Publications by authors named "Alireza Samzadeh-Kermani"

18 Publications

  • Page 1 of 1

Protective Effect of Haw Fruit against Lead Acetate-Induced Hepatotoxicity: and Studies.

Evid Based Complement Alternat Med 2021 29;2021:6698345. Epub 2021 Apr 29.

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Lead is one of the most common environmental contaminants in the Earth's crust, which induces a wide range of humans biochemical changes. Previous studies showed that () fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor- (TNF-) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( < 0.001 for all cases). (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( < 0.001-0.05 for all cases). (20, 40, and 80 g/ml) concentration dependently and significantly reduced the levels of MDA and TNF-, while it increased the levels of GSH and cell viability in comparison to the Pb group ( < 0.001-0.05 for all cases). These data suggest that may have hepatoprotective effects against Pb-induced liver toxicity both and by its antioxidant and anti-inflammatory activities.
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http://dx.doi.org/10.1155/2021/6698345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105112PMC
April 2021

Administration of Selenium Nanoparticles Reverses Streptozotocin-Induced Neurotoxicity in the male rats.

Metab Brain Dis 2021 Aug 7;36(6):1259-1266. Epub 2021 Apr 7.

Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Alzheimer's disease is the most common neurodegenerative disease associated with deposition of amyloid-beta and the increased oxidative stress. High free radical scavenging ability of selenium nanoparticles (SeNPs) has been acknowledged, so in the present study, the effects of treatment with SeNPs on Streptozotocin (STZ)-induced neurotoxicity were evaluated in the male rats. Learning and memory impairment was induced by intraventricular injection of STZ. Following induction of memory impairment, the rats received 0.4 mg/kg of SeNPs daily for one month. Memory function, antioxidant capacity, and deposition of Amyloid β (Aβ) were assessed using the shuttle box task, biochemical methods, and Congo red staining. Injection of STZ caused memory impairment, a decrease in the level of total thiol group (TTG), and an increase in the malondialdehyde (MDA) content and deposition of Aβ. Administration of SeNPs reversed the neurotoxicity induced by STZ. It seems that SeNPs likely had neuroprotective effects on the animal model of Alzheimer's disease through increasing antioxidants҆ capacity.
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http://dx.doi.org/10.1007/s11011-021-00713-8DOI Listing
August 2021

Synergistic effects of adipose-derived mesenchymal stem cells and selenium nanoparticles on streptozotocin-induced memory impairment in the rat.

Life Sci 2021 May 16;272:119246. Epub 2021 Feb 16.

Endometrium and Endometriosis Research Centre, Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Aims: Memory impairment is determined to be the most well-known symptom of Alzheimer's disease (AD). Although cell therapy seems is an efficient therapeutic strategy to attenuate the AD-related memory impairment, transplanted cells have a short lifespan and do not survive long term in the recipient animals. Herein, we investigated whether the combination therapy of Selenium nanoparticles (SeNPs) and stem cells attenuates the neurotoxicity in an AD animal model.

Material And Methods: The adipose-derived mesenchymal stem cells (AMSCs) were transplanted in the AD model. In addition to cell injections, the animals also received oral administration of SeNPs (0.4 mg/kg) for one month. Recognition memory, cell survival, and BDNF concentration were assessed using the novel object recognition task, immunofluorescence, and ELISA methods.

Key Findings: Our results showed that the combined therapy was more effective in increasing the discrimination index than the administering SeNPs or AMSCs alone. Moreover, SeNPs and stem cells together had the greatest effects in reducing the deposition of Aβ and increasing the concentration of BDNF. Ultimately, the survival and proliferation of transplanted cells were more in the group that received stem cells besides SeNPs.

Significance: Taken together, it seems that the transplantation of MSCs combined with SeNPs could achieve better results in the neuroprotection in the AD model than a conventional treatment of SeNPs or stem cells alone.
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http://dx.doi.org/10.1016/j.lfs.2021.119246DOI Listing
May 2021

Magnetic carnosine-based metal-organic framework nanoparticles: fabrication, characterization and application as arsenic adsorbent.

J Environ Health Sci Eng 2020 Dec 16;18(2):1163-1174. Epub 2020 Sep 16.

Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

This study centers on the controllable synthesis, characterization, and application of a novel magnetic bio-metal-organic framework (Bio-MOF) for the adsorption and subsequent removal of arsenic from aqueous solutions. Zinc ions and carnosine (Car) were exploited to construct the Car-based MOF on the surface of magnetite (FeO NPs). The Magnetite precoating with Car led to an increase in the yield and the uniform formation of the magnetic MOF. The prepared magnetic Bio-MOF nanoparticles (FeO-Car-MOF NPs) had semi-spherical shape with the size in the range of 35-77 nm, and the crystalline pattern of both magnetite and Car-based MOF. The NPs were employed as an adsorbent for arsenic (As) removal. The adsorption analyses revealed that all studied independent variables including pH, adsorbent dose, and initial arsenic concentration had a significant effect on the arsenic adsorption, and the adsorption data were well matched to the quadratic model. The predicted adsorption values were close to the experimental values confirming the validity of the suggested model. Furthermore, adsorbent dose and pH had a positive effect on arsenic removal, whereas arsenic concentration had a negative effect. The adsorption isotherm and kinetic studies both revealed that As adsorption fitted best to the Freundlich isotherm model. The maximum monolayer adsorption capacity (94.33 mg/g) was achieved at room temperature, pH of 8.5 and adsorbent dose of 0.4 g/L. Finally, the results demonstrated that the adsorbent could be efficiently applied for arsenic removal from aqueous environment.
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http://dx.doi.org/10.1007/s40201-020-00535-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721956PMC
December 2020

Evaluation of the Effects of Peritoneal Lavage with Rosmarinus officinalis Extract against the Prevention of Postsurgical-Induced Peritoneal Adhesion.

Planta Med 2020 Apr 25;86(6):405-414. Epub 2020 Feb 25.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Postoperative adhesions are regarded as the major complication following abdominal surgery. has shown antioxidative and anti-inflammatory effects. Therefore, we aimed to assess the influence of 70% v/v hydro-ethanolic extract of the aerial parts of against postoperative abdominal adhesions in a rat model. Forty-eight male Wistar rats (190 ± 20 g) were divided into six groups of eight: group 1 = normal group, without any surgical procedures, group 2 = control group, group 3 = vehicle group, and groups 3, 4, and 5 = experimental groups receiving 2 mL of 4, 2, or 1% w/v treatment. Adhesion levels were macroscopically examined. Additionally, the levels of inflammatory cytokines (interleukin-6, interleukin-1, and TNF-), growth factors (transforming growth factor-1, and vascular endothelial growth factor), oxidative (NO, nitric oxide and MDA, malondialdehyde), and antioxidative (GSH, glutathione) factors were evaluated. Our results revealed that the adhesion score, interleukin-6, interleukin-1, TNF-, transforming growth factor-1, vascular endothelial growth factor, NO, and MDA levels were significantly increased in the vehicle group, while the GSH level was diminished. treatment notably ameliorated the adhesion score following postoperative abdominal adhesions compared with the vehicle group. Our results also revealed that markedly reduced inflammatory cytokines, oxidative factors, fibrosis, and angiogenesis biomarkers, whereas it increased the antioxidative factor. Therefore, may be a potential candidate for the management of postoperative peritoneal adhesion.
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http://dx.doi.org/10.1055/a-1118-3918DOI Listing
April 2020

Crocin protects cardiomyocytes against LPS-Induced inflammation.

Pharmacol Rep 2019 Dec 30;71(6):1228-1234. Epub 2019 Jul 30.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Sepsis causes organ dysfunctions via elevation of oxidative stress and inflammation. Lipopolysaccharide (LPS) is the major surface molecule of most gram-negative bacteria and routinely used as a sepsis model in investigation studies. Crocin is an active compound of saffron which has different pharmacological properties such as anti-oxidant and anti-inflammatory. In this research, the protective effect of crocin was evaluated against LPS-induced toxicity in the embryonic cardiomyocyte cell line (H9c2).

Methods: The cells were pre-treated with different concentration of crocin (10, 20 and 40 μM) for 24 h, and then LPS was added (10 μg/ml) for another 24 h. Afterward, the percentage of cell viability and the levels of inflammatory cytokines (TNF-α, PGE, IL-1β, and IL-6), gene expression levels (TNF-α, COX-2, IL-1β, IL-6, and iNOS), and the level of nitric oxide (NO) and thiol were measured.

Results: Our results showed that LPS reduced cell viability, increased the levels of cytokines, gene-expression, nitric oxide, and thiol. Crocin attenuated the LPS-induced toxicity in H9c2 cells via reducing the levels of inflammatory factors (TNF-α, PGE, IL-1β, and IL-6, p < 0.001), gene expression (TNF-α, COX-2, IL-1β, IL-6, and iNOS, p < 0.001), and NO (p < 0.001), whereas increased the level of thiol content (p < 0.001).

