Displaying publications 41 - 54 of 54 in total

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  1. Fulltext Dihydrotestosterone, a robust promoter of osteoblastic proliferation and differentiation: understanding of time-mannered and dose-dependent control of bone forming cells
    Thu HE, Mohamed IN, Hussain Z, Shuid AN
    Iran J Basic Med Sci, 2017 Aug;20(8):894-904.
    PMID: 29085581 DOI: 10.22038/IJBMS.2017.9111
    OBJECTIVES: The present study was aimed to evaluate the time-mannered and dose-dependent effects of 5α-dihydrotestosterone (5α-DHT) on the proliferation and differentiation of bone forming cells using MC3T3-E1 cells.

    MATERIALS AND METHODS: Cell proliferation was analyzed using MTS and phase contrast microscopic assays. Osteogenic differentiation was assessed through a series of in vitro experiments including crystal violet staining, alkaline phosphatase (ALP) activity, and Van Gieson (VG) staining. Taken together, the efficiency of bone mineralization was examined by using alizarin red s (ARS) staining, Von Kossa staining, scanning electron microscopy (SEM) and energy dispersive x-ray (EDX) analysis.

    RESULTS: The resulting data revealed that 5α-DHT exhibits promising potential particularly at a dose of 0.1 ng/ml, in promoting the growth of MC3T3-E1 cells compared to the control group (CN). Moreover, a significantly higher ALP activity was evident in the experimental group treated with 5α-DHT compared to the CN group at various time intervals. MC3T3-E1 cells treated with 5α-DHT also expressed a remarkably higher collagen deposition and mineralization (calcium and phosphate contents) compared to the CN group at various time intervals.

    CONCLUSION: Conclusively, we suggest that 5α-DHT exhibits outstanding potential of promoting proliferation and differentiation in osteoblasts which could be the in vitro basis for the efficacy of 5α-DHT in the treatment of androgen-deficient male osteoporosis.

    Matched MeSH terms: Anthraquinones
  2. Nordamnacanthal potentiates the cytotoxic effects of tamoxifen in human breast cancer cells
    Subramani T, Yeap SK, Ho WY, Ho CL, Osman CP, Ismail NH, et al.
    Oncol Lett, 2015 Jan;9(1):335-340.
    PMID: 25435988
    Tamoxifen (TAM) is the mainline drug treatment for breast cancer, despite its side effects and the development of resistance. As an alternative approach, in the present study a novel combination therapy was established through combining TAM with nordamnacanthal (NDAM) in order to investigate the additive effect of these drugs in MCF-7 human breast cancer cells. A significant dose-dependent reduction in cell viability and an increase in apoptosis were observed in the MCF-7 cells cotreated with TAM and NDAM compared with the untreated control cells or the cells treated with TAM and NDAM alone (P<0.05). The cytotoxic influence of the combination of TAM and NDAM was found to be two-fold that of the individual agents. Annexin V/propidium iodide double-staining revealed the typical nuclear features of apoptosis. Furthermore, an increase in the proportion of apoptotic, Annexin V-positive cells was observed with the combination therapy. Moreover, this apoptotic induction was associated with a collapse of the mitochondrial membrane potential and the generation of reactive oxygen species. To the best of our knowledge, the findings of the present study are the first to suggest that combining TAM with NDAM may be a potential combination therapy for the treatment of breast cancer and may have the potential to minimize or eliminate the side effects associated with high doses of TAM.
    Matched MeSH terms: Anthraquinones
  3. Optimization of the Static Human Osteoblast/Osteoclast Co-culture System
    Jolly JJ, Chin KY, Farhana MFN, Alias E, Chua KH, Hasan WNW, et al.
    Iran J Med Sci, 2018 Mar;43(2):208-213.
    PMID: 29749990
    Osteoblasts (OBs) and osteoclasts (OCs) are 2 major groups of bone cells. Their cell-to-cell interactions are important to ensure the continuity of the bone-remodeling process. Therefore, the present study was carried out to optimize an OB/OC co-culture system utilizing the human OB cell line hFOB 1.19 and OCs extracted from peripheral blood mononuclear cells (PBMNCs). It was a 2-step procedure, involving the optimization of the OB culture and the co-culture of the OBs with PBMNCs at an optimum ratio. Firstly, pre-OBs were cultured to 90% confluency and the time required for differentiation was determined. OB differentiation was determined using the van Gieson staining to detect the presence of collagen and Alizarin Red for calcium. Secondly, OBs and OCs were co-cultured at the ratios of 1 OC: 1 OB, 1 OC: 4 OBs, 2 OCs: 1 OB, and 1 OC: 2 OBs. Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the differentiation of the OCs. The results showed that collagen was present on day 1, whereas calcium was detected as early as day 3. Based on the result of TRAP staining, 1 OC: 2 OBs was taken as the most appropriate ratio. No macrophage colony-stimulating factor and receptor activator of the nuclear factor-κB ligand were added because they were provided by the OBs. In conclusion, these optimization processes are vital as they ensure the exact time point and ratio of the OB/OC co-culture in order to produce a reliable and reproducible co-culture system.
    Matched MeSH terms: Anthraquinones
  4. Expression profile of genes modulated by Aloe emodin in human U87 glioblastoma cells
    Haris K, Ismail S, Idris Z, Abdullah JM, Yusoff AA
    Asian Pac J Cancer Prev, 2014;15(11):4499-505.
    PMID: 24969876
    Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
    Matched MeSH terms: Anthraquinones/pharmacology*
  5. Application of Box-Behnken design for ultrasound-assisted extraction and recycling preparative HPLC for isolation of anthraquinones from Cassia singueana
    Jibril S, Basar N, Sirat HM, Wahab RA, Mahat NA, Nahar L, et al.
    Phytochem Anal, 2019 Jan;30(1):101-109.
    PMID: 30288828 DOI: 10.1002/pca.2795
    INTRODUCTION: Cassia singueana Del. (Fabaceae) is a rare medicinal plant used in the traditional medicine preparations to treat various ailments. The root of C. singueana is a rich source of anthraquinones that possess anticancer, antibacterial and antifungal properties.

