فهرست مطالب

Pharmaceutical Research - Volume:15 Issue: 3, Summer 2016

Iranian Journal of Pharmaceutical Research
Volume:15 Issue: 3, Summer 2016

  • تاریخ انتشار: 1395/08/16
  • تعداد عناوین: 35
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  • Amirreza Jalilian, Davood Beiki Pages 257-259
  • Hamid Reza Moghimi, Farshad Hoseini Shirazi, Mostafa Saffari Pages 261-267
    Gene therapy is in its development stage as a novel method for cancer treatment. Liposomes look promising as gene delivery vectors; however, investigations have shown that these vesicles are not doing well in some cases. It was decided here to investigate the possibility of augmentation of liposomal gene delivery by chemical penetration enhancers.
    Cationic liposome containing antisense oligonucleotide (AsODN) against lung cancer was prepared by ethanol injection method. Liposomal cineole and limonene (as enhancers) were prepared by film hydration method. Isopropyl myristate (IPM) was also investigated as penetration enhancer. Liposomes were evaluated for their size, zeta potential and encapsulation efficiency. Cancer cells (A549) were pretreated with liposomal terpenes prior to treatment with liposomal antisense or scrambled oligonucleotide. Cell viability was evaluated by MTT assay.
    Oligonucleotide -containing liposome showed particle size of about115 nm and zeta potential of 0.6 mV. Liposomal cineole significantly (P
    Keywords: Liposomal gene delivery, Penetration enhancer, Isopropyl myristate, Cineole, Limonene
  • Xiaoyun Zhang, Hua Qiao, Ying Chen, Lin Li, Huxiong Xia, Yanbin Shi Pages 269-282
    Low molecular weight heparin-modified isoliquiritigenin-loaded solid lipid nanoparticle (LMWH-ISL-SLN) was developed for injective application.
    The morphological observation, particle diameter and zeta potential of LMWH-ISL-SLN were characterized using transmission electron microscopy (TEM) and a Malvern Zetasizer. Its entrapment efficiency (EE) and drug loading (DL) were determined by ultracentrifuge. The in vitro release experiments were performed by dialysis technique. The cytotoxic effects of LMWH-ISL-SLN on Hep-G2 cell lines were determined using an MTT assay. Pharmacokinetic and tissue distribution studies were conducted in kunming mice after intravenous administration of LMWH-ISL-SLN.
    The average drug entrapment efficiency for LMWH-ISL-SLN was (99.80 ± 3.27) %, drug loading was (18.68 ± 1.51) %, mean particle size was (217.53 ± 4.86) nm and zeta potential was (–18.24 ± 2.47) mV. The in vitro release experiments demonstrated isoliquiritigenin release from LMWH-ISL-SLN was in line with Weibull’s distribution law. Hemolysis test and dose-related toxic effects proved that LMWH-ISL-SLN was a safe and non toxic product when given by intravenous injection. The pharmacokinetics results of LMWH-ISL-SLN showed that the area under the concentration-time curve (AUC0-∞) of LMWH-ISL-SLN was greater than that for the isoliquiritigenin solution in plasma. Tissue distribution study indicated that ISL were mainly distributed in the liver and lung.
    In conclusion, low molecular weight heparin-modified SLN system is a promising carrier for the intravenous delivery of ISL.
    Keywords: Low molecular weight heparin, Isoliquiritigenin, Solid lipid nanoparticle, Sustained release, Pharmacokinetics
  • Mohsen Sadeghi, Fariba Ganji, Seyyed Mojtaba Taghizadeh, Bahram Daraei Pages 283-294
    Here we report a novel approach for preparation of a 6-day transdermal drug delivery system (TDDS) as treatment for mild to moderate Alzheimer’s disease. The spray drying method was used to prepare microparticles containing the anti-Alzheimer drug. The content of the drug was determined by High Performance Liquid Chromatography (HPLC) method. The morphology and size range of the microparticles were determined. The stability of rivastigmine at high temperature was confirmed using FTIR analysis as well as a validate HPLC assay. The obtained results show that the drug was stable at high temperatures with 7 to 42% loading in the microparticles, and the higher drug concentrations of the solution injected into the spray dryer resulted in increase of the drug loading, surface drug and microparticles distortion. The TDDS containing the microparticles was also prepared with microparticle to dry adhesive ratios of 5, 10 and 15% using acrylic adhesive. Based on adhesion properties of the patches, gained from the probe tack and the peel adhesion 180° tests, and the 15% patch by having more drug content per unit area of the patch, and still having similar adhesion properties was compared to the microparticles-free patch of 5.1% Rivastigmine salt (equivalent to the drug content of the 15% patch) from the permeation point of view by using Franz cell diffusion over 6 days. The drug permeation rate from the microparticle-free patch was slower than the 15% microparticles patch, which is the result of crystallization of Rivastigmine salt in the acrylic adhesive.
