiDr cells, anti-migration, MMP9
Banana Peels (Musa paradisiaca L.) Extract as Phytoestrogen on Ovariectomized Mice Mammary Gland Development by Inducing c-Myc Expression Nanda Resa Pratama; Yurista Gilang; Rita Riata; Adam Hermawan; Muthi' Ikawati; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev2iss1pp151-158

Abstract

Hormone Replacement Therapy (HRT) is therapy for estrogen deficiency and post menopausal syndromes, but high cost and unwell-secured therapy. One of alternative therapy is the usage of phytoestrogens. The banana peel contains flavones, flavonol, flavanone and polimethoxyflavone which are potential as phytoestrogen. The purpose of this study was to examine the estrogenic effect of banana peel extract (BPE) development of mammary gland of ovariectomized rats. Estrogenic effects was examined based on in vivo and in silico experiment. For in vivo experiment, female Sprague-dawley rats aged 50 days were ovariectomized. At 70 days of age, 12 rats were treated with BPE 500 mg/kgBB and 1000mg/kgBB, 5 rats were treated with estradiol 2μg/day while others served as control were treated with CMC-Na 0.5% and sacrificed 2 weeks later. The base line ovariectomized rats and base line non-ovariectomized rats were sacrificed at 70 days of age. The in silico experiment examined by molecular docking between myricetin and estrogen receptor alpha (ER-α). The result of in vivo experiment showed that 1000 mg/kgBW BPE induced c-Myc expression and enhance ovariectomized rat mammary gland development significantly. Meanwhile, molecular docking showed that there are hydrogen bond interaction between bioactive compound in BPE and Estrogen Receptor (ER)-α but less powerfull than estrogen and ER-α interaction. In summary, BPE can act as an estrogen agonist, resulting in the enhancement of c-Myc expression.Keywords: banana peels extract (BPE), phytoestrogen, mammary gland, ovariectomized rats
Anti-metastatic Profiles of Boesenbergia pandurata towards MCF-7/HER2 Cells Hilyatul Fadliyah; Nindya Budiana Putri; Ziana Walidah; Ika Putri Nurhayati; Muthi Ikawati; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 9, No 2 (2018)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev9iss2pp68-77

Abstract

The development of breast cancer at an advanced stage is signed with metastatic phenomenon, triggering the high mortality, mainly for Human Epidermal Growth Factor Receptor (HER)2 positive cancers. Boesenbergia pandurata is well known as medicinal plant possessing anticancer potential due to the cytototoxic and antimetastatic characteristic of its active compound. The aim of this study is to observe the inhibitory effect of Boesenbergia pandurata ethanolic extract (BPEE) in combination with doxorubicin on migration of MCF-7/HER2 cells. The BPEE was prepared by 96% ethanol maceration. Under MTT assay, BPEE decreased the cells viability with IC50 value of 23±3.9 μg/mL. Lamellipodia and wound healing assay analysis showed that 5 μg/mL BPPE and its combination with 10 nM doxorubicin inhibited cells migration after 48 hours observation, while gelatin zymography analysis showed that this combination did not affect the expression of Matrix Metalloproteinase (MMP)2 and MMP9, but single treatment of 5 μg/mL BPEE caused lower expression of both MMPs. The combination of 5 μg/mL BPPE and 10 nM doxorubicin inhibited the cells migration but not affect to the cells viability. Thus, BPEE is potential to be developed as an antimetastatic agent. The mechanism underlying the migratory inhibition effect needs to be explored further.Keywords : Boesenbergia pandurata, doxorubicin, MCF-7/HER2, migrationSubmitted:
Phytochemical and Bioinformatic Studies of Citrus Flavonoids as Chemopreventive Agents Targeting GGPS1 for Liver Cancer Ratih Kurnia Wardani; I Made Rhamandana; Christina Mutiara Putri Gono; Muthi Ikawati
Indonesian Journal of Cancer Chemoprevention Vol 12, No 3 (2021)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev12iss3pp137-147

