Publications by authors named "Leila Hosseinzadeh"

44 Publications

Flexible electrospun nanofibrous film integrated with fluorescent carbon dots for smartphone-based detection and cellular imaging application.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 11;260:119944. Epub 2021 May 11.

Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran.

The dose of administered chemotherapy drugs is crucial to determine due to the potential for efficient or adverse outcomes for cancer patients. To date, no user-friendly and low-cost method of doxorubicin (DOX) detection using nontoxic and biodegradable materials has been reported. For this reason, in this work, we have developed for the first time a nanofiber-based sensing platform for sensitive and on-site DOX assay in just 10 min. This is obtained thanks to printable, porosity and embeddability features of electrospun nanofibrous films (ENFFs) combined with nitrogen and sulfur co-doped carbon dots (NS-CDs) as sensing probes. The assay was done by just pipetting analyte on the hydrophilic spots of the fabricated photoluminescence water-stable ENFFs where the color intensity was being darkened. DOX quenched NS-CDs fluorescence onto ENFFs through inner filter effect. The developed sensor was either coupled with smartphone technology to provide miniaturized, portable and easy-to-use device or an ordinary spectrofluorimeter for solid-state sensing applications (detection limit of 5.4 nM). Moreover, applicability of the designed sensor was evaluated in human serum with satisfactory recoveries. It is more interesting that the fabricated NS-CDs/ENF scaffolds have a high potential to detect the intracellular DOX to enhance cell proliferation leading to be considered as a multimodal tool in biomedical research and clinical diagnostics.
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http://dx.doi.org/10.1016/j.saa.2021.119944DOI Listing
November 2021

Synthesis and in vitro quantification of amyloid fibrils by barbituric and thiobarbituric acid-based chromene derivatives.

Biophys Chem 2021 02 15;269:106522. Epub 2020 Dec 15.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Neurodegenerative disease is caused by the abnormal build-up of proteins in and around cells called amyloid. The amyloid fibril formation and its mechanism have been investigated with various techniques, including dye-binding assay. Thioflavin T (ThT) has been one of the most widely used dyes for quantifying amyloid deposits, but ThT has a weak fluorescence signal especially at low concentration of amyloid fibrils, low lipophilicity and positive charge that makes it unable to cross the blood-brain barrier (BBB) to detect amyloid fibrils in vivo. Hence, there is a strong motivation for designing and developing the new compounds for in vitro amyloid quantification and in vivo amyloid imaging. The need for new probes to detect amyloid fibrils, especially within the cell, is highlighted by the fact that an accurate understanding of the molecular details of amyloid fibril formation is required to design and develop strategies for controlling the amyloid formation, and this needs more reliable probes for amyloid identification. In this work, we synthesized and applied barbituric and thiobarbituric acid-based chromene derivatives, as new fluorescent dyes to quantitatively detect the amyloid fibrils of bovine serum albumin (BSA) and human insulin in comparison with native soluble proteins or amorphous aggregation. Our results showed that among the 14 synthesized compounds, five compounds 4a, 4h, 4j, 4k, and 4l could selectively and specifically bind to amyloid fibrils while other compounds demonstrated a low-affinity binding. Furthermore, according to the cell viability experiment, compounds 4a, 4j and 4l at low concentration of compounds are not toxic, especially compound 4j which could be used as a suitable candidate for in vivo study. Further studies are needed to determine all the properties of compounds, especially in vivo experiments.
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http://dx.doi.org/10.1016/j.bpc.2020.106522DOI Listing
February 2021

Preparation, Characterization and In Vitro Biological Evaluation of Novel Curcumin Derivatives as Cytotoxic and Apoptosis-Inducing Agents.

Anticancer Agents Med Chem 2021 ;21(10):1309-1322

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Curcumin is a natural polyphenol and lead compound of the rhizomes of curcuma longa and it has been widely used for pharmacological activities.

Objective: In this study, a series of novel derivatives of curcumin, with this group linked to a 2-amino-4- phenylpyran-3-carbonitrile system, have been synthesized and tested for their antitumor activities in vitro against a panel of three human cancer cell lines (MCF-7, A2780, and U-87MG).

Methods: The in vitro cytotoxic activity of the synthesized compounds was tested on three cancer cell lines (MCF-7, A2780, and U-87MG) using MTT colorimetric assay. Meanwhile, the ability of the active compounds to induce apoptosis in cancer cells was investigated by examination of caspase-3 and caspase-9 and mitochondrial membrane potential assay.

Results: Under relatively mild conditions in ethanol, the reaction of a series of substrates afforded the corresponding derivatives of curcumin mostly in good yields (13 analogues, 48-94% yields). Bioassay results indicated that compounds L6 (para-Bromo), L9 (para-Nitro) and L12 (meta-Methoxy) were the most active members in this study demonstrating potent activities against A2780 cancer cells and experimental results of fluorescent staining and flow cytometry analysis revealed that L6 and L9 could induce apoptosis in A2780 cells with apoptosis ratios of about 40% and 46%, respectively at 24h of treatment at 15.35μM and 23μM in A2780 cells. On the other hand, they could increase the caspase-3 activity slightly (10%), while having no significant impact on the activities of caspase-9.

Conclusion: Those two derivatives could be considered as useful templates for future development to obtain more potent antitumor agents.
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http://dx.doi.org/10.2174/1871520620666201002111205DOI Listing
January 2021

Spherical Gold Nanoparticles: Small Interfering RNA Delivery in Regulation of the Tumor Necrosis Factor-Alpha Gene Expression.

J Interferon Cytokine Res 2020 10 28;40(10):490-496. Epub 2020 Aug 28.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Proinflammatory cytokines are signaling molecules that are expelled from immune cells like macrophages and other types of cells. Tumor necrosis factor-alpha (TNF-α) is overexpressed during inflammation caused by inflammatory diseases. Therefore, the regulation of TNF-α has a key role in inflammation. The use and target delivery of small interfering RNAs (siRNAs) provide many effectual treatment benefits in the regulation of gene expression in cells. In this study, we used siRNA nanoparticle conjugates in the regulation of gene expression and inflammation. We first prepared safe fusion ribonucleic acid interference carrier, spherical nucleic acid nanoparticle conjugates (SNA-NCs), to enhance the perforation of siRNA into the macrophages and their ability to target TNF-α gene regulation. Furthermore, the suppression of the TNF-α gene was monitored after curing macrophages by SNA-NCs. Gene expression was carried out by real-time polymerase chain reaction in cells and the levels of TNF-α were investigated by the enzyme-linked immunosorbent assay (ELISA) method. This study indicated that the SNA-NCs were safe and very stable. TNF-α siRNA could significantly regulate gene expression in cells to form SNA-NCs. The results indicated that TNF-α gene expression downregulated to 93.40% ± 1.45%, 66.06% ± 0.95%, and 35.76% ± 1.09% in the presence of 0.1, 1, and 10 nM siRNA, respectively. The proliferation of macrophages and subsequently expression of TNF-α were significant for the formation of inflammation. These findings showed that the use of SNA-NC siRNA might ameliorate the inflammatory disease by suppression of gene expression and functional activity of macrophage generation.
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http://dx.doi.org/10.1089/jir.2020.0090DOI Listing
October 2020

Evaluation of the cytotoxic and apoptogenic effects of cinnamaldehyde on U87MG cells alone and in combination with doxorubicin.