    Keywords: Spray drying, Transdermal patch, Rivastigmine, Drug, in, adhesive, Chitosan microparticles
  • Darinka Gjorgieva Ackova, Katarina Smilkov, Emilija Janevik, Ivanovska Pages 295-302
    Radioimmunotherapy (RIT) of Non-Hodgkin’s lymphoma (NHL) is said to be more advantageous compared to unlabelled therapeutic antibodies. To this date, radiolabelled murine anti-CD20 mAbs, Zevalin® and Bexxar® have been approved for imaging and therapy. A preparation containing rituximab, chimeric mAb radioimmunoconjugate suitable for Lu-177 labeling, could provide better imaging and therapeutic profile at the same time. This study was conducted to evaluate prepared lyophilized formulations of two rituximab immunoconjugates, intended for immediate Lu-177 labeling, for imaging and therapy.
    The characterization of the conjugates and demonstration of the integrity of the protein and purity after conjugation and lyophilization was performed by SDS-PAGE, FT-IR and MALDI-TOF-MS. The results showed preserved antibody structure and average of 6.1 p-SCN-Bn-DOTA and 8.8 p-SCN-Bn-DTPA groups per antibody molecule which is suitable for successful labeling. These results support the possibility of developing a “ready-to-label” rituximab immunoconjugates for NHL imaging/therapy.
    Keywords: Rituximab, Lyophilized formulation, p, SCN, Bn, DOTA, p, SCN, Bn, DTPA
  • Mandana Amiri, Hamideh Imanzadeh Pages 303-311
    The adsorption processes of amlodipine onto hydrophilic carbon nanoparticles (Emperor 2000TM) are investigated. The significant increase in voltammetric responses for pre-adsorbed amlodipine compared with those for solution confirms high affinity of amlodipine to carbon nanoparticles (possibly due to π-π stacking interaction between aromatic rings of amlodipine and surface-sulfonated carbon nanoparticles). To obtain the optimum of adsorption conditions, the effects of pH, agitation rate, and adsorption time are investigated. Under differential pulse voltammetry conditions, the peak current for the oxidation of amlodipine shows two linear relationships with concentration in the range from 1000 μM to 10.0 μM and 10.0 μM to 10.0 nM. The limit of detection is estimated to be 1.0 nM. Determination of amlodipine in real samples such as human serum and commercial tablets is demonstrated.
    Keywords: Amlodipine, Carbon nanoparticles, Voltammetric sensor, Analysis
  • Alireza Aliabadi, Ahmad Mohammadi, Farani, Samira Soltani Darbandi Pages 313-320
    Patients with Alzheimer's disease have cognitive deficits, impaired long-term potentiation and learning and memory. A progressive reduction in cholinergic neurons in some areas of the brain such as cortex and hippocampus is related to the deficits in memory and cognitive function in Alzheimer’s disease (AD). In the current project a new series of phthalimide derivatives were synthesized. Phthalic anhydride was reacted with 4-aminobenzoic acid in the presence of triethylamine under reflux condtion. Then, the obtained acidic derivative was utilized for preparation of final compounds via an amidation reaction through a carbodiimde coupling reaction. Anti-acetylcholinesterase activity of synthesized derivatives was assessed by Ellman's test. Compound 4g in this series exhibited the highest inhibitory potency (IC50 = 1.1 ± 0.25 µM) compared to donepezil (IC50 = 0.41 ± 0.12 µM) as reference drug.