Abstract

Overexpression of geranylgeranyl diphosphate synthase 1 (GGPS1) is an unfavorable prognosis in liver cancer development. The side effects of therapeutic standards encourage the development of therapeutic agents from herbal materials. Citrus peels are rich of phytochemical compounds, especially citrus flavonoids, that possess cytotoxic activities. This study aimed to determine the potential of citrus flavonoids as chemopreventive agents targeting GGPS1 protein by phytochemical and bioinformatic studies. Dried peels of Citrus reticulata were extracted by hydrodynamic-cavitation method followed by identification of compounds using thin layer chromatography (TLC). The expression level of GGPS1 was obtained from UALCAN, while its correlation with survival rate was obtained from the GEPIA. Prediction models regarding the potential inhibitors of citrus peel compounds against GGPS1 were obtained through KNIME and ChEMBl, followed by literature studies on chemopreventive activity of citrus flavonoids. The molecular docking was used to predict the molecular interaction followed by tracking of target genes that were positively correlated with GGPS1 by SwissTargetPrediction. Yielded 75% (v/v), the extract positively contained citrus flavonoid with hesperidin as comparison. Overexpression of GGPS1 significantly reduced the survival rate of liver cancer patients (p value=0.019). Four citrus flavonoid compounds, namely tangeretin, nobiletin, hesperidin, and naringenin showed potential inhibition to GGPS1. The molecular docking showed that tangeretin had a strong affinity compared to the native ligand and zoledronic acid, as positive control. PARP1, CSNK2A1, TNKS2, and GSK3B were clarified as targeted genes for tangeretin and nobiletin that positively correlated with GPPS1. In vitro and in vivo studies will validate our findings and support the development of citrus peel extract with rich flavonoid contents as a chemopreventive agent.Keywords: geranylgeranyl diphosphate synthase 1 (GGPS1), liver cancer, hydrodynamic-cavitation, citrus flavonoid, bioinformatic.
The Chemopreventive Potential of Diosmin and Hesperidin for COVID-19 and Its Comorbid Diseases Rohmad Yudi Utomo; Muthi' Ikawati; Dyaningtyas Dewi Pamungkas Putri; Irfani Aura Salsabila; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 11, No 3 (2020)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev11iss3pp154-167

Abstract

The COVID-19 becomes worse with the existence of comorbid diseases such as cardiovascular diseases, metabolic syndromes, inflammation, degenerative diseases, as well as cancer. Therefore, a comprehension approach is needed to combat such comorbid conditions, not only focusing on the virus infection and replication but also directed to prevent the raising comorbid symptoms. This study analyzed the potential natural compounds, especially diosmin and hesperidin, as an anti-SARS-CoV-2 and chemopreventive agent against several COVID-19 comorbid diseases by using an in-silico method. Diosmin and hesperidin together with other natural compounds and existing viral drugs (lopinavir, nafamostat, and comastat) were docked into several proteins involved in SARS-CoV-2 infection and replication namely SARS-CoV-2 protease (PDB:6LU7), spike glycoprotein-RBD (PDB:6LXT), TMPRSS2, and PD-ACE2 (PDB:6VW1) using MOE software. The interaction properties were determined under docking score values. The result exhibited that diosmin and hesperidin performed superior interaction with all the four proteins compared to the other compounds, including the existing drugs. Moreover, under literature study, diosmin and hesperidin also elicit good chemopreventive properties against cardiovascular disorder, lung and kidney degeneration, as well as cancer development. In conclusion, diosmin and hesperidin possess high opportunity to be used for the COVID-19 and its the comorbid diseases as chemopreventive agents.Keywords: chemoprevention, COVID-19, diosmin, hesperidin, SARS-CoV-2 infection
Taraxacum officinale Leaves Ethanolic Extract as Immunostimulatory Agent For Reducing Side Effect of Doxorubicin in Sprague Dawley Rats Sri Kasianningsih; Erlina Rivanti; Ratih Hardika Pratama; Nanda Resa Pratama; Muthi' Ikawati; Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention Vol 2, No 1 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev2iss1pp135-140

Abstract

Doxorubicin as chemotherapeutic agent causes immunosuppresive. The aim for this study to determine the effect of ethanolic extract of Taraxacum oficinale (ETO) in immunity system of Sprague Dawley rat that induced by doxorubicin to observe the profile of immunity cells. Sprague Dawley rats were divided into five groups each groups contain five rats: control doxorubicin group, doxorubicin dose 4,67 mg/kgBW+ ETO dose 1000 mg/kgBW, doxorubicin dose 4,67 mg/kgBW+ ETO dose 500 mg/kgBW, control extract group, and without treatment. Then the number of leukocytes, lymphocytes and neutrophils were analyzed by hematology analyzer, whereas CD8+ T lymphocytes by flowcytometry. Results showed groups of doxorubicin combined with ETO dose 1000 mg/kgBW and 500 mg/kgBW increased the number of leukocytes, lymphocytes, neutrophils,  cytotoxic CD8 + T cells T cells compared to control doxorubicin group. These data presents that etanolic extract of Jombang leaves has immunostimulatory activity and potential as co-chemotherapy agents. Molecullar mechanism underlaying it’s immune activity need to be explored in detail.Keywords: co-chemotheraphy, doxorubicin, immunostimulatory, in vivo Taraxacum officinale
The Cytotoxic Activity of Solanum Nigrum Ethanolic Extract on Widr Human Colon Cancer Cells Astrid Ayu Maruti; Ilham Augusta F.; Dyaningtyas Dewi Pamungkas Putri; Adam Hermawan; Muthi' Ikawati
Indonesian Journal of Cancer Chemoprevention Vol 2, No 3 (2011)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev2iss3pp291-294