Res Pharm Sci 2020 Feb 20;15(1):26-35. Epub 2020 Feb 20.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

Background And Purpose: In the present study, we tried for the first time to examine whether cinnamaldehyde (CA), with herbal nature, can be co-administrated with doxorubicin (DOX, as an anticancer drug) toward U87MG glioblastoma cells to potentiate its cytotoxic effect and overcome or reduce its side effects.

Experimental Approach: The cytotoxic effect of DOX and CA, either individually or in combination, were evaluated on U87MG cells using the MTT method. The mechanism of action was studied by investigating the mode of cell death using caspase-3 and 9 activations, mitochondrial membrane potential (MMP) as well as sub G1 analysis. The expression of apoptosis- related genes (Bcl-2 and Bax) was also examined.

Findings / Results: Cellular toxicity assay revealed that CA and DOX can potentially reduce the viability of U87MG cells with IC50 at 11.6 and 5 μg/mL, respectively. Exposure with the combination of CA and DOX significantly increased cytotoxic effect of DOX on U87MG cells. The results of SUBG1, MMP, and also caspase-3 and -9 activity assays, in association with the results corresponding to the Bax and Bcl-2 gene expressions, altogether revealed that CA can induce apoptosis on U87MG cells. Moreover, apoptogenic effects of DOX were found to be potentiated by CA.

Conclusion And Implications: The results of this study revealed the promising cytotoxic and apoptogenic role of CA on U87MG cells. Additionally, our findings demonstrated that CA is able to enhance the apoptosis induced by DOX on human glioblastoma cells. Collectively, these data suggested that co-exposure of CA and DOX could be effective for treatment of glioblastoma, but further and clinical studies are still needed to prove these results.
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http://dx.doi.org/10.4103/1735-5362.278712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053293PMC
February 2020

Ratiometric bioassay and visualization of dopamine β-hydroxylase in brain cells utilizing a nanohybrid fluorescence probe.

Anal Chim Acta 2020 Apr 29;1105:187-196. Epub 2020 Jan 29.

Department of Biotechnology, Bu-Ali Sina University, Hamedan, Iran.

Dopamine β-hydroxylase (DBH) is involved in various neuronal transmission processes in the brain. Due to the severe diseases caused by abnormity levels of such important enzyme in human serum, sensitive and rapid detection of DBH at early stages is crucial, particularly for clinical analysis. Herein, we developed optical sensors for DBH that include the following: (i) a ratiometric fluorescence sensor that hybridizes the bovine serum albumin (BSA)-gold nanoclusters (BSA-AuNCs) and nitrogen doped carbon dots (N-CDs). The sensor proved to be highly selective and sensitive, achieving a linear range of 0.02-0.16 μg mL and a limit of detection of 4.0 ng mL. In the presence of DBH, the fluorescence intensity of BSA-AuNCs (λ = 615 nm) was remarkably quenched by DBH serving as a reporter signal, whereas the N-CDs fluorescence intensity at 440 nm was almost kept unchanged serving as a reference signal. The developed ratiometric sensor is capable of demonstrating a color change from pink to violet and blue with a gradual increase in DBH concentration, which is discernible by the naked-eye. A test strip is prepared for semi-quantitative assay and convenient use. Intriguingly, by taking advantage of the inter-AuNCs aggregation in the presence of DBH, (ii) a resonance light scattering (RLS) sensor was also developed based on the nanohybrid probe (detection limit 95 ng mL). Fluorescence imaging in PC12 cell lines demonstrated that the BSA-AuNCs could be utilized in visualization assay towards intracellular DBH. Additionally, the sensors were tested in a real matrix by spiking serum samples with satisfactory recoveries.
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http://dx.doi.org/10.1016/j.aca.2020.01.046DOI Listing
April 2020

TSGA10 Over Expression Decreases Metastasic and Metabolic Activity by Inhibiting HIF-1 in Breast Cancer Cells.

Arch Med Res 2020 01 18;51(1):41-53. Epub 2020 Feb 18.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical sciences, Kermanshah, Iran; Department of Molecular Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background And Aims: HIF-1 is an important factor that play critical roles in metabolic and metastasis activity of cancer cells. HIF-1 activity can have regulated by TSGA10. Although decreased metastatic activity of cancer cells through TSGA10 inhibitory effect on HIF-1 have already been demonstrated, changes in cancer metabolism and its impact on metastasis in breast cancer is still not determined. So, we aimed to investigate TSGA10 overexpression effect on breast cancer metabolism as well as metastasis.

Methods: TSGA10 vector was designed and stable transfected into MCF-7 cells. The efficiency of transfection was assessed by Real-time PCR and western blot. After HIF-1 induction at high and low glucose conditions, cell proliferation, cell cycle profile, metabolic and metastasis activity of cells were assessed. Furthermore, biomarker expressions of ER, PR, HER2, Ki67 and E-cadherin in cancer cells were measured.

Results: Our results showed decrease of cell proliferation and cell cycle arrest in G2/M phase. Reduce expression of GLUT1, lactate production and reactive oxygen species (ROS) below their basal level indicated decreased metabolic activity. Furthermore, metastatic activity reduction was shown by decrease expression of different involve genes in metastasis, protelytic activity of MMOLP-2/9, carbonic anhydrase (CA) IX activity and increase of wound closure. Moreover, except for E-cadherin, expression of ER, PR, HER2 and Ki67 was declined in cells.

Conclusion: Our findings indicated that TSGA10 overexpression could decrease the metastatic and metabolic activity of cancer cells through its inhibitory effect on HIF-1 activity. Therefore, TSGA10 could be considered in the research for therapeutic candidates in cancer.
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http://dx.doi.org/10.1016/j.arcmed.2019.12.002DOI Listing
January 2020

Application of dextran-coated iron oxide nanoparticles in enhancing the radiosensitivity of cancerous cells in radiotherapy with high-energy electron beams.