    Keywords: Synthesis, Phthalimide, Acetylcholinesterase, Alzheimer
  • Sohrab Ghanei Ghoshkaneh, Hossein Eshghi, Mohammad Saadatmandzadeh Pages 321-327
    Objective(s)
    In recent years, the chemistry of 2-chloroquinoline-3-carbaldehydes have received considerable attention owing to their synthetic and effective biological importance which exhibits a wide variety of biological activity, N1,N4-bis((2-chloroquinolin-3-yl)methylene)benzene-1,4-diamine derivatives that synthesized from 2-chloroquinoline-3-carbaldehydes may have biological effects. As the inhibitor of AKT1 (RAC-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT1), the aforementioned compounds may have implication in preventing complications of cancers.
    Materials And Methods
    A group of N1, N4-bis ((2-chloroquinolin-3-yl) methylene) benzene-1, 4-diamine derivatives (3a-3i) (H, 6-Me, 6-OMe, 6-OEt, 6-Cl, 7-Me, 6-Et, 6-Isopropyl, 7-Cl) were synthesized, and theoretically evaluated for their inhibitory as Potential Human AKT1 Inhibitors via docking process. The docking calculation was done in GOLD 5.2.2 software using Genetic algorithm.
    Results
    Compounds 3b (6-Me) and 3d (6-OEt) showed the best inhibitory potency by GOLD score value of 113.76 and 107.58 respectively.
    Discussion
    Some of the best models formed strong hydrogen bonds with Asn 49, Lys 220, Ser 157, Arg 225 and Trp 76 via quinoline moiety and nitrogen of quinolone ring (Figure 1). pi-pi interaction between Lys 220, Trp 76, Tyr 224, Arg 225, Ile 80, and Asn 49 quinoline moiety was one of the common factor in enzyme-inhibitor junction.
    Conclusion
    It was found that both hydrogen bonding and hydrophobic interactions are important in function of biological molecules, especially for inhibition in a complex.
    Keywords: AKT1 Inhibitors, cancer, Docking Analysis, Heterocyclic compound, Quinoline derivatives.
    Keywords: AKT1 Inhibitors, cancer, Docking Analysis, Heterocyclic compound, Quinoline derivatives
  • Xinran Bao, Han Liao, Jiao Qu, Yong Sun, Xin Guo, Enxia Wang, Yuhong Zhen Pages 329-335
    Quercetin, a ubiquitous flavonol, represents a promising leading drug for development of new chemotherapeutic agents. However, its limited cytotoxicity to cancer cells hampers its clinical use. In order to obtain novel quercetin derivatives with superior cytotoxicity, seven alkylated quercetin derivatives were synthesized. Solubility of these derivatives was determined by turbidimetry. Cytotoxicity of the high-soluble derivatives against MCF-7 cells and caco-2 cells was determined using MTT assay. Among these seven products, 7-O-butylquercetin had the highest solubility in DMEM medium and 7-O-geranylquercetin had the most potent cytotoxicity. Further study on cytotoxicity of 7-O-geranylquercetin on NCI-H446, A549, MGC-803 and SGC-7901 cell lines revealed potential antiproliferative effects. The 7-O-geranylquercetin is a broad spectrum cytotoxic agent and it may be a promising leading drug for cancer chemotherapy.
    Keywords: Quercetin derivatives, Cytotoxicity, Selective alkylation
  • Enayatollah Sheikhhosseini, Saeed Balalaie, Mohammadali Bigdeli Pages 337-342
    A new biological active hexapeptide of C-terminal of nocistatin, contains Glu-Gln-Lys-Gln-Leu-Gln sequence was synthesized according to solid phase peptide synthesis on the surface of 2-chloro tritylchloride resin and using fmoc-protected amino acids in the presence of TBTU (O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyl uranium tetrafluoroborate) as a coupling reagent. Then, amidation of the C-terminus of peptides was carried out using NH4Cl and alkyl ammonium chloride (RNH3Cl) in the presence of TBTU and a tertiary amine (DIPEA) as the base at room temperature in good to high yields. Cleavage of the desired peptides from the surface of the resin after the addition of TFA (1%) provided the protected peptides. All of the products were purified using preparative HPLC and structures were assigned according to MALDI-mass spectrometry data.