    OBJECTIVE: The objective of this study was to develop an ultrasound-assisted extraction (UAE) method for achieving a high extraction yield of anthraquinones using the response surface methodology (RSM), Box-Behnken design (BBD), and a recycling preparative high-performance liquid chromatography (HPLC) protocol for isolation of anthraquinones from C. singueana.

    METHODOLOGY: Optimisation of UAE was performed using the Box-Behnken experimental design. Recycling preparative HPLC was employed to isolate anthraquinones from the root extract of C. singueana.

    RESULTS: The BBD was well-described by a quadratic polynomial model (R2  = 0.9751). The predicted optimal UAE conditions for a high extraction yield were obtained at: extraction time 25.00 min, temperature 50°C and solvent-sample ratio of 10 mL/g. Under the predicted conditions, the experimental value (1.65 ± 0.07%) closely agreed to the predicted yield (1.64%). The obtained crude extract of C. singueana root was subsequently purified to afford eight anthraquinones.

    CONCLUSION: The extraction protocol described here is suitable for large-scale extraction of anthraquinones from plant extracts.

    Matched MeSH terms: Anthraquinones/isolation & purification*
  6. Cytochrome P450 2C9-natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from in vitro data
    Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Yiap BC, et al.
    Biopharm Drug Dispos, 2018 Apr;39(4):205-217.
    PMID: 29488228 DOI: 10.1002/bdd.2127
    Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed-type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 μM and Ki of 1.16 μM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro-in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.
    Matched MeSH terms: Anthraquinones/pharmacology
  7. Effects of Damnacanthal and Nordamnacanthal on Proliferation, Apoptosis, and Migration of Oral Squamous Cell Carcinoma Cells
    Shaghayegh G, Alabsi AM, Ali-Saeed R, Ali AM, Vincent-Chong VK, Ismail NH, et al.
    Asian Pac J Cancer Prev, 2017 Dec 29;18(12):3333-3341.
    PMID: 29286228
    Cancer is one of the most common causes of death in the developed world, with one-third of people diagnosed with
    cancer during their lifetime. Oral cancer commonly occurs involving the buccal mucosa (cheeks), tongue, floor of the
    mouth and lip. It is one of the most devastating and disfiguring of malignancies. Morinda citrifolia L., commonly known
    as ‘noni’, belongs to the Rubiaceae family. It is native to the Pacific islands, Hawaii, Caribbean, Asia and Australia.
    The plant displays broad curative effects in pharmacological studies. Damnacanthal (DAM) and Nordamnacanthal
    (NDAM), anthraquinone compounds isolated from the roots of Morinda citrifolia L., has been used for the treatment
    of several chronic diseases including cancer. The objectives of this study were to evaluate cytotoxicity, morphological
    changes, cell death mode (apoptosis/necrosis), and cell migration induced by DAM and NDAM on the most common
    type of oral cancer, oral squamous cell carcinoma (OSCC)cells. Anti-proliferative effects of these compounds against
    OSCC cell lines were determined by MTT assay. The mode of cell death was analysed by phase contrast and fluorescent
    microscopy as well as flow cytometry. In addition, cell migration was assessed. The results showed that DAM and
    NDAM exerted cytotoxicity against OSCC cells with IC50 values of 1.9 to >30 μg/ml after 72 h treatment. Maximum
    growth inhibition among the tested cell lines for both compounds was observed in H400 cells, and thus it was selected
    for further study. The study demonstrated inhibition of H400 OSCC cell proliferation, marked apoptotic morphological
    changes, induction of early apoptosis, and inhibition of cell migration by DAM and NDAM. Therefore, this information
    suggests that these compounds from noni have potential for used as anti tumor agents for oral cancer therapy.
    Matched MeSH terms: Anthraquinones/pharmacology*
  8. Immunomodulatory effects of damnacanthal isolated from roots of Morinda elliptica
    Alitheen NB, Manaf AA, Yeap SK, Shuhaimi M, Nordin L, Mashitoh AR
    Pharm Biol, 2010 Apr;48(4):446-52.
    PMID: 20645725 DOI: 10.3109/13880200903168031