Conclusion: The observed results revealed that crocin has preventive effects on the LPS induced sepsis and its cardiac toxicity in-vitro model. Probably, these findings are related to anti-inflammatory and anti-oxidant properties of crocin. However, performing further animal studies are necessary to support the therapeutic effects of crocin in septic shock cardiac dysfunction.
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http://dx.doi.org/10.1016/j.pharep.2019.07.007DOI Listing
December 2019

Evaluation of Antioxidant and Antibacterial Potential of GreenSynthesized Silver Nanoparticles Using Fruit Extract.

Iran J Pharm Res 2019 ;18(1):430-455

Department of Biology, Faculty of Science Urmia University, Urmia, Iran.

Nowadays, green synthesis of metal nanoparticles has become a promising synthetic strategy in nanotechnology and materials sciences. In this research, biosynthesis of silver nanoparticles (AgNPs) was successfully accomplished in the presence of fruit extract as a reducing agent. Proceeding of the reaction was assessed by using UV-vis spectroscopy. Characterization of silver nanoparticles was carried out by X-ray Diffraction spectroscopy (XRD) and transmission electron microscopy (TEM). The influence of process variables such as temperature, reaction time, and extract concentration was also investigated to optimize the biosynthesis of silver nanoparticles. The average size of synthesized AgNPs was 12.68 nm (10.26-14.65 nm). Furthermore, fruit extract and AgNPs were evaluated for total phenolic and flavonoid contents and were subjected to determine their antiradical scavenging activity using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay and antimicrobial activity against , , , using the disk diffusion method. The total phenols and flavonoids in AgNPs-containing plant extract were 462.69 (mg GAE/g extract) and 386.94 (mg QE/g extract) respectively, which were significantly higher than fruit extract. Biosynthesized AgNPs showed a higher antioxidant and antibacterial activity compared to fruit extract alone. It could be concluded that fruit extract can be extensively used in the production of potential antioxidant and antibacterial AgNPs for biomedical application.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487442PMC
January 2019

Anti-Inflammatory and Anti-Oxidant Activity of Extract on LPS-Induced Rat Lung Injury.

Molecules 2019 Jan 1;24(1). Epub 2019 Jan 1.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are classified as two lung complications arising from various conditions such as sepsis, trauma, and lung inflammation. Previous studies have shown that the extract of the leaves of (PO) possesses anti-inflammatory and anti-oxidant activities. In the present study, the effects of PO (50⁻200 mg/kg) and dexamethasone (Dexa; 1.5 mg/kg) on lipopolysaccharide (LPS)-induced ALI were investigated. Subsequentially, the lung wet/dry ratio; white blood cells (WBC); levels of nitric oxide (NO); myeloperoxidase (MPO); malondialdehyde (MDA); thiol groups formation; super oxide dismutase (SOD) and catalase (CAT) activities; and levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-10, prostaglandin E2 (PGE₂), and transforming growth factor (TGF)-β in the broncho alveolar lavage fluid (BALF) were evaluated in order to demonstrate the anti-oxidant and anti-inflammatory activity of PO. Our results show that PO suppresses lung inflammation by the reduction of IL-β, IL-6, TNF-α, PGE₂, and TGF-β, as well as by the increase of IL-10 levels. We also found that PO improves the level of WBC, MPO, and MDA, as well as thiol group formation and SOD and CAT activities, compared with the LPS group. The results of our investigation also show that PO significantly decreased the lung wet/dry ratio as an index of interstitial edema. Taken together, our findings reveal that PO extract dose-dependently displays anti-oxidant and anti-inflammatory activity against LPS-induced rat ALI, paving the way for rational use of PO as a protective agent against lung-related inflammatory disease.
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http://dx.doi.org/10.3390/molecules24010139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337267PMC
January 2019

Synthesis and biological evaluation of new N-benzylpyridinium-based benzoheterocycles as potential anti-Alzheimer's agents.

Bioorg Chem 2019 03 13;83:559-568. Epub 2018 Nov 13.