    Keywords: Solid phase peptide synthesis, Nocistatin, Amidation, C, Terminal amidated peptides
  • Aazam Monfared, Zohreh Esmaeeli Pages 343-367
    The anticoagulant racemic warfarin is synthesized by the Michael addition of 4-hydroxycoumarin with benzalacetone in the present of equimolar amounts of imidazolium based ionic liquids [bmim] BF4 and [bmim] Br and other reaction solvents such as H2O, pyridine and ammonia in five different tests. Also synthesis of a derivative of warfarin (2-methyl-4-phenyl pyrano [3, 2-c] chromen-5(4H)-one) under solvent-free condition is reported. In this paper, we show the potential that ionic liquid have for the development of green methods for the formation of the C-C bond by reaction condensations without catalysts and organic solvents. A ¡green method, according to the well-known principles, must reduce or eliminate the use or generation of unsafe substances. The work-up procedures were fairly simple and the products dont require further purification.
    Keywords: Michael addition, Ionic liquid, warfarin, close, ring
  • Danial Shamshirian, Mostafa Erfani, Davood Beiki, Maliheh Hajiramazanali, Babak Fallahi Pages 349-360
    Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target for the development of α-MSH peptide based imaging and therapeutic agents. In this work a new lactam bridge α-MSH analogue was synthesized and radiolabeled with 99mTc via HYNIC chelator and tricine as co-ligand. Also, stability in human serum, receptor bound internalization and tissue biodistribution in tumor bearing nude mice were thoroughly investigated. Radiolabeling with 99mTc was performed at high specific activities (163MBq/nmol) with an acceptable labeling yield (>98%). The radioligand showed specific internalization into B16/F10 cells (13.35 ± 0.9% at 4 hours). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor positive organ so that after 4 hours the tumor uptake was 4.51±0.11 % ID/g. Predominant renal excretion pathway with a highest accumulation of activity in tumor was observed for this radiopeptide. Obtained results show that the new designed labeled peptide conjugate can be a suitable candidate for diagnosis of metastatic melanomas.
    Keywords: α, MSH, 99mTc, Tricine, HYNIC, Radiopeptide
  • Rouhollah Karami, Osboo, Ramin Miri, Katayoun Javidnia, Farzad Kobarfard Pages 361-368
    The antibiotic residues in milk are a well-known serious problem and pose several health hazards to consumers. We have described a simple, rapid, and inexpensive DLLME-HPLC/UV technique for the extraction of chloramphenicol and florfenicol residues in milk samples. Under the optimum conditions, linearity of the method was observed over the range 0.02-0.85 µg/L with correlation coefficients > 0.999. The proposed method has been found to have a good limit of detection (signal to noise ratio = 3) for chloramphenicol (12.5 µg/kg) and florfenicol (12.2 µg/kg), and precision with relative standard deviation values under 15% (RSD, n = 3). Good recoveries (69.1–79.4 %) were obtained for the extraction of the target analytes in milk samples. This simple and economic method has been applied for analyses of 15 real milk samples. Among all samples only one of them was contaminated to florfenicol; 62.4 µg/kg and contamination to chloramphenicol was not detected.
    Keywords: DLLME, chloramphenicol, florfenicol
  • Alptug Atila, Bilal Yilmaz, Yucel Kadioglu Pages 369-378
    This paper describes two rapid, sensitive and specific methods for the determination of fulvestrant in pharmaceutical preparations by high performance liquid chromatography (HPLC) and linear sweep voltammetry (LSV). HPLC method was used to study the degradation behaviour. Fulvestrant was subjected to degradation under the conditions of hydrolysis (acid and alkali), oxidation (30% H2O2). The linearity was established over the concentration range of 5-50 m g mL-1 for LSV and 0.5-20 mg mL-1 for HPLC method. The intra- and inter-day relative standard deviation (RSD) was less than 3.96 and 3.07% for LSV and HPLC, respectively. Limits of quantification were determined as 5.0 and 0.50m g mL-1 for LSV and HPLC, respectively. No interference was found from tablet excipients at the selected assay conditions. The methods were applied for the quality control of commercial fulvestrant dosage form to quantify the drug and to check the formulation content uniformity.