J Cancer Res Ther 2019 Oct-Dec;15(6):1352-1358

Department of Medical Physics, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Purpose: Nowadays, cancer is one of the most important causes of morbidity and mortality in the world. The ideal aim of radiotherapy is delivering a lethal radiation dose to tumor cells while minimizing radiation exposure to healthy tissues around the tumor. One way to increase the dose in the tumor cells is the use of high-atomic number nanoparticles as radiosensitizer agents in these cells. The aim of this in vitro study was investigating the radiosensitization enhancement potential of the dextran-coated iron oxide nanoparticles (IONPs) on HeLa and MCF-7 cell lines in irradiations with high-energy electron beams.

Materials And Methods: In this in vitro study, the cytotoxicity level of dextran-coated IONPs at different concentrations (10, 40, and 80 μg/ml) was assessed on HeLa and MCF-7 cell lines. To evaluate the radiosensitivity effect, the nanoparticles were incubated with the cells at different concentrations for 24 h and afterward irradiated with different doses (0, 2, 4, 6, and 8 Gy) of 6 and 12 MeV electron beams. The cells survival fractions were obtained by the methylthiazoletetrazolium assay.

Results: Toxicity results of the nanoparticles at 10 and 40 μg/ml concentrations showed no significant cytotoxicity effect. The cells survival rates in groups receiving radiation in the absence and presence of IONPs showed a significant difference. The radiosensitivity enhancement induced by the nanoparticles in MCF-7 cell line was more than it in HeLa cell line. The average of radiosensitization enhancement factor at 10, 40, and 80 μg/ml concentrations and under 6 MeV irradiations obtained as 1.13, 1.19, 1.25, and 1.26, 1.28, 1.29 for HeLa, and MCF-7 cells, respectively. When 12 MeV electron beams were carried out, the values of 1.17, 1.26, 1.32, and 1.29, 1.32, 1.35 were obtained for the cells at the mentioned concentrations, respectively. Furthermore, the significant differences were observed in radiosensitization enhancement between 6 and 12 MeV electron beams irradiations.

Conclusion: Use of dextran-coated IONPs can increase radiosensitivity and consequently at a given absorbed dose more cell killing will occur in cancerous cells. In other words, these nanoparticles can improve the efficiency of electron therapy.
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http://dx.doi.org/10.4103/jcrt.JCRT_19_17DOI Listing
May 2020

Evaluation of the Cytotoxic and Apoptogenic Effects of Glabridin and Its Effect on Cytotoxicity and Apoptosis Induced by Doxorubicin Toward Cancerous Cells.

Adv Pharm Bull 2019 Aug 1;9(3):481-489. Epub 2019 Aug 1.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran.

In the present study, we tried for the first time to examine the anti-proliferative and anti-apoptogenic effect of Glabridin (Glab) toward three groups of cancer cells (SKNMC, H1299, and A2780). Furthermore, the possibility of co-administration of Glab with doxorubicin (DOX) to these cells was also examined to find out whether Glab can potentiate the cytotoxic effect of this chemotherapy agent. Different cellular assays (MTT, caspase-3 activity, MMP, RT-PCR analysis) were carried out on the cancer cells treated with Glab. Cellular toxicity assay revealed that Glab can potentially reduce the viability of these cells with IC50 concentrations up to 10, 12, and 38 μM toward A2780, SKNMC, and H1299 cell lines, respectively. The results of MMP and caspase-3 activity assays, in association with the results corresponding to the BAX and Bcl-2 gene expressions, altogether revealed that Glab can exert apoptogenic effect on these cells. The intrinsic mitochondrial pathway was found to be the main mechanism, in which Glab induced apoptosis toward H1299 cells and SKNMC cells, while the apoptosis mechanism for A2780 cells could be probably through extrinsic pathway. Glab also potentiated the cytotoxic effect of DOX and its accumulation in H1299 cell line. The results of this study revealed the promising cytotoxic role of Glab on different carcinoma cells. These data also suggested that co-chemotherapy method using Glab could be effective for treatment of cancer, but further in-vivo and clinical studies are still needed to assure these results.
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http://dx.doi.org/10.15171/apb.2019.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773930PMC
August 2019

Ugi efficient synthesis, biological evaluation and molecular docking of coumarin-quinoline hybrids as apoptotic agents through mitochondria-related pathways.

Bioorg Chem 2019 10 27;91:103147. Epub 2019 Jul 27.

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Ric Scalzo Botanical Research Institute, Southwest College of Naturopathic Medicine, Tempe, AZ, USA.

Ugi reaction was a reliable procedure for the synthesis of new coumarin-quinoline frameworks. Excellent yields, mild reaction conditions and easily available and inexpensive starting materials are advantages of this protocol. Cytotoxic effects of fourteen products were investigated in A2780 human ovarian cancer cells. Two synthesized compounds (L11 and L12) exhibited more anti-cancer activity than other derivatives with IC values of 0.042 mmol/L and 0.102 mmol/L, respectively and were thus selected for further studies. Apoptosis was induced through the intrinsic pathway by activating caspase 9 and ended at the executioner pathway of caspase 3. Measurement of intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also carried out for both of them. Further studies on a mechanism by Real Time-PCR and Western blot analysis were performed for anti-apoptotic proteins Bcl-2 and survivin both in mRNA and protein level relating to the untreated A2780 cells. The treatment of A2780 cells with compound L11 significantly (P-value ≤ 0.05) induced apoptosis by down-regulation of Bcl-2 and survivin both in mRNA and protein level via a single dose (0.042 mmol/L), as well as activation of caspase 9 and 3, loss of MMP, and high ROS. Accordingly, findings supported the first report under which the pro-apoptotic activity of compound L11 as an apoptosis-inducing agent was related to mitochondrial-mediated dysfunction signaling pathways. Molecular docking supports experimental outcomes. Evidently, coumarin-quinoline scaffolds are potentially favorable options for further assessment as influential chemotherapeutic agents for the future.
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http://dx.doi.org/10.1016/j.bioorg.2019.103147DOI Listing
October 2019

Cytotoxic and Apoptogenic Sesquiterpenoids from the Petroleum Ether Extract of Aerial Parts.

