Displaying publications 81 - 100 of 6751 in total

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  1. Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F
    Bioorg Chem, 2017 02;70:184-191.
    PMID: 28043716 DOI: 10.1016/j.bioorg.2016.12.009
    Thiourea derivatives having benzimidazole 1-17 have been synthesized, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for α-glucosidase inhibition. Identification of potential α-glucosidase inhibitors were done by in vitro screening of 17 thiourea bearing benzimidazole derivatives using Baker's yeast α-glucosidase enzyme. Compounds 1-17 exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 35.83±0.66 and 297.99±1.20μM which are more better than the standard acarbose (IC50=774.5±1.94μM). Compound 10 and 14 showed significant inhibitory effects with IC50 value 50.57±0.81 and 35.83±0.66μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
    Matched MeSH terms: Benzimidazoles/pharmacology*; Thiourea/pharmacology*; Glycoside Hydrolase Inhibitors/pharmacology*
  2. Zawawi MS, Dharmapatni AA, Cantley MD, McHugh KP, Haynes DR, Crotti TN
    Biochem Biophys Res Commun, 2012 Oct 19;427(2):404-9.
    PMID: 23000414 DOI: 10.1016/j.bbrc.2012.09.077
    Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (β3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment significantly (p<0.05) reduced the expression of NFATc1, CathK, OSCAR, FcRγ, TREM2 and DAP12 during the terminal stage of osteoclast formation. VIVIT treatment significantly (p<0.05) decreased CathK, OSCAR, FcRγ, and AnnVIII, gene expression. This data suggest FK506 and VIVIT act differently in targeting the calcineurin-NFAT signalling cascade to suppress key mediators of the ITAM pathway during late stage osteoclast differentiation and this is associated with a reduction in both osteoclast differentiation and activity.
    Matched MeSH terms: Oligopeptides/pharmacology; Tacrolimus/pharmacology
  3. Zaw MT, Lin Z, Emran NA
    J Microbiol Immunol Infect, 2020 Oct;53(5):676-681.
    PMID: 31563454 DOI: 10.1016/j.jmii.2019.07.006
    The mortality caused by Plasmodium falciparum was reduced by Artemisinin (ART) and ART combination therapy (ACT). However, Artemisinin resistance (ART-R) emerge during 2008 in Cambodia and spread to Greater Mekong Subregion (GMS). ART-R was confirmed not to spread to India, a gateway to whole Africa. The whole genome sequencing approach of P. falciparum assumed the k13 gene encoded Kelch protein was discovered to be associated with ART-R. Of the single nucleotide polymorphisms (SNPs) of k13 gene, C580Y mutant was commonly dominant in Cambodia, Myanmar, Thailand, Laos and Vietnam and assumed to be one of strong molecular markers for ART-R in P. falciparum isolates in GMS. Literatures published between 2017 and 2018 were reviewed in this work. F446I is observed to be doubtful molecular marker as ART-R marker. Transgenic experiment showed that parasite with F446I mutation displayed prolonged clearance in respond to ART while C580Y was applied as positive control mutant. Furthermore, study of C580Y allele in four countries Cambodia, Thailand, Laos resulted in single origin whereas the parasite with this allele showed multi-origin in three Provinces of Vietnam. As artemisinin was short acting drug, the role of long acting partner drug was studied by using transgenic C580Y mutant and C580 to leave recrudescent P. falciparum. Recently, there was treatment failure with ACT in some countries in GMS. In this review, the importance of C580Y mutation in the study of ART-R was discussed.
    Matched MeSH terms: Artemisinins/pharmacology*
  4. Zaw MT, Emran NA, Lin Z
    J Microbiol Immunol Infect, 2018 Apr;51(2):159-165.
    PMID: 28711439 DOI: 10.1016/j.jmii.2017.06.009
    BACKGROUND: In the fight against malaria caused by Plasmodium falciparum, the successes achieved by artemisinin were endangered by resistance of the parasites to the drug. Whole genome sequencing approach on artemisinin resistant parasite line discovered k13 gene associated with drug resistance. In vitro and in vivo studies indicated mutations in the k13 gene were linked to the artemisinin resistance.