    Keywords: Fulvestrant, LSV: HPLC, Stability indicating, Validation
  • Seyed Karim Hassaninejad, Darzi, Abdolraouf Samadi, Maybodi, Seyed Mohsen Nikou Pages 379-391
    Resolution of binary mixtures of theophylline (THEO), montelukast (MKST) and loratadine (LORA) with minimum sample pretreatment and without analyte separation has been successfully achieved by multivariate spectrophotometric calibration, together with partial least-squares (PLS-1), principal component regression (PCR) and hybrid linear analysis (HLA). Data of analysis were obtained from UV–Vis spectra of three compounds. The method of central composite design was used in the ranges of 2–14 and 3–11 mg L–1 for calibration and validation sets, respectively. The models’ refinement procedure and their validation were performed by cross-validation method. The minimum root mean square error of prediction (RMSEP) was 0.173 mg L−1 for THEO with PCR, 0.187 mg L–1 for MKST with PLS1 and 0.251 mg L–1 for LORA with HLA techniques. The limit of detection was obtained 0.03, 0.05 and 0.05 mg L−1 by PCR model for THEO, MKST and LORA, respectively. The procedure was successfully applied for simultaneous determination of the above compounds in pharmaceutical tablets and human plasma. Notwithstanding the spectral overlapping among three drugs, as well as the intrinsic variability of the latter in unknown samples, the recoveries are excellent.
    Keywords: UV, Vis spectrophotometry, Multivariate calibration 1, Theophylline, Montelukast, Loratadine
  • Mehmet Boga, Abdulselam Ertas, Mustafa Abdullah Yilmaz, Murat Kizil, Bircan Ceken, Nesrin Hasimi, Tugba Yilmaz Ozden, Serpil Demirci, Ismail Yener, Ozcan Deveci Pages 393-405
    This paper is the first phytochemical and ABTS cation radical decolorisation activity, cupric reducing antioxidant capacity, anticholinesterase and DNA damage protection effect of endemic Verbascum pinetorum (Boiss.) O. Kuntze. Phenolic profile of V. pinetorum were qualified and quantified by UHPLC-ESI-MS/MS analysis. Malic acid (47250.61±2504.28 µg/g) and luteolin (7651.96±527.98 µg/g) were found as most abundant compounds for metanol and acetone extracts, respectively. Fatty acid and essential oil compositions were determined by GC-MS analysis. The main components of fatty acid were found to be palmitic (27.1%) and stearic (22.1%) acids. The main compounds of the essential oil were cineole (16.9%) and α-selinene (16.4%). The acetone extract was found to be more active than BHT used as a standard in β-carotene-linoleic acid test system. In DPPH free radical scavenging activity, the acetone and methanol extracts showed higher activity than BHT at all tested concentrations. The acetone, methanol and water extracts showed strong inhibition while the acetone extract showed better activity than BHT and α-tocopherol which were used as standards in ABTS cation radical scavenging and cupric reducing antioxidant capacity assays, respectively. All extracts were found to be inactive in antialzheimer activity. The acetone extract exhibited moderate antimicrobial activity against C. albicans. The methanol extract of V. pinetorum were found no significant effect on DNA cleavage protection.
    Keywords: Verbascum pinetorum, fatty acid, essential oil, antioxidant, anticholinesterase
  • Zohreh Mashak, Hadi Jafari Sohia, Ali Heshmati, Amir Sasan Mozaffari Nejad Pages 407-411
    This study was carried out to detect the presence of aflatoxin M1 (AFM1) in 30 UHT flavored milk samples in Karaj, Alborz province of Iran. High-performance liquid chromatography (HPLC) was applied to analyse AFM1 in the samples. Result showed that aflatoxin M1 was detected in all the UHT flavored milk samples, the concentration of AFM1 was ranged from 0.015 to 0.14 µg/kg. Also, 10 samples (33.3%) was contaminated with more than 0.05 µg/kg of European Union regulations for aflatoxin M1. While, according to proposed Iranian national standard and FDA (0.5 µg/kg), none of sample has not contaminated more than the maximum tolerable concentrations of AFM1. This is the first report discovering that UHT flavored milk is a important contributor to the dietary intake of AFM1 in Iran.