Iran J Pharm Res 2019 ;18(1):391-399

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Different types of extracts were reported to have various biological activities including a cytotoxic effect on some cancer cell lines. We investigated the antiproliferative activity of isolated sesquiterpenoids from petroleum ether extract of () aerial parts on SK-N-MC, MCF-7, and A2780 cell lines. Phytochemicals from the petroleum ether cold macerated extract were isolated using normal phase vacuum liquid chromatography and high pressure liquid chromatography (VLC and HPLC) and the structures of the components were determined by spectroscopic means. Cell viability was determined by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Activation of caspases-3 and -9 was evaluated using a spectrophotometer. Mitochondrial membrane potential (MMP) was measured using rhodamine 123 fluorescent dye. Two tetrahydrofuran- type sesquiterpenoids, hydroperoxide of davanone (1) and hydroxydavanone (2) were isolated and characterized. Between these compounds, compound 1 exhibited more potent activity against the MCF-7, SK-N-MC and A2780 cell lines with IC values of 8.45 ± 0.81 µg/mL, 9.60 ± 1.32 µg/mL and 10.9 ± 2.03 µg/mL in A2780, MCF-7 and SK-N-MC cells, respectively. Compound 1 inhibited the growth of human cancer cells by induction of apoptosis. To the best of our knowledge, this is the first comprehensive study on cytotoxic and apoptotic mechanism of two davanone derivatives isolated from in human cancer cells. Overall, our data suggest that hydroperoxide of davanone (1) should be further studied as a potential antitumor agent.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487405PMC
January 2019

Investigating the Cytotoxicity of Folate-Conjugated Bismuth Oxide Nanoparticles on KB and A549 Cell Lines.

Adv Pharm Bull 2018 Nov 29;8(4):627-635. Epub 2018 Nov 29.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Lately, bismuth-based nanomaterials have been widely utilized in medical researches such as imaging, drug delivery and radio-sensitization. Despite their advantages, bismuth-based compounds have shown toxic effects in humans. There are few studies on cytotoxicity effects of bismuth oxide (Bi2O3) nanoparticles (NPs) in-vitro. In this study, we aimed to investigate cytotoxicity of bare and also folate and 5-aminolevulinic acid (5-ALA)-conjugated Bi2O3 NPs on nasopharyngeal carcinoma (KB) and lung cancer (A549) cell lines. BO NPs were synthesized and conjugated with folate and 5-ALA. KB and A549 cells were cultured and incubated with 10, 20, 50 and 100 μg/ml concentrations of bare and folate-5-ALA-conjugated NPs. The survival rates were obtained after 2 and 24 hours incubation of the cells with NPs using MTT assay. Also, apoptosis and ROS generation induced by the NPs in the treated cells were obtained using Caspases-3 activity assay and flow cytometry analysis, respectively. BO NPs were successfully synthesized with average size of 19.2 ± 6.5 nm, then conjugated with 5-ALA and folate. Either naked or folate-conjugated NPs were easily taken up by the cells in a concentration-dependent manner and showed cytotoxic effects. The significant cell death was noted at the concentrations more than 50 μg/ml for both compounds. Results indicated low cytotoxicity of the prepared NPs at lower incubation periods, which is very important for their further applications. However, 24 hours incubation of the cells with both forms of NPs caused more cell killing and the cytotoxicity increased with increasing concentrations of the NPs.
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http://dx.doi.org/10.15171/apb.2018.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311633PMC
November 2018

Evaluating the photodynamic therapy efficacy using 5-aminolevulinic acid and folic acid-conjugated bismuth oxide nanoparticles on human nasopharyngeal carcinoma cell line.

Artif Cells Nanomed Biotechnol 2018 15;46(sup3):S514-S523. Epub 2018 Nov 15.

c Nano Drug Delivery Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

Selective accumulation of photosensitizers (PSs) into cancerous cells is one of the most important factors affecting photodynamic therapy (PDT) efficacy. 5-Aminolevulinic acid (5-ALA) is precursor of a strong PS, protoporphyrin-IX (Pp-IX); but it has poor permeability in lipophilic membrane of the cells due to its hydrophilic property. Therefore, establishment of an improved delivery strategy could highly affect on treatment outcome. Moreover, folate receptors (FRs) are overexpressed on the surface of many tumor cells. In the present work, targeting ligand folic acid (FA) and 5-ALA conjugated bismuth oxide nanoparticles (FA-5ALA-BiO NPs) were synthesized; and used in PDT against human nasopharyngeal carcinoma cells (KB cell line). The KB cells incubated with the synthesized NPs for 2 h; then illuminated using a custom-made red light LED lamp at the light dose of 26 J/cm. MTT and caspase-3 activity assays were performed to evaluate the efficacy of treatment. Results showed that FR targeting ligand enables selective endocytosis of FA-5-ALA-conjugated NPs into KB cells. Improved internalization of 5-ALA into cells decreased the cell viability to about 50%, 65%, and 85% in the groups receiving FA-5ALA-BiO NPs, 5ALA-BiO NPs, free 5-ALA and subsequent PDT, respectively. Therefore, FA-5ALA-BiO NPs can significantly increase the cell killing effect of PDT.
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http://dx.doi.org/10.1080/21691401.2018.1501376DOI Listing
June 2019

Diverse Effects of Different "Protein-Based" Vehicles on the Stability and Bioavailability of Curcumin: Spectroscopic Evaluation of the Antioxidant Activity and Cytotoxicity In Vitro.

Protein Pept Lett 2019 ;26(2):132-147

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Curcumin is a natural polyphenolic compound with anti-cancer, antiinflammatory, and anti-oxidation properties. Low water solubility and rapid hydrolytic degradation are two challenges limiting use of curcumin.

Objective: In this study, the roles of the native/modified forms of Bovine Serum Albumin (BSA), β-lactoglobulin (β-lg) and casein, as food-grade biopolymers and also protein chemical modification, in stabilizing and on biological activity of curcumin were surveyed.

Methods: In this article, we used various spectroscopic as well as cell culture-based techniques along with calculation of thermodynamic parameters.

Results: Investigation of curcumin stability indicated that curcumin binding to the native BSA and modified β -lg were stronger than those of the modified BSA and native β -lg, respectively and hence, the native BSA and modified β-lg could suppress water-mediated and light-mediated curcumin degradation, significantly. Moreover, in the presence of the native proteins (BSA and casein), curcumin revealed elevated in vitro anti-cancer activity against MCF-7 (human breast carcinoma cell line) and SKNMC (human neuroblastoma cell line). As well, curcumin, in the presence of the unmodified "BSA and β-lg", was more potent to decrease ROS generation by hydrogen peroxide (H2O2) whereas it led to an inverse outcome in the presence of native casein. Overall, in the presence of the protein-bound curcumin, increased anti-cancer activity and decreased ROS generation by H2O2 in vitro were documented.