Abstract

Solanum nigrum L. or Leunca in Indonesia has been traditionally used as a herbal plant, which is believed to have anti-tumor properties, although the mechanism for the activity remains unknown. The resecarch aim to examine the cytotoxic effect of the ethanolic extract of Solanum nigrum on WiDr human colon cancer cells. In this study, we prepared an ethanol extract from herb of Solanum nigrum and investigated the mechanism involved in its growth-inhibitory effect on WiDr human colon cancer cells. Herbs of Solanum nigrum dry powder is extracted with 70% ethanol then added into the WiDr cell culture in 96 wells plate in various concentration : 50, 100, 250, and 500 µg/ml. Cytotoxicity of the Solanum nigrum ethanolic extract  was analyzed with MTT assay on WiDr human colon cancer cell lines. Results from the MTT assay showed WiDr cells was weakly suppressed in the presence of the extract. The result of the assay also showed a very close correlation between the Solanum nigrum extract concentration and the surviving cell numbers which means the extract caused cell death in a dose-dependent fashion in WiDr cancer cells with the IC50 of 359,23 µg/ml. Collectively, the research suggest further studies to explore other chemopreventive possibilites of Solanum nigrum ethanolic extract.Keywords : colon cancer, MTT assay, cytotoxic, WiDr, Solanum nigrum
Co-Authors . Anindyajati Abdul Manaf Ali, Abdul Manaf Adam Hermawan ADTYA FITRIASARI Afifah, Anis Afivah Dewi Anggraeni Agusta Fauzi, Ilham Alfi Yasmina ANINDYAJATI ANINDYAJATI Anindyajati Anindyajati ANNISA KARAMITA Annisa Khumaira Arief Nurrochmad Astrid Ayu Maruti Astrid Ayu Maruti Bayu Anggoro Christina Mutiara Putri Gono Dennaya Kumara Dewi Pratiwi Dewi Pratiwi Dhania Novitasari Dhella Angelina Dhiya Ulhaq Salsabila Dyaningtyas D.P. Putri Dyaningtyas Dewi Putri Pamungkas EDIATI EDIATI Ediati Sasmito Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto EDY MEIYANTO Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Een Sri Endah Endah Puji Septisetyani Endah Puji Septisetyani, Endah Puji Erlina Rivanti Erlina Rivanti Febri Wulandari Fikri Amalia Gono, Christina Mutiara Putri Hanifa, Mila Hilyatul Fadliyah I Made Rhamandana Ibrahim Arifin Ika Puspitaningrum Ika Putri Nurhayati Ilham Augusta F Ilham Augusta F. Imaniyyati, Niar Nurul Inna Armandari Inna Armandari Irfani Aura Salsabila Jenie, Riris Istighfari Jun-ya Kato Jun-Ya Kato Mintarsih, Betty Mintarsih, Betty Mitsunori Kirihata Moordiani Moordiani Muhammad Novrizal Abdi Sahid Mustofa Mustofa Nanang Fakhrudin, Nanang Nanda Resa Pratama Nanda Resa Pratama Natasia, Nyssa Niken Nur W Niken Nur W, Niken Nindya Budiana Putri Normaidah, Normaidah Novi Hastuti Novi Hastuti, Novi Nurma Sabila Nurramadhani A. Sida Purwanto, Heri Rahmani, Mawardi Rahmani, Mawardi RATIH HARDIKA PRATAMA Ratih Hardika Pratama Ratih Hardika Pratama Ratih Kurnia Wardani Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Asmah Susidarti Rifai, Fauziah Novita Putri RIRIS ISTIGHFARI JENIE Rita Riata Rita Riata Ritmaleni, Ritmaleni Rohmad Yudi Utomo Sagiyo, Marrita Langgeng Sari Haryanti Sari Haryanti Shirly Kumala Sismindari, Sismindari Sri Handayani Sri Kasianningsih Sri Kasianningsih Sri Pudjiraharti Sukari, Mohd. Aspollah Sukari, Mohd. Aspollah Susi Ari Kristina Susi Ari Kristina Susi Ari Kristina Syifa Athia Zainun Faqiha Tafrihani, Ahmad Syauqy Wulandari Wulandari Yogi Ertanto Yogi Ertanto Yohanes, Jasson Yurista Gilang Yurista Gilang YURISTA GILANG IKHTIARSYAH Ziana Walidah Zulfin, Ummi Maryam