    METHODOLOGY: The literatures published after April, 2015 up to December, 2016 on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum and relevant literatures were comprehensively reviewed.

    RESULTS: To date, 13 non-synonymous mutations of k13 gene have been observed to have slow parasite clearance. Worldwide mapping of k13 mutant alleles have shown mutants associated with artemisinin resistance were confined to southeast Asia and China and did not invade to African countries. Although in vitro ring stage survival assay of 0-3 h was a recently developed assay, it was useful for rapid detection of artemisinin resistance associated k13 allelic marker in the parasite. Recently, dissemination of k13 mutant alleles was recommended to be investigated by identity of haplotypes. Significant characteristics of well described alleles in the reports were mentioned in this review for the benefit of future studies.

    CONCLUSION: According to the updates in the review, it can be concluded artemisinin resistance does not disseminate to India and African countries within short period whereas regular tracking of these mutants is necessary.

    Matched MeSH terms: Antimalarials/pharmacology*; Artemisinins/pharmacology*
  5. Zaulkffali AS, Md Razip NN, Syed Alwi SS, Abd Jalil A, Abd Mutalib MS, Gopalsamy B, et al.
    Nutrients, 2019 Oct 19;11(10).
    PMID: 31635074 DOI: 10.3390/nu11102525
    This study investigated the effects of vitamins D and E on an insulin-resistant model and hypothesized that this treatment would reverse the effects of Alzheimer's disease (AD) and improves insulin signalling. An insulin-resistant model was induced in SK-N-SH neuronal cells with a treatment of 250 nM insulin and re-challenged with 100 nM at two different incubation time (16 h and 24 h). The effects of vitamin D (10 and 20 ng/mL), vitamin E in the form of tocotrienol-rich fraction (TRF) (200 ng/mL) and the combination of vitamins D and E on insulin signalling markers (IR, PI3K, GLUT3, GLUT4, and p-AKT), glucose uptake and AD markers (GSK3β and TAU) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The results demonstrated an improvement of the insulin signalling pathway upon treatment with vitamin D alone, with significant increases in IR, PI3K, GLUT3, GLUT4 expression levels, as well as AKT phosphorylation and glucose uptake, while GSK3β and TAU expression levels was decreased significantly. On the contrary, vitamin E alone, increased p-AKT, reduced the ROS as well as GSK3β and TAU but had no effect on the insulin signalling expression levels. The combination of vitamins D and E only showed significant increase in GLUT4, p-AKT, reduced ROS as well as GSK3β and TAU. Thus, the universal role of vitamin D, E alone and in combinations could be the potential nutritional agents in restoring the sensitivity of neuronal cells towards insulin and delaying the pathophysiological progression of AD.
    Matched MeSH terms: Vitamin D/pharmacology*; Vitamin E/pharmacology*
  6. Zarzour RHA, Alshawsh MA, Asif M, Al-Mansoub MA, Mohamed Z, Ahmad M, et al.
    Nutrients, 2018 Aug 09;10(8).
    PMID: 30096951 DOI: 10.3390/nu10081057
    The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.
    Matched MeSH terms: Plant Extracts/pharmacology*; Angiogenesis Inhibitors/pharmacology*
  7. Zaroog MS, Abdul Kadir H, Tayyab S
    ScientificWorldJournal, 2013;2013:570859.
    PMID: 24163624 DOI: 10.1155/2013/570859
    Different spectral probes were employed to study the stabilizing effect of various polyols, such as, ethylene glycol (EG), glycerol (GLY), glucose (GLC) and trehalose (TRE) on the native (N), the acid-denatured (AD) and the thermal-denatured (TD) states of Aspergillus niger glucoamylase (GA). Polyols induced both secondary and tertiary structural changes in the AD state of enzyme as reflected from altered circular dichroism (CD), tryptophan (Trp), and 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence characteristics. Thermodynamic analysis of the thermal denaturation curve of native GA suggested significant increase in enzyme stability in the presence of GLC, TRE, and GLY (in decreasing order) while EG destabilized it. Furthermore, CD and fluorescence characteristics of the TD state at 71°C in the presence of polyols showed greater effectiveness of both GLC and TRE in inducing native-like secondary and tertiary structures compared to GLY and EG.
    Matched MeSH terms: Glycerol/pharmacology; Polymers/pharmacology*; Trehalose/pharmacology; Ethylene Glycol/pharmacology
  8. Zarkasi KA, Jen-Kit T, Jubri Z
    Mini Rev Med Chem, 2019;19(17):1407-1426.