The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran; Departmnt of Pharmaceutical Biomaterials, Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with pyridin-4-carbalehyde, followed by N-benzylation using various benzyl halides. The results of in vitro biological assays revealed that most of them, especially 4c and 4g, had potent anticholinesterase activity comparable or more potent than reference drug, donepezil. The kinetic study demonstrated that the representative compound 4c inhibits AChE in competitive manner. According to the ligand-enzyme docking simulation, compound 4c occupied the active site at the vicinity of catalytic triad. The compounds 4c and 4g were found to be inhibitors of Aβ self-aggregation as well as AChE-induced Aβ aggregation. Meanwhile, these compounds could significantly protect PC12 cells against HO-induced injury and showed no toxicity against HepG2 cells. As multi-targeted structures, compounds 4c and 4g could be considered as promising candidate for further lead developments to treat Alzheimer's disease.
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http://dx.doi.org/10.1016/j.bioorg.2018.11.010DOI Listing
March 2019

Novel 3-phenylcoumarin-lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease.

Bioorg Chem 2018 09 2;79:223-234. Epub 2018 May 2.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

New series of triazole-containing 3-phenylcoumarin-lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against HO-induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations. Based on the obtained results, the benzocoumarin derivative 4j with IC value of 7.3 µM was the most potent AChE inhibitor and displayed good inhibition toward intracellular reactive oxygen species (ROS). This compound with antioxidant and metal chelating ability showed also protective effect on cell injury induced by Aβ in SH-SY5Y cells. Although the 8-methoxycoumarin analog 4i was slightly less active than 4j against AChE, but displayed higher protection ability against HO-induced cell death in PC12 and could significantly block Aβ-aggregation. The results suggested that the prototype compounds 4i and 4j might be promising multi-functional agents for the further development of the disease-modifying treatments of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.bioorg.2018.04.030DOI Listing
September 2018

β-Amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-γ and regulates Mφ/Mφ balances.

Biomed Pharmacother 2018 May 22;101:438-446. Epub 2018 Mar 22.

Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran. Electronic address:

Background: Inflammation is a primary response to infection that can pathologically lead to various diseases including neurodegenerative diseases. The purpose of this study was to evaluate the effect of β-Amyrin, a naturally occurring pentacyclic triterpenoid compound, on inflammation induced by lipopolysaccharide (LPS) and interferone-γ (IFN-γ) in rat microglial cells.

Materials And Methods: Cytotoxicity of β-Amyrin (3-100) μM on microglial cells was evaluated using the MTT assay. Also, the protective effect of various β-Amyrin (2-16 μM) concentrations with LPS/IFN-γ-induced mice microglial cells was studied. The concentrations of TNF-α (Tumor Necrosis Factor-α), IL-1β (Interleukin-1β), IL-6 (Interleukin-6) and PGE-2 (Prostaglandin E2) were evaluated using ELISA. Gene expressions of TNF-α, IL-1β, IL-6, COX-2 (Cyclooxygenase-2), iNOS and arginase-1 were also evaluated using the Real-Time PCR method. Nitrite oxide and urea were measured using biochemical methods.

Results: The studied concentrations ​​of β-Amyrin had no significant effects on the viability of microglial cells. Interestingly, β-Amyrin concentration dependently and significantly increased the reduced cell proliferation concerning to LPS/IFN-γ exposure (p < 0.001). The concentrations and expression levels of pro-inflammatory factors including TNF-α, IL-1β, IL-6, PGE-2, COX-2 were significantly reduced after β-Amyrin treatment in LPS/IFN-γ-induced microglial cells (p < 0.05-0.001). β-Amyrin also decreased the levels of nitric oxide, increased urea and down regulated the expression of nitric oxide synthesis while arginase-1 expression was enhanced (p < 0.001). The ratio of NO/urea and iNOS/Arg1 were also markedly increased in comparison to the LPS/IFN-g group (p < 0.001).

Conclusion: β-Amyrin reduces inflammation in microglial cells and can be used as a potential anti-inflammatory agent in central nervous system neurodegenerative diseases such as Alzheimer and multiple sclerosis, by affecting the inflammatory cytokine and differentiation of microglia as resident CNS macrophages.
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http://dx.doi.org/10.1016/j.biopha.2018.02.098DOI Listing
May 2018

Green One-pot Synthesis of Novel Polysubstituted Pyrazole Derivatives as Potential Antimicrobial Agents.