    Morinda elliptica Ridley (Rubiaceae) has been used traditionally as a medicine to treat various diseases in Malaysia and southeast Asia. In the present study we investigated the immunomodulatory effects of damnacanthal isolated from the roots of Morinda elliptica. The immunomodulatory effect of this compound was evaluated by using the lymphocyte proliferation assay with mouse thymocytes and human peripheral blood mononuclear cells (PBMC). In addition, the effect of the compound on PBMC cell cycle progression was studied by using flow cytometry. The production of human interleukin-2 and human inteleukin-12 cytokines was also assessed using the enzyme linked immunosorbent assay (ELISA) technique. The lymphocyte proliferation assay showed that damnacanthal was able to activate mouse thymocytes and PBMC at a low concentration (0.468 microg/mL). Moreover, the production of human interleukin-2 and human interleukin-12 cytokines in the culture supernatant from damnacanthal activated lymphocytes was markedly up-regulated at 24 h and sustained until 72 h with a slight decrease with time. A positive correlation was found between the level of these two cytokines and the MTT-based proliferation assay. Based on the above results, damnacanthal can act as an immunomodulatory agent which may be very useful for maintaining a healthy immune system.
    Matched MeSH terms: Anthraquinones/isolation & purification; Anthraquinones/pharmacology*
  9. Diacerein-mediated inhibition of IL-6/IL-6R signaling induces apoptotic effects on breast cancer
    Bharti R, Dey G, Ojha PK, Rajput S, Jaganathan SK, Sen R, et al.
    Oncogene, 2016 Jul 28;35(30):3965-75.
    PMID: 26616855 DOI: 10.1038/onc.2015.466
    Interleukin-6 (IL-6) signaling network has been implicated in oncogenic transformations making it attractive target for the discovery of novel cancer therapeutics. In this study, potent antiproliferative and apoptotic effect of diacerein were observed against breast cancer. In vitro apoptosis was induced by this drug in breast cancer cells as verified by increased sub-G1 population, LIVE/DEAD assay, cell cytotoxicity and presence of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, as well as downregulation of antiapoptotic proteins Bcl-2 and Bcl-xL and upregulation of apoptotic protein Bax. In addition, apoptosis induction was found to be caspase dependent. Further molecular investigations indicated that diacerein instigated apoptosis was associated with inhibition of IL-6/IL-6R autocrine signaling axis. Suppression of STAT3, MAPK and Akt pathways were also observed as a consequence of diacerein-mediated upstream inhibition of IL-6/IL-6R. Fluorescence study and western blot analysis revealed cytosolic accumulation of STAT3 in diacerein-treated cells. The docking study showed diacerein/IL-6R interaction that was further validated by competitive binding assay and isothermal titration calorimetry. Most interestingly, it was found that diacerein considerably suppressed tumor growth in MDA-MB-231 xenograft model. The in vivo antitumor effect was correlated with decreased proliferation (Ki-67), increased apoptosis (TUNEL) and inhibition of IL-6/IL-6R-mediated STAT3, MAPK and Akt pathway in tumor remnants. Taken together, diacerein offered a novel blueprint for cancer therapy by hampering IL-6/IL-6R/STAT3/MAPK/Akt network.
    Matched MeSH terms: Anthraquinones/pharmacology*
  10. Development of biodegradable sustained-release damnacanthal nanocapsules for potential application in in-vitro breast cancer studies
    Mohd MR, Ariff TM, Mohamad N, Abdul Latif AZ, Wan Nik WMN, Mohamed A, et al.
    Pak J Pharm Sci, 2019 Sep;32(5):2155-2162.
    PMID: 31813882
    The "noni" species of Morinda citrifolia L., is using in traditional medicine in the tropical country for over 2000 years. Noni fruit has come from the Morinda citrifolia tree which is called Rubiaceae, and it is from the coffee family. It is a perennial herb whose ripe fruit has a robust butyric acid smell and flavor. Recently scientists have proven that this fruit has antioxidant and antibiotic properties in vitro. An anthraquinone, damnacanthal, is one of the constituents of Morinda citrifolia. It has been demonstrated to have anti-cancer properties. Damnacanthal has low water solubility and low bioavailability. Formulating of damnacanthal into the biodegradable nanocapsule drug delivery system may increase its bioavailability. Various formulations of damnacanthal would be developed to enable the selection of a dosage form that could offer the provision of the anti-cancer bioactive substance with suitable sustained- or controlled release properties. The efficiency of extraction of damnacanthal will be compared using both conventional and traditional method. Both the damnacanthal and an anthraquinone active compounds extracted from noni roots, are currently being studied in the context of anti-cancer study. Soon, the medical values, bioactivities and nutritional of this fruit can be assessed, especially its anti-cancer activity, this fruit extract could play an outstanding economic role in Malaysia and other tropical countries.