    PMID: 30706809 DOI: 10.2174/1389557519666190130164334
    Myocardial infarction is a major cause of deaths globally. Modulation of several molecular mechanisms occurs during the initial stages of myocardial ischemia prior to permanent cardiac tissue damage, which involves both pathogenic as well as survival pathways in the cardiomyocyte. Currently, there is increasing evidence regarding the cardioprotective role of vitamin E in alleviating the disease. This fat-soluble vitamin does not only act as a powerful antioxidant; but it also has the ability to regulate several intracellular signalling pathways including HIF-1, PPAR-γ, Nrf-2, and NF-κB that influence the expression of a number of genes and their protein products. Essentially, it inhibits the molecular progression of tissue damage and preserves myocardial tissue viability. This review aims to summarize the molecular understanding of the cardiomodulation in myocardial infarction as well as the mechanism of vitamin E protection.
    Matched MeSH terms: Antioxidants/pharmacology; Vitamin E/pharmacology*; Protective Agents/pharmacology*
  9. Zarida H, Wan Zurinah WN, Zanariah J, Michael LK, Khalid BA
    Exp. Toxicol. Pathol., 1994 Mar;46(1):31-6.
    PMID: 7916223
    The effect of ovariectomy and sex hormone/s replacement in female rats was investigated by the determination of the tumour marker enzymes gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP). This was compared to ovariectomized rats receiving sex hormone replacement and treated with carcinogen. Ovariectomy significantly increased the activity of plasma GGT. Plasma and microsomal ALP and microsomal GGT were unchanged. When replacements of estrogen (E), or progesterone (Prog), or combinations of both estrogen and progesterone were given to ovariectomized rats, the activity of plasma GGT was brought to the level of normal intact females. Treatment with carcinogen increased the PGGT activities in intact rats. In ovariectomized rats receiving carcinogen, the PGGT activities were significantly lower than in intact females and rats receiving both hormone replacement and carcinogen (p < 0.01). Carcinogen treatment in case of estrogen or progesterone replacement, either individually or in combination, showed GGT activities comparable to intact females receiving carcinogen. Both plasma and microsomal ALP were not affected by carcinogen administration. These results showed that ovariectomy reduced the severity of hepatocarcinogenesis while sex hormone replacement worsened the process.
    Matched MeSH terms: Carcinogens/pharmacology*; Estradiol/pharmacology*; Progesterone/pharmacology*
  10. Zargar M, Hamid AA, Bakar FA, Shamsudin MN, Shameli K, Jahanshiri F, et al.
    Molecules, 2011 Aug 08;16(8):6667-76.
    PMID: 25134770 DOI: 10.3390/molecules16086667
    Different biological methods are gaining recognition for the production of silver nanoparticles (Ag-NPs) due to their multiple applications. One of the most important applications of Ag-NPs is their use as an anti-bacterial agent. The use of plants in the synthesis of nanoparticles emerges as a cost effective and eco-friendly approach. In this study the biosynthesis of silver nanoparticles using Vitex negundo L. extract and its antimicrobial properties has been reported. The resulting silver particles are characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD) and UV-Visible (UV-Vis) spectroscopic techniques. The TEM study showed the formation of silver nanoparticles in the 10-30 nm range and average 18.2 nm in size. The XRD study showed that the particles are crystalline in nature, with a face centered cubic (fcc) structure. The silver nanoparticles showed the antimicrobial activity against Gram positive and Gram negative bacteria. Vitex negundo L. was found to display strong potential for the synthesis of silver nanoparticles as antimicrobial agents by rapid reduction of silver ions (Ag+ to Ag0).
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology*; Silver/pharmacology*
  11. Zarei M, Ghanbari R, Tajabadi N, Abdul-Hamid A, Bakar FA, Saari N
    J Food Sci, 2016 Feb;81(2):C341-7.
    PMID: 26720491 DOI: 10.1111/1750-3841.13200
