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All Journal Indonesian Journal of Cancer Chemoprevention Journal of Mathematical and Fundamental Sciences Indonesian Journal of Biotechnology Majalah Obat Tradisional Journal of Tropical Biodiversity and Biotechnology INDONESIAN JOURNAL OF PHARMACY The Indonesian Biomedical Journal JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice) JPSCR : Journal of Pharmaceutical Science and Clinical Research JFIOnline Jurnal Ilmu Kefarmasian Indonesia Majalah Kesehatan Pharmamedika
Muthi Ikawati
Faculty Of Pharmacy, Universitas Gadjah Mada
Agriculture, Biological Sciences & Forestry Astronomy Biochemistry, Genetics & Molecular Biology Chemistry Earth & Planetary Sciences Environmental Science Health Professions Immunology & microbiology Materials Science & Nanotechnology Mathematics Medicine & Pharmacology Physics Public Health

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Journal : The Indonesian Biomedical Journal

 1 
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
Curcumin Analogs PGV-1 and CCA-1.1 Induce Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells with Overexpressed MYCN Moordiani Moordiani; Dhania Novitasari; Ratna Asmah Susidarti; Muthi' Ikawati; Jun-ya Kato; Edy Meiyanto
The Indonesian Biomedical Journal Vol 15, No 2 (2023)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v15i2.2147

Abstract

BACKGROUND: Liver cancer is the third leading mortality in cancer. Curcumin shows effective anticancer potency against various cancer including liver cancer. The synthesized curcumin analog compounds Pentagamavunone-1 (PGV-1) and Chemoprevention Curcumin Analog-1.1 (CCA-1.1) have been well studied in breast, leukemia, and colon cancer cells with better potency than curcumin itself, yet their cytotoxic activities were not known in liver cancer cells. Thus, this study was conducted to elevate the anticancer effect of these curcumin analogs against hepatocellular carcinoma (HCC) cells in vitro, specifically in MYCN-expressing cells, based on its cellular physiology.METHODS: JHH-7 cells were used as the HCC cell model with high expression of MYCN. The viability of the cells was observed using trypan blue exclusion method while cell cycle profile and intracellular reactive oxygen species (ROS) levels were quantified by means of flow cytometry. Chromosomal staining with Hoechst was applied to determine the cell cycle arrest phase, whilst X-gal staining was used to assess the cellular senescence activity.RESULTS: The result of current study presented that the growth inhibitory activity of PGV-1 as well as CCA-1.1 in JHH-7 cells was associated with the cell cycle arrest and cellular senescence. Both curcumin analogs PGV-1 and CCA-1.1 ultimately induced mitotic arrest (p<0.001) better than curcumin. Moreover, PGV-1 and CCA-1.1 similarly increased the senescent cells that partly mediated through ROS elevation. The transcription level of MYCN was not altered upon treatment with curcumin and its analogs in JHH-7 cells, suggesting that molecular mechanism of the inhibitory effect was independent from MYCN signaling.CONCLUSION: Taken together, these observations revealed that both PGV-1 and CCA-1.1 potentially serve as multi-targeted curcumin-based compounds and lead to promising anti-hepatocellular cancer agents.KEYWORDS: Curcumin analogs, hepatocellular carcinoma, mitotic arrest, MYCN
Immunomodulatory Effect of Dioscorea esculenta L. on NF-κB, TLR-4, TNF-α, and IL-10 Expressions in LPS-stimulated RAW 264.7 Mouse Macrophages Puspitaningrum, Ika; Ikawati, Muthi; Fakhrudin, Nanang; Nurrochmad, Arief
The Indonesian Biomedical Journal Vol 17, No 3 (2025)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v17i3.3630