Conclusion: It appears that "water exclusion" is major determinant factor for increased stability/ efficacy of the bound curcumin so that some protein-curcumin systems may provide novel tools to increase both food quality and the bioavailability of curcumin as health promoting agent.
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http://dx.doi.org/10.2174/0929866525666181114152242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416488PMC
October 2019

Green and cost-effective synthesis of carbon dots from date kernel and their application as a novel switchable fluorescence probe for sensitive assay of Zoledronic acid drug in human serum and cellular imaging.

Anal Chim Acta 2018 Nov 5;1030:183-193. Epub 2018 May 5.

Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran.

A new label-free, sensitive and selective off and on signaling fluorescence platform for assay of trace levels of Zoledronic acid (ZA) drug in human biological samples based on nitrogen doped carbon dots (N-CDs) - ferric ions (Fe) was designed. The fluorescence probe, N-CDs, was synthesized for the first time through a facile, eco-friendly and one-step hydrothermal treatment using date kernel as the precursor without any need to use chemical reagents. These CDs exhibited excellent water solubility, ionic and photo stability in various circumstances and a highly relative quantum yield of 12.5%. In the presence of Fe, the fluorescence intensity (FL) for N-CDs was strongly quenched due to the interaction between ferric ions and the functional groups at the N-CDs (switch off). Afterwards, by the addition of ZA, the fluorescence sensor status turned to "ON" (switch on) due to the dominance of ZA in the competition between functional groups on the surface of N-CDs and phosphate groups in ZA in the interaction with Fe results in removing Fe from the surface of N-CDs. Under the optimized conditions, the proposed fluorescence probe (N-CDs-Fe) exhibited good sensing performance for ZA assay with a linearity from 0.1 μM to 10.0 μM, a detection limit of 0.04 μM and the precision of 2.70%. The developed N-CDs-Fe sensor was successfully used for the assay of ZA contents with good recoveries and selectivity in human serum samples. Meanwhile, the in vitro cytotoxic activity and cellular uptake of N-CDs were investigated on human osteosarcoma (MG-63) cell line.
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http://dx.doi.org/10.1016/j.aca.2018.05.014DOI Listing
November 2018

Acute and Subchronic Toxicological Evaluations of Allium rotundum L.: A Dietary Plant from Iran.

J Diet Suppl 2019 25;16(3):269-280. Epub 2018 Apr 25.

a Pharmaceutical Sciences Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

Allium rotundum L. is a dietary plant with diverse nutritional and herbal applications. According to its widespread application in Iranians' diets, understanding the possible adverse effects and toxic activities could be of major importance. The aim of this study was to establish the acute and subchronic toxicity profile of the hydroalcoholic extract of Allium rotundum on male and female Wistar rats. The acute study indicated no adverse effect or toxic activity after administration of the extract, suggesting that the LD value is up to 5,000 mg/kg body weight for the extract. The subchronic study at three doses (250, 500, and 750 mg/kg body weight/day) supported the results of acute study and revealed that no abnormal change or toxicity was induced by the extract in both male and female Wistar rats. All the biochemical and hematological parameters of the treated rats were in historical range after long-term administration of the extract. The histopathological examination also revealed no lesion or alteration in the tissue of vital organs (kidney, liver, heart, lung, and spleen). The NOAEL (no observed adverse effect level) value was high enough (greater than 750 mg/kg body weight/ day) to conclude the nontoxic nature of this extract. The safety of this extract was affirmed by the acute and subchronic toxic studies and suggested that this plant could be a proper and effective dietary plant due to its high nutritive value and inherent therapeutic properties.
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http://dx.doi.org/10.1080/19390211.2018.1452325DOI Listing
August 2019

Green Synthesis of Carbon Dots Derived from Walnut Oil and an Investigation of Their Cytotoxic and Apoptogenic Activities toward Cancer Cells.

Adv Pharm Bull 2018 Mar 18;8(1):149-155. Epub 2018 Mar 18.

Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

This paper introduces a green and simple hydrothermal synthesis to prepare carbon quantum dots (CQDs) from walnut oil with a high quantum yield. In addition, cytotoxic and apoptogenic properties of the CQDs were analyzed on human cancer cell lines. The optical properties and morphological characteristic were investigated by the TEM, XRD, FT-IR, UV-vis and photoluminescence (PL).The cytotoxic potential of walnut CQDs was evaluated on PC3, MCF-7 and HT-29 human carcinoma cell lines using the MTT methods. The mechanism of action was studied by investigating the mode of cell death using the activation of caspase-3 and 9 as well as mitochondrial membrane potential (MMP). Cellular uptake of the CQDs was detected by fluorescence microscope. CQDs had an average size of 12 nm and a significant emission at 420 nm at an excitation wavelength of 350 nm was recorded. The prepared CQDs possessed a good fluorescent quantum yield of 14.5% with quinine sulfate (quantum yield 54%) as a reference and excellent photo as well as pH stabilities. The walnut CQDs were proved to be an extremely potent cytotoxic agent, especially against MCF-7 and PC-3 cell lines. Induction of apoptosis by CQDs was accompanied by an increase in the activation of caspase-3. Caspase-9 activity did not increase after exposure to the CQDs. Additionally; the MMP did not show any significant loss. The results of our study can corroborate the cytotoxic and apoptotic effect of walnut CQDs in the PC3 and MCF-7 cancer cell lines.
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http://dx.doi.org/10.15171/apb.2018.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896389PMC
March 2018

The Protective Effect of Different Extracts of Three Species against HO-Induced Oxidative Stress and Apoptosis in PC12 Neuronal Cells.

Pharmacognosy Res 2018 Jan-Mar;10(1):64-71

School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Oxidative stress causes cell damage and is involved in many neurological diseases. The antioxidant properties of plant materials for the maintenance of health and protecting against different diseases stimulated scientist to investigate different herbs. Different species have exhibited antioxidant activity. This study aims to investigate whether different species could protect the PC12 cells against oxidative stress mediated by HO.

Methods: For this purpose, different extracts of three species (, , and ) were prepared using petroleum ether, dichloromethane, ethyl acetate, ethanol, and Water: Ethanol mixture (1:1 volume ratio). The protective effect of the prepared extracts against HO-induced cytotoxicity and reactive oxygen species production were compared. The effect of treatment of PC12 cells with different extracts on total glutathione (GSH) level, caspase-3 activity, and mitochondrial membrane potential were also compared.

Results: The extracts could not rescue the PC12 cells from oxidative stress consequences. The and extracts were found potent in suppressing the toxicity and apoptosis of PC12 cells mediated by HO and significantly antagonized the HO-induced GSH depletion. The hydroethanolic and ethyl acetate extracts of and the petroleum ether and hydroethanolic extracts of more efficiently suppressed cytotoxicity and loss of GSH caused by HO.