Acta Chim Slov 2017 Dec;64(4):911-918

Various biological properties of natural and synthetic pyrazole derivatives such as anti-inflammatory, antimicrobial, neuroprotective, anticonvulsant, antidepressant and anticancer activities encouraged us to propose a new, fast, green and eco-friendly procedure for the preparation of some novel 5-amino-3-(aryl substituted)-1-(2,4-dinitrophenyl)-1H-pyrazole-4-carbonitriles. They were efficiently synthesized via one-pot two-step process reaction of malononitrile, 2,4-dinitrophenylhydrazine and different benzaldehydes in deep eutectic solvent (DES) glycerol/potassium carbonate. The products yield and reaction times were considerably improved in the presence of applied DES. Antibacterial effects of all newly synthesized pyrazoles in comparison with several common antibiotics were evaluated against a variety of Gram-positive and Gram-negative pathogenic bacteria. In addition to, their inhibitory activities on three fungi were compared to some current antifungal agents. The moderate to good antimicrobial potentials particularly against fungi were observed in the major heterocyclic compounds according to the IZD, MIC, MBC and MFC results.
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http://dx.doi.org/10.17344/acsi.2017.3609DOI Listing
December 2017

MgO Nanoparticle-Catalyzed Synthesis and Broad-Spectrum Antibacterial Activity of Imidazolidine- and Tetrahydropyrimidine-2-Thione Derivatives.

Appl Biochem Biotechnol 2018 Jan 5;184(1):291-302. Epub 2017 Jul 5.

Young Researchers and Elite Club, Kerman Branch, Islamic Azad University, Kerman, Iran.

The biological properties of imidazolidine- and tetrahydropyrimidine-2-thione derivatives such as antiviral, antitumor, anti-inflammatory, and analgesic activities increase the demand for mild and efficient synthetic routes. In this regard, methods such as reaction of diaminoalkanes with carbon disulfide have been developed. However, this method usually suffers from relatively long reaction times, using excess reagents, vigorous reaction conditions, and emission of pernicious hydrogen sulfide gas. In this project, MgO nanoparticle was used as an efficient, non-toxic, recyclable, and economic catalyst to synthesize cyclic five- or six-membered thioureas 3a-h via reaction of 1:1 molar ratios of 1,2- or 1,3-diaminoalkanes 1a-h and carbon disulfide in ethanol at ambient temperature. More interestingly, no hydrogen sulfide emission was detected during the reaction progress. The in vitro antimicrobial properties of synthesized compounds were investigated against 14 different Gram-positive and Gram-negative pathogenic bacteria according to CLSI (Clinical and Laboratory Standards Institute) broth microdilution and disk diffusion methods. The results were compared to those of penicillin, gentamicin, and ceftriaxone, and reported as inhibition zone diameter (IZD), the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC) values. The best inhibitory effects were observed with imidazolidine-2-thiones 3c and 3d. They were effective against 14 and 11 pathogens, respectively. The structure-activity relationships of the prepared heterocyclic compounds were also studied.
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http://dx.doi.org/10.1007/s12010-017-2544-yDOI Listing
January 2018

Effects of adenosine A2a receptor agonist and antagonist on cerebellar nuclear factor-kB expression preceded by MDMA toxicity.

Med J Islam Repub Iran 2014 26;28:120. Epub 2014 Oct 26.

6. PhD, Professor of Anatomical Sciences, Cellular and Molecular Research Center, Faculty of Advanced Technology in Medicine, Department of Anatomy, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Background: Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliated emotional response. MDMA is a potent monoaminergic neurotoxin with the potential of damage to brain neurons. The NF-kB family of proteins are ubiquitously expressed and are inducible transcription factors that regulate the expression of genes involved in disparate processes such as immunity and ingrowth, development and cell-death regulation. In this study we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration.

Methods: Sixty three male Sprague-Dawley rats were injected to MDMA (10 and 20mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03mg/kg) injection. The cerebellum were then removed forcresylviolet staining, western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results showed that MDMA increased the number of cerebellar dark neurons.

Results: We observed that administration of CGS following MDMA, significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels.

Conclusion: These results indicated that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313443PMC
February 2015

Zingiber Officinale Alters 3,4-methylenedioxymethamphetamine-Induced Neurotoxicity in Rat Brain.

Cell J 2012 12;14(3):177-84. Epub 2012 Dec 12.

1. Research Institute for Islamic and Complementary Medicine (RICM), Tehran University of Medical Sciences, Tehran, Iran ; 2. Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Objective: The spice Zingiber officinale or ginger possesses antioxidant activity and neuroprotective effects. The effects of this traditional herbal medicine on 3,4-methylenedioxymethamphetamine (MDMA) induced neurotoxicity have not yet been studied. The present study considers the effects of Zingiber officinale on MDMA-induced spatial memory impairment and apoptosis in the hippocampus of male rats.