    Palm kernel cake protein was hydrolyzed with different proteases namely papain, bromelain, subtilisin, flavourzyme, trypsin, chymotrypsin, and pepsin to generate different protein hydrolysates. Peptide content and iron-chelating activity of each hydrolysate were evaluated using O-phthaldialdehyde-based spectrophotometric method and ferrozine-based colorimetric assay, respectively. The results revealed a positive correlation between peptide contents and iron-chelating activities of the protein hydrolysates. Protein hydrolysate generated by papain exhibited the highest peptide content of 10.5 mM and highest iron-chelating activity of 64.8% compared with the other hydrolysates. Profiling of the papain-generated hydrolysate by reverse phase high performance liquid chromatography fractionation indicated a direct association between peptide content and iron-chelating activity in most of the fractions. Further fractionation using isoelectric focusing also revealed that protein hydrolysate with basic and neutral isoelectric point (pI) had the highest iron-chelating activity, although a few fractions in the acidic range also exhibited good metal chelating potential. After identification and synthesis of papain-generated peptides, GGIF and YLLLK showed among the highest iron-chelating activities of 56% and 53%, whereas their IC50 were 1.4 and 0.2 μM, respectively.
    Matched MeSH terms: Iron Chelating Agents/pharmacology*; Peptides/pharmacology*; Protein Hydrolysates/pharmacology*
  12. Zarei M, Abidin NBZ, Auwal SM, Chay SY, Haiyee ZA, Sikin AM, et al.
    Biomolecules, 2019 10 04;9(10).
    PMID: 31590308 DOI: 10.3390/biom9100569
    Three novel peptide sequences identified from palm kernel cake (PKC) generated protein hydrolysate including YLLLK, WAFS and GVQEGAGHYALL were used for stability study against angiotensin-converting enzyme (ACE), ACE-inhibition kinetics and molecular docking studies. Results showed that the peptides were degraded at different cleavage degrees of 94%, 67% and 97% for YLLLK, WAFS and GVQEGAGHYALL, respectively, after 3 h of incubation with ACE. YLLLK was found to be the least stable (decreased ACE-inhibitory activity) compared to WAFS and GVQEGAGHYALL (increased ACE-inhibitory activity). YLLLK showed the lowest Ki (1.51 mM) in inhibition kinetics study when compared to WAFS and GVQEGAGHYALL with Ki of 2 mM and 3.18 mM, respectively. In addition, ACE revealed the lowest Kmapp and Vmaxapp and higher catalytic efficiency (CE) in the presence of YLLLK at different concentrations, implying that the enzyme catalysis decreased and hence the inhibition mode increased. Furthermore, YLLLK showed the lowest docking score of -8.224 and seven interactions with tACE, while peptide GVQEGAGHYALL showed the higher docking score of -7.006 and five interactions with tACE.
    Matched MeSH terms: Peptide Fragments/pharmacology*
  13. Zare-Zardini H, Taheri-Kafrani A, Amiri A, Bordbar AK
    Sci Rep, 2018 01 12;8(1):586.
    PMID: 29330486 DOI: 10.1038/s41598-017-18938-y
    In this study, Rh2-treated graphene oxide (GO-Rh2), lysine-treated highly porous graphene (Gr-Lys), arginine-treated Gr (Gr-Arg), Rh2-treated Gr-Lys (Gr-Lys-Rh2) and Rh2-treated Gr-Arg (Gr-Arg-Rh2) were synthesized. MTT assay was used for evaluation of cytotoxicity of samples on ovarian cancer (OVCAR3), breast cancer (MDA-MB), Human melanoma (A375) and human mesenchymal stem cells (MSCs) cell lines. The percentage of apoptotic cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The hemolysis and blood coagulation activity of nanostructures were performed. Interestingly, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2 were more active against cancer cell lines in comparison with their cytotoxic activity against normal cell lines (MSCs) with IC50 values higher than 100 μg/ml. The results of TUNEL assay indicates a significant increase in the rates of TUNEL positive cells by increasing the concentrations of nanomaterials. Results were also shown that aggregation and changes of RBCs morphology were occurred in the presence of GO, GO-Rh2, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2. Note that all the samples had effect on blood coagulation system, especially on PTT. All nanostrucure act as antitumor drug so that binding of drugs to a nostructures is irresolvable and the whole structure enter to the cell as a drug.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Arginine/pharmacology*; Lysine/pharmacology*; Ginsenosides/pharmacology*
  14. Zanul Abidin Z, Mohd Salleh N, Himratul-Aznita WH, Ahmad SF, Lim GS, Raja Mohd N, et al.
    PeerJ, 2023;11:e15750.
    PMID: 37601266 DOI: 10.7717/peerj.15750
    BACKGROUND: The study's objective is to assess the adherence of C. albicans in different types of denture polymers and the effectiveness of eugenol and commercialized denture cleansers in the removal of C. albicans. Three types of denture base polymers (Lucitone® 199 (High-Impact PMMA), Impact® (conventional PMMA) and Eclipse® (UDMA)) and two hard denture reline materials (Kooliner® and Tokuyama® Rebase II Fast) were used in this study.