Conclusion: This study shows the protective effects of extracts on PC12 cell line and suggested that these species could be also considered as promising neuroprotective agents in treatment of different neurodegenerative diseases.

Summary: and extracts were found to potentially exert neuroprotective effect on PC12 cells. The results exhibited that the cytoprotective potential and anti-apoptotic mechanism of these species is not the same for different extracts, and suggested that based on the type of species and the type of solvents used in extraction, both intrinsic and extrinsic pathways could be included in the anti-apoptotic mechanism of these species. GSH: Glutathion. ROS: Reactive Oxygen Species. GSSG: Glutathione disulfide. DCF-DA:2',7'-Dichlorofluorescin diacetate. FBS: Fetal Bovin Serum. MMP: Mitochondrial Membrane Potential. H-Et: Hydro-ethanolic. DCM: Dichloromethane. PE: Petroleum Ether. Et: Etanolic. EA: Ethyl Acetate.
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http://dx.doi.org/10.4103/pr.pr_98_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855376PMC
March 2018

Direct evidences for the groove binding of the Clomifene to double stranded DNA.

Int J Biol Macromol 2018 Jul 16;114:40-53. Epub 2018 Mar 16.

Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

It has been reported that the antiestrogen Tamoxifen induces liver tumors in rats and genotoxic effects in vitro through DNA interaction. So, it can be proposed that its structural analogue, Clomifene, also can bind to DNA. To test this hypothesis, the DNA binding properties of Clomifene have been studied by absorption spectroscopy, fluorescence spectroscopy, cellular uptake, cell viability, cell proliferation and molecular modeling techniques. Evidences are provided that Clomifene could interact with DNA via minor groove interaction mode. The negative ΔG value implied that the interaction occurred between DNA and Clomifene spontaneously. Also, the positive ΔH and positive ΔS values indicated that the binding of Clomifene with DNA is mainly entropy driven and the enthalpy is unfavorable parameter. This also suggests that the hydrophobic interaction plays a major role in the binding with overall binding constant of K=5.645×10M at 298K. From the results of docking, it can be concluded that Hydrogen bonds is also one of the most important interactions. The increase in entropy of system after binding might be due to the destruction of the DNA structure.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.03.040DOI Listing
July 2018

Potential Anticancer Properties of Osthol: A Comprehensive Mechanistic Review.

Nutrients 2018 Jan 3;10(1). Epub 2018 Jan 3.

Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA.

Cancer is caused by uncontrolled cell proliferation which has the potential to occur in different tissues and spread into surrounding and distant tissues. Despite the current advances in the field of anticancer agents, rapidly developing resistance against different chemotherapeutic drugs and significantly higher off-target effects cause millions of deaths every year. Osthol is a natural coumarin isolated from Apiaceaous plants which has demonstrated several pharmacological effects, such as antineoplastic, anti-inflammatory and antioxidant properties. We have attempted to summarize up-to-date information related to pharmacological effects and molecular mechanisms of osthol as a lead compound in managing malignancies. Electronic databases, including PubMed, Cochrane library, ScienceDirect and Scopus were searched for in vitro, in vivo and clinical studies on anticancer effects of osthol. Osthol exerts remarkable anticancer properties by suppressing cancer cell growth and induction of apoptosis. Osthol's protective and therapeutic effects have been observed in different cancers, including ovarian, cervical, colon and prostate cancers as well as chronic myeloid leukemia, lung adenocarcinoma, glioma, hepatocellular, glioblastoma, renal and invasive mammary carcinoma. A large body of evidence demonstrates that osthol regulates apoptosis, proliferation and invasion in different types of malignant cells which are mediated by multiple signal transduction cascades. In this review, we set spotlights on various pathways which are targeted by osthol in different cancers to inhibit cancer development and progression.
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http://dx.doi.org/10.3390/nu10010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793264PMC
January 2018

Bioassay-guided Isolation of Neuroprotective Fatty Acids from against 1-methyl-4-phenylpyridinium-induced Neurotoxicity.

Pharmacogn Mag 2017 Oct-Dec;13(52):627-633. Epub 2017 Nov 13.

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objective: Parkinson's disease, a slowly progressive neurological disease, is associated with degeneration of the basal ganglia of the brain and a deficiency of the neurotransmitter dopamine. The main aspects of researches are the protection of normal neurons against degeneration. Fatty acids (FAs), the key structural elements of dietary lipids, are carboxylic straight chains and notable parameters in nutritional and industrial usefulness of a plant.

Materials And Methods: Black cumin, a popular anti-inflammatory and antioxidant food seasoning, contains nonpolar constituents such as FAs which were extracted using hexane. Different fractions and subfractions were apt to cytoprotection against apoptosis and inflammation induced by 1-methyl-4-phenylpyridinium (MPP) in rat pheochromocytoma cell line (PC12) as a neural cell death model. The experiment consisted of examination of cell viability assessment, mitochondrial membrane potential (MMP), caspase-3 and -9 activity, and measurement of cyclooxygenase (COX) activity.

Results: MPP induced neurotoxicity in PC12 cells. Pretreatment with subfractions containing FA mixtures attenuated MPP-mediated apoptosis partially dependent on the inhibition of caspase-3 and -9 activity and increasing the MMP. A mixture of linoleic acid, oleic acid, and palmitic acid also decreased the COX activity induced by MPP in PC12 cells.

Conclusion: Our observation indicated that subtoxic concentration of FA from may exert cytoprotective effects through their anti-apoptotic and anti-inflammation actions and could be regarded as a dietary supplement.

Summary: MPP induced neurotoxicity in PC12 cells contains bioactive fatty acidsPretreatment with fatty acids attenuated MPP+ mediated apoptosis through inhibition of caspase 3 and 9 activityA mixture of linoleic acid, oleic acid, and palmitic acid decreased the COX activity induced by MPP in PC12 cellsDue to cytoprotective, anti apoptotic and anti inflammation actions of , it could be regarded as a dietary supplement. ANOVA: Analysis of variance; Ca: Calcium; CDCl3: Chloroform; COX: Cyclooxygenase; DMSO: Dimethyl sulfoxide; EA: Elidic acid; EDTA: Ethylene diamine tetraacetic acid; ELISA: Enzyme Linked Immunosorbent Assay; ESI-MS: Electron spray mass spectroscopy; FAs: Fatty acids; FBS: Fetal bovine serum; GC: Gas chromatography; 1HNMR: Hydrogen nuclear magnetic resonance; LA: Linoleic acid; MPP+: 1-Methyl-4-phenylpyridinium; MPTP: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine; MTT: 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide; : ; OA: Oleic acid; PA: Palmitic acid; PBS: Phosphate buffer saline; PC12: Rat pheochromocytoma cell line; PD: Parkinson's disease; PDA: Photo diode array detector; PGE2: Prostaglandin E2; TLC: Thin layer chromatography; TMPD: N,N,N',N'-tetramethyl-p-phenylenediamine; USA: United states of America.
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http://dx.doi.org/10.4103/pm.pm_470_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701402PMC
November 2017

Synthesis and cytotoxic evaluation of some new 3-(2-(2-phenylthiazol-4-yl) ethyl)-quinazolin-4(3H) one derivatives with potential anticancer effects.