Materials And Methods: In this experimental study, 21 adult male Sprague Dawley rats (200-250 g) were classified into three groups (control, MDMA, and MDMA plus ginger). The groups were intraperitoneally administered 10 mg/kg MDMA, 10 mg/kg MDMA plus 100 mg/kg ginger extract, or 1 cc/kg normal saline as the control solution for one week (n=7 per group). Learning memory was assessed by Morris water maze (MWM) after the last administration. Finally, the brains were removed to study the cell number in the cornu ammonis (CA1) hippocampus by light microscope, Bcl-2 by immunoblotting, and Bax expression by reverse transcription polymerase chain reaction (RT-PCR). Data was analyzed using SPSS 16 software and a one-way ANOVA test.

Results: Escape latency and traveled distances decreased significantly in the MDMA plus ginger group relative to the MDMA group (p<0.001). Cell number increased in the MDMA plus ginger group in comparison to the MDMA group. Down-regulation of Bcl-2 and up-regulation of Bax were observed in the MDMA plus ginger group in comparison to the MDMA group (p<0.05).

Conclusion: Our findings suggest that ginger consumption may lead to an improvement of MDMA-induced neurotoxicity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584433PMC
March 2013

Evaluation of Bcl-2 Family Gene Expression in Hippocampus of 3, 4-methylenedioxymethamphetamine Treated Rats.

Cell J 2012 22;13(4):275-80. Epub 2011 Dec 22.

1. Department of Anatomical Sciences, Hamadan University of Medical Sciences, Hamadan, Iran.

Objective: 3,4-methylenedioxymethamphetamine (MDMA) is an illicit, recreational drug that causes cellular death and neurotoxicity. This study evaluates the effects of different doses of MDMA on the expression of apoptosis-related proteins and genes in the hippocampus of adult rats.

Materials And Methods: In this expremental study,a total of 20 male Sprague Dawley rats (200-250 g ) were treated with MDMA (0, 5, 10, 20 mg/kg i.p. twice daily) for 7 days. Seven days after the last administration of MDMA, the rats were killed. Bax and Bcl-2 genes in addition to protein expressions were detected by western blot and reverse transcriptionpolymerase chain reaction (RT-PCR).Results were analyzed using one-way ANOVA and p≤0.05 was considered statistically significant.

Results: Our results showed that MDMA caused dose dependent up-regulation of Bax and down-regulation of Bcl-2 in the hippocampus. There was a significant alteration in bcl-2 and bax genes density.

Conclusion: Changes in apoptosis-related proteins and respective genes relating to Bax and Bcl-2 might be involved in the molecular mechanism of MDMA-induced apoptosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584478PMC
March 2013

Synthesis and in-vitro cytotoxicity of poly-functionalized 4-(2-arylthiazol-4-yl)-4H-chromenes.

Arch Pharm (Weinheim) 2010 Jul;343(7):411-6

Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran.

A new series of 4-aryl-4H-chromenes bearing a 2-arylthiazol-4-yl moiety at the 4-position were prepared as potential cytotoxic agents. The in-vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated in comparison with etoposide, a well-known anticancer drug, using MTT colorimetric assay. Among them, the 2-(2-chlorophenyl)thiazol-4-yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2-(4-chlorophenyl)thiazol-4-yl moiety at the 4-position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF-7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC(50 )values less than 5 microM. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF-7 cells.
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http://dx.doi.org/10.1002/ardp.200900198DOI Listing
July 2010

Synthesis and antioxidant properties of substituted 3-benzylidene-7-alkoxychroman-4-ones.

Bioorg Med Chem Lett 2007 Dec 17;17(24):6764-9. Epub 2007 Oct 17.

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174, Iran.

A series of 3-benzylidene-7-alkoxychroman-4-one derivatives were synthesized and evaluated for their antioxidant activities. The antioxidant activity was assessed using three methods, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and thiobarbituric acid reactive substances (TBARS) assays. 3-Benzylidene-7-alkoxychroman-4-one derivatives bearing catecholic group on benzylidene moiety exhibited excellent antioxidant activity. Compounds having catechol moiety exhibited potent antioxidant activities in all tested methods and they were more active than the reference drug, Trolox.
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http://dx.doi.org/10.1016/j.bmcl.2007.10.034DOI Listing
December 2007
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