    Keywords: Aflatoxin M1, UHT flavored milk, HPLC, Iran
  • Nima Razzaghi, Asl, Ramin Miri, Omidreza Firuzi Pages 413-420
    Cancer is a leading cause of death worldwide. Despite the availability of several chemotherapeutic drugs, there is still a great need for more efficient agents for a better management of cancer. In this contribution, a series of 11 DHPs (4a, 4b & 7a-i) were synthesized and evaluated for their cytotoxic effect against MCF-7, LS180, and MOLT-4 cancer cell lines using MTT assay. Synthesized 2,6-dimethyl-3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridines exhibited different potencies ranging from weak to good cytotoxic activities, while no activity could be recorded for 1,4-bis(2,6-dimethyl-3,5-dimethoxylcarbonyl-1,4-dihydropyridine-4-yl) benzene compounds (4a & 4b). Tested DHP derivatives were more potent against MOLT-4 cells, when compared to LS180 and MCF-7 cells. Compounds 7d (IC50=28.5±3.5 µM), 7a (IC50=29.7±4.7 µM) and 7a (IC50=17.4±2.0 µM) were the most potent derivatives against MCF-7, LS180 and MOLT-4 cells, respectively. It appeared that the introduction of N-thiazolyl carbamoyl group at the C3 and C5 positions of DHP ring enhanced the cytotoxic potential of these derivatives (compounds 7a-e). The findings of this study suggest that some of the thiazole substituted 1,4-DHPs may be candidates for further modifications towards the discovery of potent antitumoral agents.
    Keywords: Synthesis, Dihydropyridine, Anticancer activity, Modeling, MTT assay
  • Mahdi Mashhadi Akbar Boojar, Shahram Ejtemaei Mehr, Mahsa Hassanipour, Masoud Mashhadi Akbar Boojar, Ahmad Reza Dehpour Pages 421-433
    Ceramide as a second messenger is a key regulator in apoptosis and cytotoxicity. Ceramide-metabolizing enzymes are ideal target in cancer chemo-preventive studies. Neutral sphingomyelinase (NSMase), acid ceramidase (ACDase) and glucosyl ceramide synthase (GCS) are the main enzymes in ceramide metabolism. Silymarin flavonolignans are potent apoptosis inducers and silibinin is the most active component of silymarin. This study evaluated the effects of silybin A, silybin B and their 3-O-gallyl derivatives (SGA and SGB) at different concentrations (0-200 micro molar) on ceramide metabolism enzymes in Hep G2 hepatocarcinoma cell line. Cell viability, caspase-3 and 9 activities, total cell ceramide and the activities of ACDase, NSMase and GCS were evaluated. Under silibinin derivatives treatments, cell viability decreased and the activities of caspase-3 and 9 increased in a dose dependent manner among which SGB was the most effective one (P
    Keywords: Ceramidase, Silymarin, Sphingomyelinase, Glucosyl ceramide synthase, Ceramide
  • Mahmood Barati, Mohammad Ali Faramarzi, Nastaran Nafissi, Varcheh, Mohammad Reza Khoshayand, Mohammad Hassan Houshdar Tehrani, Hossein Vahidi, Sina Adrangi Pages 435-440
    The objective of this study was to isolate halophilic bacteria with the ability to produce intracellular or extracellular L-asparaginase. A total number of 120 halophilic bacteria were isolated from 17 different saline habitats of Iran including salt lakes, wetlands, brine springs and deserts. Among these, 68 were able to grow in the presence of 1.5 M NaCl and 52 demonstrated the ability to grow in the selection medium containing 3.5 M NaCl. None of the isolates appeared to produce appreciable amounts of extracellular L-asparaginase. Among the isolates that produced intracellular L-asparaginase, 5 moderate and 1 extreme halophiles were selected for further study based on their observed activity level. The moderately halophilic isolates were shown to belong to the genus Halomonas while the extreme halophile was identified as a member of the genus Aidingimonas.
