Background: Beta-mangostin (BM) is a xanthone-type of natural compound isolated from Cratoxylum arborescens. This study aimed to examine the apoptosis mechanisms induced by BM in a murine monomyelocytic cell line (WEHI-3) in vitro and in vivo. Methods: A WEHI-3 cell line was used to evaluate the cytotoxicity of BM by MTT. AO/PI and Hoechst 33342 dyes, Annexin V, multiparametric cytotoxicity 3 by high content screening (HCS); cell cycle tests were used to estimate the features of apoptosis and BM effects. Caspase 3 and 9 activities, ROS, western blot for Bcl2, and Bax were detected to study the mechanism of apoptosis. BALB/c mice injected with WEHI-3 cells were used to assess the apoptotic effect of BM in vivo. Results: BM suppressed the growth of WEHI-3 cells at an IC50value of 14 � 3 ?g/mL in 24 h. The ROS production was increased inside the cells in the treated doses. Both caspases (9 and 3) were activated in treating WEHI-3 cells at 24, 48 and 72 h. Different signs of apoptosis were detected, such as cell membrane blebbing, DNA segmentation and changes in the asymmetry of the cell membrane. Another action by which BM could inhibit WEHI-3 cells is to restrain the cell cycle at the G1/G0 phase. In the in vivo study, BM reduced the destructive effects of leukaemia on the spleen and liver by inducing apoptosis in leukaemic cells. Conclusion: BM exerts anti-leukaemic properties in vitro and in vivo. � 2017 The Author(s).

Background: Chronic Myeloid Leukaemia (CML) is associated with the BCR-ABL1 gene, which plays a central role in the pathogenesis of CML. Thus, it is crucial to suppress the expression of BCR-ABL1 in the treatment of CML. MicroRNA is known to be a gene expression regulator and is thus a good candidate for molecularly targeted therapy for CML. Objective: This study aims to identify the microRNAs from edible plants targeting the 3’ Untranslated Region (3’UTR) of BCR-ABL1. Methods: In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target Prediction (miRTar) Server were used to identify miRNAs that have binding conformity with 3’UTR of BCR-ABL1. The MiRBase database was used to validate the species of plants expressing the miRNAs. The RNAfold web server and RNA COMPOSER were used for secondary and tertiary structure prediction, respectively. Results: In silico analyses revealed that cpa-miR8154, csi-miR3952, gma-miR4414-5p, mdm-miR482c, osa-miR1858a and osa-miR1858b show binding conformity with strong molecular interaction towards 3’UTR region of BCR-ABL1. However, only cpa-miR-8154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility. Conclusion: It is predicted that these microRNAs post-transcriptionally inhibit the BCR-ABL1 gene and thus could be a potential molecular targeted therapy for CML. However, further studies involving in vitro, in vivo and functional analyses need to be carried out to determine the ability of these miRNAs to form the basis for targeted therapy for CML. © 2020 Bentham Science Publishers.

Natural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, ?-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT assay. Results showed that AM inhibited HeLa cells viability at concentration- and time-dependent manner with IC50 value of 24.53 � 1.48 �M at 24 h. The apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy analysis. The effect of AM on cell proliferation was also studied through clonogenic assay. ROS production evaluation, flow cytometry (cell cycle) analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were conducted to determine the mechanism of cell apoptosis. This was associated with G2/M phase cell cycle arrest and elevation in ROS production. AM induced mitochondrial apoptosis which was confirmed based on the significant increase in the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP disruption and increased cell permeability, concurrent with cytochrome c release from the mitochondria to the cytosol provided evidence that AM can induce apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor effect and induced characteristic apoptogenic morphological changes on HeLa cells, which indicates the occurrence of cell death. This study reveals that AM could be a potential antitumor compound on cervical cancer in vitro and can be considered for further cervical cancer preclinical and in vivo testing. � 2017 El habbash et al.

The naturally derived flavonoids are well known to have anticarcinogenic effects. Flavonoids could be an alternative strategy for ovarian cancer treatment, due to existing platinum-based drugs are reported to develop resistance with low survival rates. Inhibition of antiapoptotic proteins, namely B-cell lymphoma (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), is the key target to stimulate apoptosis process in cancer cells. This study aimed to determine the binding interaction of five naturally derived flavonoids (biochanin A, myricetin, apigenin, galangin, and fisetin) with potential antiapoptotic target proteins (Bcl-2 and Bcl-xl). The molecular docking study was conducted using AutoDock Vina program. The binding affinity and the presence of hydrogen bonds between the flavonoids and target proteins were predicted. Our findings showed that all the flavonoids showed better binding affinity with Bcl-xl than that of Bcl-2 proteins. The highest binding affinity was recorded in fisetin–Bcl-xl protein complex (−8.8 kcal/mol). Meanwhile, the other flavonoids docked with Bcl-xl protein showed binding affinities, ranging from –8.0 to –8.6 kcal/mol. A total of four hydrogen bonds, four hydrophobic contacts, and one electrostatic interaction were detected in the docked fisetin–Bcl-xl complex, explaining its high binding affinity with Bcl-xl. The present results indicate that all flavonoids could potentially serve as Bcl-xl protein inhibitors, which would consequently lead to apoptotic process in ovarian cancers. © 2020 Wolters Kluwer Medknow Publications. All rights reserved.