Abstract

BACKGROUND: Gene expressions of toll-like receptor 4 (TLR)-4, nuclear factor-kappaB (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 are known to have roles in the inflammatory process and affect the regulation of the immune system. A preliminary study showed that Dioscorea esculenta L. tuber has immunomodulatory activity against macrophage phagocytosis activity and lymphocyte proliferation. However, the immunomodulatory activity of aqueous extract (AE), polysaccharide fraction (PF), and non-polysaccharide fraction (NPF) of D. esculenta L. tubers on these gene expressions have not been elucidated well. Therefore, this study was performed to determine its immunomodulatory activity by utilizing RAW 264.7 cell culture induced by lipopolysaccharide (LPS).METHODS: RAW 264.7 cells were stimulated with LPS at a concentration of 1 µg/mL for 30 minutes before incubation with non-toxic concentrations of AE, PF, NPF, positive control, and inulin at 25 and 50 µg/mL. TNF-α, IL-10, TLR-4, NF-κB, and β-actin expressions were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and were normalized with β-actin as an internal control. Triplicate experiments were performed throughout this study.RESULTS: Treatment with 25 µg/mL NPF significantly decreased the expression of NF-κB, TLR-4, and TNF-α (p<0.05). In contrast, treatment of 25 and 50 µg/mL PF significantly decreased the NF-κB expression (p<0.05). Moreover, only treatment with 50 µg/mL AE exhibited a significant increase in IL-10 expression (p<0.05).CONCLUSION: Treatment with D. esculenta L. tuber stimulated macrophage RAW 264.7 cells via NF-κB, TLR-4, TNF-α, and IL-10 expressions. NPF at 25 µg/mL has stronger immunomodulatory activity in reducing the expression of genes involved in the inflammatory process that plays a role in regulating the immune system.KEYWORDS: Dioscorea esculenta L., Immunomodulator, IL-10, NF-κB, TLR-4, TNF-α, RAW 264.7 cell
Diosmin Enhances the Anti-migration Activity of Curcumin Analog PGV-1 on Colorectal Cancer Cells Ikawati, Muthi; Utomo, Rohmad Yudi; Hapsari, Novia Permata; Meiyanto, Edy; Oka, Chio
The Indonesian Biomedical Journal Vol 16, No 1 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i1.2829

Abstract

BACKGROUND: Diosmin enhances the cytotoxicity of Pentagamavunone-1 (PGV-1) in cancer cells. PGV-1 and diosmin are predicted to target several matrix metalloproteinases (MMPs) in metastatic cancer, including colorectal cancer, but the anti-migration potency of their combination has not established yet. This study evaluates the anti-migration effect of PGV-1 and diosmin combination in colorectal cancer.METHODS: The cytotoxicity assay using Cell Counting Kit 8 (CCK-8) method in WiDr colorectal cancer cells was carried out to determine the concentration for anti-migration experiments. The wound healing assay was used to observe the anti-migration activity by measuring the cell-free area. Gelatin zymography was employed to detect the MMP activity indicating by the clear band density. The interaction between PGV-1 or diosmin and MMP proteins was predicted by molecular dockings.RESULTS: PGV-1 was cytotoxic (IC50 17 mM), while diosmin up to 100 mM did not affect cell viability. Both 10 mM PGV-1 as well as 50 and 100 mM diosmin slowed down the closure of cell-free area. A 100 mM diosmin was significantly enhance the anti-migratory activity of 50 and 100 mM PGV-1. The activity of MMP-9 and MMP-2 was also lower in the presence of diosmin compared to than that of PGV-1 alone. PGV-1 or diosmin was also able to interact with MMP proteins with a lower energy compared to than that of the native ligands.CONCLUSION: Diosmin enhances the anti-migration activity of PGV-1 in WiDr cells, possibly by affecting MMPs’ activity. This study is an evidence that diosmin is a potential co-chemotherapy candidate for PGV-1, that can be utilized to overcome metastatis in colorectal cancer.KEYWORDS: cancer, citrus flavonoid, co-chemotherapy, diosmin, matrix metalloproteinases (MMPs), migration, Pentagamavunone-1, WiDr cancer cell
Co-Authors . Anindyajati Abdul Manaf Ali, Abdul Manaf Adam Hermawan ADTYA FITRIASARI Afifah, Anis Afivah Dewi Anggraeni Agusta Fauzi, Ilham Alfi Yasmina Angelina, Dhella Anggoro, Bayu ANINDYAJATI ANINDYAJATI Anindyajati Anindyajati ANNISA KARAMITA Annisa Khumaira Arief Nurrochmad Astrid Ayu Maruti Astrid Ayu Maruti Chio Oka, Chio Dewi Pratiwi Dewi Pratiwi Dhania Novitasari 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 Hapsari, Novia Permata Hilyatul Fadliyah Ibrahim Arifin Ika Puspitaningrum Ika Putri Nurhayati Ilham Augusta F Ilham Augusta F. Imaniyyati, Niar Nurul Inna Armandari Inna Armandari Jenie, Riris Istighfari Jun-Ya Kato Jun-ya Kato Kumara, Dennaya 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 Putri, Amaliya Permata Rahman, Faaza Aulia Rahmani, Mawardi Rahmani, Mawardi Rahmawati, Desty Restia Ratih Hardika Pratama RATIH HARDIKA PRATAMA Ratih Hardika Pratama Ratna Asmah Susidarti Ratna Asmah Susidarti Ratna Asmah Susidarti Rhamandana, I Made 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 Wardani, Ratih Kurnia Wulandari Wulandari Yogi Ertanto Yogi Ertanto Yohanes, Jasson Yurista Gilang Yurista Gilang YURISTA GILANG IKHTIARSYAH Ziana Walidah Zulfin, Ummi Maryam