    Keywords: Screening, halophile, L, asparaginase, Halomonas, Aidingimonas
  • Maryam Azimi, Nastaran Nafissi, Varcheh, Mohammad Ali Faramarzi, Reza Aboofazeli Pages 441-452
    The aim of this study was to develop a microemulsion system as a medium for laccase-catalyzed reactions. Phase behavior studies were conducted by constructing partial pseudo-ternary phase diagrams for systems comprising of cetyltrimethylammonium bromide (CTAB), various organic solvents as the oil phase (i.e., hexane, cyclohexane, heptane, octane, isooctane, toluene, isopropyl myristate), two co-surfactants (i.e., 1-butanol and 1-hexanol) and citrate buffer solution, at various surfactant/co-surfactant weight ratios (Rsm). A monophasic, transparent, non-birefringent area (designated as microemulsion domain) was seen to occur in some phase diagrams along the surfactant/organic solvent axis, the extent of which was dependent mainly upon the nature of co-surfactant and Rsm. On each phase diagram, three different water-in-oil microemulsion systems with less than 50 wt% surfactant mixture and less than 20 wt% of aqueous phase were selected for laccase loading and activity measurements. Results revealed that the catalytic activity of laccase in CTAB-based w/o microemulsions decreased considerably, compared with its activity in the buffer solution, the extent of which depended upon the type of component and their compositions in the microemulsions. It was suggested that the conformational changes due to the electrostatic interactions between the cationic head group of CTAB and the negative enzyme might be the reason for the reduction of laccase activity, once entrapped in the microemulsion.
    Keywords: Laccase, Enzyme activity, W, o microemulsions, Phase diagram, CTAB
  • Saly Gheda, Hala El, Adawi, Nehal El Deeb Pages 453-457
    Hepatitis C virus (HCV) has infected 3% of the population worldwide and 20% of the population in Egypt. HCV infection can lead to hepatocellular carcinoma and death. The presently available treatment with interferon plus ribavirin, has limited benefits due to adverse side effects. Seaweeds have become a major source of new compounds to treat viral diseases. This work aimed to study the effect of four species of seaweeds as anti- HCV. The inhibition of lipid peroxidation was measured by evaluating the ability of seaweed extracts to scavenge the free radicals. The HepG2 cells were infected with the HCV and treated with each seaweed polysaccharide. Inhibition of viral replication was detected using the Real Time PCR (RT) qPCR. To explain the mode of the seaweed action on HCV, three modes of virus infections and seaweed polysaccharide treatments were applied. All treatments had the ability to inhibit the HCV with priority to Laurencia obtusa (82.36%), while the potentiality to scavenge the free radicals reached up to 81.5 % with the Sargassum vulgare. Seaweed polysaccharide extracts may be helpful in exploring further gateways for antiviral therapy against HCV.
    Keywords: seaweeds_polysaccharides_hepatitis C virus_free radicals_PCR
  • Jamal Shamsara, Ahamad Shahir, Sadr Pages 459-469
    Design of selective cyclooxygenase-2 (COX-2) inhibitors is still a challenging task because of active site similarities between COX isoenzymes. To help with this issue, we tried to generate a 3D-QSAR (3 dimensional quantitative structure activity relationship) model that might reflect the essential features of COX-2 active sites. Compounds in a series of resveratrol derivatives inhibitors with reported biological activity against COX-2 were used to construct a predictive comparative molecular similarity indices (CoMSIA) model. A CoMSIA model with acceptable internal and external predictability was developed and employed to design new not yet synthesized molecules with improved activity and selectivity toward COX-2. Finally, molecular docking of the inhibitors in COX-2 active site demonstrated the possible ability of proposed compounds to inhibit COX-2, selectively.