    METHODS: Three hundred samples were prepared (6 × 2 mm disc shape) and divided into five groups of denture polymers (n = 60) and further subjected into five treatment groups (Polident®, Steradent, distilled water, eugenol 5-minutes, and eugenol 10-min). Three samples were extracted from each treatment group for baseline data (n = 12). Baseline data were used to calculate the initial number of C. albicans adherence. A 0.5 ml immersion solution from each specimen was cultured on YPD agar and incubated for 48 h at 37 °C. Visible colonies were counted using a colony counter machine (ROCKER Galaxy 230).

    RESULTS: The result showed that the denture base polymer significantly affected the initial adherence (p = 0.007). The removal of C. albicans was also considerably affected by the denture base polymers and denture cleansers (p 

    Matched MeSH terms: Denture Cleansers/pharmacology; Eugenol/pharmacology; Polymers/pharmacology
  15. Zandi K, Lani R, Wong PF, Teoh BT, Sam SS, Johari J, et al.
    Molecules, 2012;17(3):2437-45.
    PMID: 22374315 DOI: 10.3390/molecules17032437
    This study investigates the effects of 2-phenyl-1-benzopyran-4-one (flavone) on DENV-2 infectivity in Vero cells. Virus adsorption and attachment and intracellular virus replication were investigated using a foci forming unit assay (FFUA) and quantitative RT-PCR, respectively. Addition of flavone (100 μg/mL) significantly increased the number of DENV-2 foci by 35.66% ± 1.52 and 49.66% ± 2.51 when added during and after virus adsorption to the Vero cells, respectively. The average foci size after 4 days of infection increased by 33% ± 2.11 and 89% ± 2.13. The DENV-2 specific RNA copy number in the flavone-treated infected cells increased by 6.41- and 23.1-fold when compared to the mock-treated infected cells. Flavone (100 μg/mL) did not promote or inhibit Vero cell proliferation. The CC₅₀ value of flavone against Vero cells was 446 µg/mL. These results suggest that flavone might enhance dengue virus replication by acting antagonistically towards flavonoids known to inhibit dengue virus replication.
    Matched MeSH terms: Flavones/pharmacology*
  16. Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa MR, Abubakar S
    PMID: 23140177 DOI: 10.1186/1472-6882-12-214
    Dengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV) replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits.
    Matched MeSH terms: Antiviral Agents/pharmacology; Plant Extracts/pharmacology; Flavanones/pharmacology
  17. Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa MR, Abubakar S
    Virol J, 2011;8:560.
    PMID: 22201648 DOI: 10.1186/1743-422X-8-560
    Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for each compound.
    Matched MeSH terms: Antiviral Agents/pharmacology*; Flavonoids/pharmacology*; Hesperidin/pharmacology; Quercetin/pharmacology; Flavanones/pharmacology
  18. Zandi K
    Methods Mol Biol, 2016;1426:255-62.
    PMID: 27233278 DOI: 10.1007/978-1-4939-3618-2_23