Res Pharm Sci 2017 Aug;12(4):290-298

Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Science, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

Quinazolinones are a group of heterocyclic compounds that have important biological activities such as cytotoxicity, anti-bacterial, and anti-fungal effects. Thiazole-containing compounds have also many biological effects including antitumor, antibacterial, anti-inflammatory, and analgesic activities. Due to significant cytotoxic effects of both quinazoline and thiazole derivatives, in this work a group of quinazolinone-thiazol hybrids were prepared and their cytotoxic effects on three cell lines were evaluated using MTT assay. Compounds , , , and showed highest cytotoxic activities against PC3 cell line. Compounds , , and were most active against MCF-7 and , , and showed good cytotoxic effect on HT-29 cell line. According to the results, efficiently inhibited all cell growth tested in a dose dependent manner. The IC50 of A3 was 10 M, 10 μM, and 12 μM on PC3, MCF-7, and HT-29 cells, respectively.
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http://dx.doi.org/10.4103/1735-5362.212046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566003PMC
August 2017

Protective effect of bioactive compounds from against cisplatin-induced oxidative stress and apoptosis in the PC12 cell line.

Iran J Basic Med Sci 2017 Apr;20(4):438-445

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objectives: The present study aims to evaluate the protective effect of the compounds isolated from () against oxidative stress and apoptosis induced by cisplatin (CIS) in PC12 cells.

Materials And Methods: Six compounds were isolated as quercetrin-3---D-glucopyranoside (QUE), osthol (OST), verbenone-5---D-glycopyranoside (VER), Isoimperatorin (ISO), kaempferol-3---D-glucopyranoside (KAM), and echinophorin B (ECH). For this study, we used MTT reduction assay for detection of protective effects of isolated compounds on CIS-induced cytotoxicity in PC12 cells. The effects of isolated compounds against apoptosis induced by CIS were investigated through the measurement of mitochondrial membrane potential (MMP), Bax and Bcl2 mRNA expression, and caspase-3 activation. We also assessed oxidative stress by measuring reactive oxygen species (ROS) generation with 2', 7'-dichlorofluorescein diacetate (DCFH-DA).

Results: Treatment of cells with QUE and OST before exposure to the CIS increased cell viability, i.e., these compounds protected the cells against CIS -induced cytotoxicity. In addition, pre-treatment with QUE and OST decreased CIS-induced apoptosis through up-regulation of Bcl-2, inhibition of caspase-3 activity, and mitochondrial membrane potential (MMP) increase. OST decreased ROS generation induced by CIS, as well.

Conclusion: Our experiment showed that QUE and OST are apoptotic inhibitors that effectively block CIS-induced neurotoxicity predicting their therapeutic potential in the prevention of chemotherapy-induced neurotoxicity.
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http://dx.doi.org/10.22038/IJBMS.2017.8587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425927PMC
April 2017

Radiation dose rate affects the radiosensitization of MCF-7 and HeLa cell lines to X-rays induced by dextran-coated iron oxide nanoparticles.

Int J Radiat Biol 2017 08 17;93(8):757-763. Epub 2017 May 17.

a Department of Medical Physics, Faculty of Medicine , Kermanshah University of Medical Sciences , Kermanshah , Iran.

Background And Purpose: The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced radiosensitivity by dextran-coated iron oxide in cancer cells.

Materials And Methods: HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations.

Results: Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 μg/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more radiosensitivity effect by increasing the dose rate and nanoparticles concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 μg/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively.

Conclusion: Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the radiosensitization induced by the dextran-coated iron nanoparticles in these cells.
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http://dx.doi.org/10.1080/09553002.2017.1321806DOI Listing
August 2017

New polyacetylenes from Echinophora cinerea (Boiss.) Hedge et Lamond.

Nat Prod Res 2017 Oct 10;31(19):2256-2263. Epub 2017 Mar 10.

d Biotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.

Echinophora cinerea aerial parts are used in folk medicine to cure gastric diseases and as a food seasoning in cheese and yogurt. Besides several pharmacological effects have been assigned to Echinophora spp., there is no phytochemical investigation on this genus other than our previous publication on flavonoids. An acetone extract of E. cinerea afforded three new (1-3) polyacetylenes, one rare monoterpenoid glycoside as verbenone-5-O-β-D-glycopyranoside (4) and one prenylated coumarin as osthol (5). The structures of all new compounds were elucidated using modern spectroscopic methods, including 2D NMR and mass analyses. The potency of the compounds to induce cell death was determined on SKNMC, PC3 and MCF-7 cell lines using MTT method in which compounds 1 and 2 showed moderate cytotoxic effects, especially against PC3 cells.
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http://dx.doi.org/10.1080/14786419.2017.1300797DOI Listing
October 2017

The Role of Nanoparticle in Brain Permeability: An in-vitro BBB Model.

Iran J Pharm Res 2016 ;15(2):403-13

Department of Pharmaceutics, Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.

Membrane permeability and P-glycoprotein (P-gp) efflux system are regulating factors in the drug brain penetration. Recently, some drug delivery systems have been developed to overcome these limitations. In this study, Metoclopramid has been encapsulated in PLGA nanoparticles using the emulsification/solvent evaporation technique for in-viro evaluation of the effect of PLGA nanoparticles on BBB permeability. Subsequently, prepared nanoparticles were characterized using PCS, TEM, FT-IR, DSC and XRD techniques and in-viro cell permeability of optimum formulation was evaluated using MDCK cell line as BBB model. Data investigation showed that prepared nanoparticles have the entrapment efficiency of 50 %. PCS investigation showed that prepared nanoparticles have an average size of approximately 150 ± 14 nm and a relatively monodisperse distribution. TEM micrographs of the samples showed spherical shape and smooth surface with a particle size of nanometric range. Through DSC thermograms and XRD diffractograms analysis, it was demonstrated that there was no crystalline form of the drug in the loaded formulation. Moreover, our results showed that the greater crossing of metoclopramide in the form of nanoparticle in comparison with the free form. The widely used rhodamine-123 transport assay performed in the MDCK cells demonstrated the presence of P-glycoprotein in this model.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018268PMC
September 2016

Synthesis and cytotoxicity evaluation of some new 6-nitro derivatives of thiazole-containing 4-(3H)-quinazolinone.