Plagioneurin B belongs to acetogenin group has well-established class of compounds. Acetogenin group has attracted worldwide attention in the past few years due their biological abilities as inhibitors for several types of tumour cells. Plagioneurin B was isolated via conventional chromatography and tested for thorough mechanistic apoptosis activity on human ovarian cancer cells (CAOV-3). Its structure was also docked at several possible targets using Autodock tools software. Our findings showed that plagioneurin B successfully inhibits the growth of CAOV-3 cells at IC50 of 0.62��M. The existence of apoptotic bodies, cell membrane blebbing and chromatin condensation indicated the hallmark of apoptosis. Increase of Annexin V-FITC bound to phosphatidylserine confirmed the apoptosis induction in the cells. The apoptosis event was triggered through the extrinsic and intrinsic pathways via activation of caspases 8 and 9, respectively. Stimulation of caspase 3 and the presence of DNA ladder suggested downstream apoptotic signalling were initiated. Further confirmation of apoptosis was conducted at the molecular levels where up-regulation in Bax, as well as down-regulation of Bcl-2, Hsp-70 and survivin were observed. Plagioneurin B was also seen to arrest CAOV-3 cells cycle at the G2/M phase. Docking simulation of plagioneurin B with CD95 demonstrated that the high binding affinity and hydrogen bonds formation may explain the capability of plagioneurin B to trigger apoptosis. This study is therefore importance in finding the effective compound that may offer an alternative drug for ovarian cancer treatment. � 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Background: Various methods of isolating compounds from plants have been described previously, which include conventional or modern techniques. A preparative-HPLC (prep-HPLC) system has become one of the most convenient methods, with high purity compound as well as consumes less purification time.Objective: This study is intended to purify compounds from E. pulchrum twig extract using prep-HPLC technique and to test all compounds in several biological activities.Methods: Prior to purification using prep-HPLC, the twig extract was injected onto HPLC to develop the method through its chromatograms. The established method from HPLC was used to separate the constituents using prep-HPLC. Purified compounds were elucidated through NMR and MS methods as well as through comparison with previously reported data. Three different biological activities were then conducted on the compounds, including cytotoxicity, DPPH, FRAP, and disc diffusion assays.Results: Cinnamic acid (1) and two aporphine alkaloids (liridine (2) and lysicamine (3)) have been successfully purified and identified. These compounds were first isolated from Enicosanthellum pulchrum using prep-HPLC. Cytotoxic activity revealed that liridine (2) showed strong inhibition against WEHI-3B leukaemic cells of 8.7 �M after 24 h of treatment. In contrast, cinnamic acid (1) and lysicamine (3) exhibited strong inhibitions in antibacterial activity against Staphylococcus aureus, S. epidermidis, Bacillus cereus, Pasteurella multocida and B. subtilis with more than 15 mm of inhibition zone.Conclusion: These phytochemical findings exhibit three isolated compounds from twig extract of E. pulchrum with diverse biological potential to be developed as new agents. � 2019 Bentham Science Publishers.

Hedging method is often associated with derivatives contract. However, the application of derivatives in hedging is facing some arguments and disputes among the jumhur fuqaha (majority Islamic jurists). Therefore, various alternative methods of hedging recommendations have been given by the islamic scholars. Despite these recommendations not all of them can be applied in the current financial industry. Therefore under this study, these recommendations will be divided into 2 categories, the proposed hedging method that is difficult to be applied and the proposed hedging method that can be applied. The study found that among various tools of hedging proposed, the principle of wacd is one of the most relevant and suitable method to be adopted due to its flexiblility and easy application in hedging products. � Medwell Journals, 2014.

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potential molecular therapeutic target for various inflammatory diseases. Despite that, the role of TREM-1 during malaria pathogenesis remains obscure with present literature suggesting a link between TREM-1 with severe malaria development. Therefore, this study aims to investigate the role of TREM-1 and TREM-1 related drugs during severe malaria infection in Plasmodium berghei-infected mice model. Our findings revealed that TREM-1 concentration was significantly increased throughout the infection periods and TREM-1 was positively correlated with malaria parasitemia development. This suggests a positive involvement of TREM-1 in severe malaria development. Meanwhile, blocking of TREM-1 activation using rmTREM-1/Fc and TREM-1 clearance by mTREM-1/Ab had significantly reduced malaria parasitemia and suppressed the production of pro- inflammatory cytokines (TNF-?, IL-6 and IFN-?) and anti-inflammatory cytokine (IL-10). Furthermore, histopathological analysis of TREM-1 related drug treatments, in particular rmTREM-1/Fc showed significant improvements in the histological conditions of major organs (kidneys, spleen, lungs, liver and brain) of Plasmodium berghei-infected mice. This study showed that modulation of TREM-1 released during malaria infection produces a positive outcome on malaria infection through inhibition of pro-inflammatory cytokines secretion and alleviation of histopathological conditions of affected organs. Nevertheless, further investigation on its optimal dosage and dose dependant study should be carried out to maximise its full potential as immunomodulatory or as an adjuvant in line with current antimalarial agents. � 2018, Indian Society for Parasitology.