    Matched MeSH terms: Anthraquinones/chemistry
  11. Fulltext Aloe emodin enhances tamoxifen cytotoxicity effect on ER a-positive breast cancer cells, MCF-7, through downregulation of MEK1 and MEK2
    Amin, I.M., Sheikh Abdul Kadir, S.H., Isa, M.R., Rosdy. N.M.M.N.M., Hasani NAH
    JUMMEC, 2016;19(1):1-10.
    MyJurnal
    The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as many
    of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from
    the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breast
    cancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-
    10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of
    MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone
    or a combination of emodin and tamoxifen, at their respective IC50 concentrations and at different time points
    of 24 hours, 48 hours and 72 hours. The respective IC50s were the concentrations of aloe emodin and tamoxifen
    required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using
    trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes
    of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was
    evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of
    tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a
    rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen
    on the viability of ERa-positive-breast cancer cells.
    Matched MeSH terms: Anthraquinones
  12. Fulltext Melanosis coli
    Kew, Siang-Tong
    International e-Journal of Science, Medicine & Education, 2012;6(10):0-0.
    MyJurnal
    Melanosis coli denotes brownish discoloration of the colonic mucosa found on endoscopy
    or histopathologic examination. The condition has no specific symptom on its own. It is a fairly frequent incidental finding of colonic biopsies and resection specimens. The pigmentation is caused by apoptotic cells which are ingested by macrophages and subsequently transported into the lamina propria, where lysosomes use them to produce lipofuscin pigment, not melanin as the name suggests. Melanosis coli develops in over 70% of persons who use anthraquinone laxatives (eg cascara sagrada, aloe, senna, rhubarb, and frangula), often within 4 months of use. Long-term use is generally believed to be necessary to cause melanosis coli.The condition is widely regarded as benign and reversible, and disappearance of the pigment generally occurs within a year of stopping laxatives. Although
    often due to prolonged use of anthraquinone, melanosis can probably result from other factors or exposure to other laxatives. It has been reported as a consequence of longstanding inflammatory bowel disease. Some investigators suggested that increase in apoptosis of
    colonic mucosa by anthraquinone laxatives increased the risk of colonic cancer. Recent data, including those from large-scale retrospective, prospective and experimental studies, did not show any increased cancer risk.
    Matched MeSH terms: Anthraquinones
  13. Damnacanthal is a potent inducer of apoptosis with anticancer activity by stimulating p53 and p21 genes in MCF-7 breast cancer cells
    Aziz MY, Omar AR, Subramani T, Yeap SK, Ho WY, Ismail NH, et al.
    Oncol Lett, 2014 May;7(5):1479-1484.
    PMID: 24765160
    Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases, including cancer. Although noni has long been consumed in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In the present study, the effect of damnacanthal on MCF-7 cell growth regulation was investigated. Treatment of MCF-7 cells with damnacanthal for 72 h indicated an antiproliferative activity. The MTT method confirmed that damnacanthal inhibited the growth of MCF-7 cells at the concentration of 8.2 μg/ml for 72 h. In addition, the drug was found to induce cell cycle arrest at the G1 checkpoint in MCF-7 cells by cell cycle analysis. Damnacanthal induced apoptosis, determined by Annexin V-fluorescein isothiocyanate/propidium iodide (PI) dual-labeling, acridine-orange/PI dyeing and caspase-7 expression. Furthermore, damnacanthal-mediated apoptosis involves the sustained activation of p21, leading to the transcription of p53 and the Bax gene. Overall, the present study provided significant evidence demonstrating that p53-mediated damnacanthal induced apoptosis through the activation of p21 and caspase-7.
    Matched MeSH terms: Anthraquinones
  14. Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone
    Sulaiman SB, Keong TK, Cheng CH, Saim AB, Idrus RB
    Indian J Med Res, 2013 Jun;137(6):1093-101.
    PMID: 23852290
    Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering.
    Matched MeSH terms: Anthraquinones
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