Res Pharm Sci 2016 May-Jun;11(3):210-8

Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Science, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

Quinazolinones are a group of fused heterocyclic compounds which have valuable biological properties including cytotoxic, antibacterial and antifungal activities. Thiazole group-containing compounds have been also reported to have a wide range of biological activities such as antitumor, anti-inflammatory, analgesic and antibacterial effects. Due to valuable cytotoxic effects of both thiazole groups and quinazoline derivatives, in this study a series of quinazolinone-thiazole hybrids were synthesized and evaluated for their cytotoxic effects on three cell lines including MCF-7, HT-29, and PC-3. Among tested compounds (quinazolinones and three intermediates), k5 and k6 showed highest cytotoxic activities against PC3 cell line. K6 and C were most active compounds against MCF7 and K6 showed best cytotoxicity on HT-29 cell line.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962301PMC
August 2016

Protective effects of fractions from Artemisia biennis hydro-ethanolic extract against doxorubicin-induced oxidative stress and apoptosis in PC12 cells.

Iran J Basic Med Sci 2016 May;19(5):503-10

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objectives: This study was designed to indicate whether different fractions from Artemisia biennis hydroethanolic extract could provide cytoprotection against oxidative stress and apoptosis induced by doxorubicin (DOX) in rat pheochromocytoma cell line (PC12).

Material And Methods: Cell viability was determined by MTT assay. Also, activation of caspase-3 and superoxide dismutase were evaluated by spectrophotometry. Detection of reactive oxygen species (ROS) and measurement of mitochondrial membrane potential (MMP) were performed by flowcytometry.

Results: Treatment of PC12 cells with DOX reduced viability dose dependently. For evaluation of the effect of fractions (A-G) on DOX-induced cytotoxicity, PC12 cells were pretreated for 24 hr with the A. biennis fractions and then cells were treated with DOX. The fractions C and D increased PC12 cells viability significantly compared to DOX treated cells. Moreover, pretreatment with fractions C and D for 24 hr attenuated DOX-mediated apoptosis and the anti-apoptotic action of A. biennis fractions was partially dependent on inhibition of caspase 3 activity and also increasing the mitochondrial membrane potential (MMP). Selected A. biennis fractions also suppressed the generation of ROS and increased superoxide dismutase (SOD) activity.

Conclusion: Taken together our observation indicated that subtoxic concentration of aforementioned fractions of A. biennis hydroetanolic extract has protective effect against apoptosis induced by DOX in PC12 cell. The results highlighted that fractions C and D may exert cytoprotective effects through their antioxidant actions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923471PMC
May 2016

Zinc Finger 259 Gene Polymorphism rs964184 is Associated with Serum Triglyceride Levels and Metabolic Syndrome.

Int J Mol Cell Med 2016 ;5(1):8-18

Department of Modern Science and Technologies; and Biochemistry of Nutrition Research Center; School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors that include: abdominal obesity, dyslipidaemia, hypertension, insulin resistance and impaired glucose tolerance. Recent genome wide association studies have identified several susceptibility regions involved in lipid metabolism that are also associated with MetS. We have explored the association of 9 genetic polymorphisms involved in lipid metabolism and hypertension, including: MTHFR C677T, SELE L554F, FGB - 455G>A, GNB3 C825T, ZNF259 C>G, PSRC-1 A>G, CETP I405V, LPL S447X and LPA C>T in 97 subjects with MetS and 96 individuals without MetS who were recruited randomly from Mashhad stroke and heart atherosclerotic disorder (MASHAD) study using a stratified cluster random sampling technique. Anthropometric parameters and biochemical measurements were determined in all the subjects. Genotyping was carried out followed by univariate and multivariate analyses. The subjects with MetS had a higher triglyceride and lower HDL- C. CG+ GG genotypes of ZNF259 polymorphism (rs964184 C>G) and TT+CT genotypes of MTHFR C677T (rs1801133) were associated with MetS, and individuals carrying the G allele for ZNF259 or the T allele for MTHFR polymorphisms were associated with MetS (e.g, odds ratio (OR) for CG+GG genotypes vs. CC wild type: 2.52, CI=1.33-4.77; P=0.005). However, after multiple comparison adjustment, this relationship remained significant only for CG+ GG genotypes of ZNF259 polymorphism. Moreover, the ZNF259 CG+ GG genotypes were associated with increased serum concentrations of triglycerides and LDL-C, compared to the wild type. These data support the necessity for further studies in larger multicenter settings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916779PMC
July 2016

Evaluation of antioxidant and cytoprotective activities of Artemisia ciniformis extracts on PC12 cells.

Iran J Basic Med Sci 2016 Apr;19(4):430-8

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objectives: In the current study antioxidant capacities of five different extracts of Artemisia ciniformis aerial parts were evaluated by cell-free methods. Then seven fractions of the potent extract were selected and their antioxidant capacity was assayed by cell free and cell based methods.

Materials And Methods: Antioxidant ability was measured using the: 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test, β-carotene bleaching (BCB) method and ferrous ion chelating (FIC) assay. Total phenolic contents (TPC) of all the samples also were determined. The cytoprotective effect of fractions was evaluated by measuring the viability of cells after exposure to doxorubicin (DOX). The mechanism of action was studied by investigating caspase-3, mitochondrial membrane potential (MMP), the level of super-oxide dismutase (SOD) and intracellular reactive oxygen species (ROS).

Results: Hydroethanolic extract exhibited a notably higher antioxidant activity and phenolic content. Among the fractions (A to G) of hydroethanolic extract, the highest antioxidant capacity was observed in the Fraction E. Moreover, 24 hr pretreatment of PC12 cells with fractions B, C and D decreased DOX-induced cytotoxicity. In addition, pre-treatment of cells with fraction B resulted in significant decrease in generation of the reactive oxygen species (ROS) and increase in the activity of SOD. We were able to demonstrate remarkable reduction in the activity of caspase-3 and increase in MMP in PC12 cells following pretreatment with fraction B.

Conclusion: Our observations indicated that the fraction B of A. ciniformis hydroetanolic extract possessed protective effect on oxidative stress and apoptosis induced by DOX in PC12 cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887717PMC
April 2016
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