    Screening of viral inhibitors through induction of cytopathic effects (CPE) by conventional method has been applied for various viruses including Chikungunya virus (CHIKV), a significant arbovirus. However, it does not provide the information about cytopathic effect from the beginning and throughout the course of virus replication. Conventionally, most of the approaches are constructed on laborious end-point assays which are not capable for detecting minute and rapid changes in cellular morphology. Therefore, we developed a label-free and dynamical method for monitoring the cellular features that comprises cell attachment, proliferation, and viral cytopathogenicity, known as the xCELLigence real-time cell analysis (RTCA). In this chapter, we provide a RTCA protocol for quantitative analysis of CHIKV replication using an infected Vero cell line treated with ribavirin as an in vitro model.
    Matched MeSH terms: Antiviral Agents/pharmacology*; Ribavirin/pharmacology*
  19. Zandi K, Bassit L, Amblard F, Cox BD, Hassandarvish P, Moghaddam E, et al.
    PMID: 31061163 DOI: 10.1128/AAC.00397-19
    Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.
    Matched MeSH terms: Antiviral Agents/pharmacology*; Nucleosides/pharmacology
  20. Zandi K, Lim TH, Rahim NA, Shu MH, Teoh BT, Sam SS, et al.
    BMC Complement Altern Med, 2013 Apr 29;13:91.
    PMID: 23627436 DOI: 10.1186/1472-6882-13-91
    BACKGROUND: Scutellaria baicalensis (S. baicalensis) is one of the traditional Chinese medicinal herbs that have been shown to possess many health benefits. In the present study, we evaluated the in vitro antiviral activity of aqueous extract of the roots of S. baicalensis against all the four dengue virus (DENV) serotypes.

    METHODS: Aqueous extract of S. baicalensis was prepared by microwave energy steam evaporation method (MEGHE™), and the anti-dengue virus replication activity was evaluated using the foci forming unit reduction assay (FFURA) in Vero cells. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the actual dengue virus RNA copy number. The presence of baicalein, a flavonoid known to inhibit dengue virus replication was determined by mass spectrometry.

    RESULTS: The IC(50) values for the S. baicalensis extract on Vero cells following DENV adsorption ranged from 86.59 to 95.19 μg/mL for the different DENV serotypes. The IC(50) values decreased to 56.02 to 77.41 μg/mL when cells were treated with the extract at the time of virus adsorption for the different DENV serotypes. The extract showed potent direct virucidal activity against extracellular infectious virus particles with IC(50) that ranged from 74.33 to 95.83 μg/mL for all DENV serotypes. Weak prophylactic effects with IC(50) values that ranged from 269.9 to 369.8 μg/mL were noticed when the cells were pre-treated 2 hours prior to virus inoculation. The concentration of baicalein in the S. baicalensis extract was ~1% (1.03 μg/gm dried extract).

    CONCLUSIONS: Our study demonstrates the in vitro anti-dengue virus replication property of S. baicalensis against all the four DENV serotypes investigated. The extract reduced DENV infectivity and replication in Vero cells. The extract was rich in baicalein, and could be considered for potential development of anti-DENV therapeutics.

    Matched MeSH terms: Antiviral Agents/pharmacology*; Plant Extracts/pharmacology*
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