    Keywords: 3D, QSAR, COX, 2, COMSIA, Inhibitors, Resveratrol
  • Mahboubeh Taherkhani Pages 471-481
    The aim of this study was to determine the chemical constituents, antimicrobial, cytotoxicity, mutagenic and anti-mutagenic activities of the essential oil of Artemisia ciniformis Krasch. & Popov ex Poljakov, against important bacterial pathogens and human cells which were unknown before. In vitro cytotoxicity was measured using a modified MTT assay on normal human lymphocytes and tumor HeLa cells. The mutagenic and antimutagenic activities of the oil were evaluated using the Salmonella typhimurium tester strains TA98 and TA100, together with nitrofluorene for TA98 and sodium azide for TA100 without (-S9) metabolic activation, and 2-aminoantracene for TA98 and TA100 with metabolic () activation. Oxygenated monoterpenes especially camphor (30.21 %), 1,8-cineole (23.7 %) and trans-Pinocarveol (12.28 %) were the major components of the oil of A. ciniformis. Bactericidal kinetics of this oil indicated that Acinetobacter baumannii is the most vulnerable one (MIC = 0.02 mg/ml, MBC = 0.04 mg/ml, Dvalue = 3.57 min). The oil displayed an excellent cytotoxic action toward the human tumor cell line (IC50 = 19.64 µg/ml). The oil of A. ciniformis showed excellent antimutagenicity effect on the 2-nitrofluorene, in the strain of S. typhimurium TA98, without the presence of metabolic activation.
    Keywords: Artemisia ciniformis, antimicrobial, Cytotoxicity, Antimutagenic, HeLa, lymphocytes cells
  • Hassan Malekinejad, Amir Amniattalab, Aysa Rezabakhsh Pages 493-500
    This study aimed to investigate the potency of silymarin (SMN) and melatonin (MEL) on restoring the pancreatic β cells in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into five groups, including: control (C), untreated diabetic (D), SMN-treated diabetic (50 mg/kg, orally), MEL-treated diabetic (10 mg/kg, i.p.), and SMN plus MEL-treated diabetic rats. Diabetes was induced by injection of STZ (50 mg/kg, i.p.). The blood glucose and insulin levels were measured. After the 28 days treatment period, antioxidant status was analyzed by determination of total antioxidant capacity (TAC) in the liver and serum. The histopathological changes in the pancreatic islets were examined by histochemical staining and enumeration of βcells. Although none of the test compounds reduced the blood glucose level to normal concentration, however SMN alone and in combination with MEL was able to decline it significantly (P
    Keywords: Antioxidant status, cell restoring, Melatonin, Silymarin, Streptozotoci, induced diabetes
  • Filiz Bakar, Songul Karakaya, Fatma Gul Delimustafaoglu Bostanlik, Ceyda Sibel Kiilic Pages 501-504
    Ferulago W. Koch. (Apiaceae) genus is represented by approximately 50 taxa throughout the world. Ferulago species are known as “Çakşır” or “Çağşır” in Turkey and mostly known for their aphrodisiac effects. However recent reports emphasize the activity of various Ferulago species against cancer, as well. The aim of this study was to investigate the effect of lyophilized extract of F. mughlea Peşmen, a species endemic for Turkey, on cancer cell proliferation. For this purpose human prostate (PC-3) and colorectal (SW-480) carcinoma cells were used to evaluate the antiproliferative effects of Ferulago W. Koch and the measurements were performed via MTT test. Lyophilized extracts obtained from aerial parts and the roots exhibited potent inhibitor effects on cell proliferation. The aerial part of plant inhibited the proliferation of SW-480 cell at 48th hour with a 0.119 mg/ml IC50 value.
    Keywords: Ferulago, antiproliferative, cancer, prostate
  • Narayan Dolai, Aminul Islam, Pallab Kanti Haldar Pages 505-514
    The purpose of this investigation was to evaluate the antiproliferative and apoptogenic mechanistic studies of methanol extract of Anthocephalus cadamba (MEAC) on Dalton’s lymphoma ascites (DLA) cells treated mice. Determination of antiproliferative activity was performed by using different DLA cells (2×106 cells, i.p.) inoculated mice groups (n=12). Groups were treated for 14 consecutive days with MEAC at the doses of 200 and 400 mg/kg b.w. respectively. The mechanism of antiproliferation activity of MEAC was investigated through morphological studies by acridine orange (AO)/ethidium bromide (EB) double staining method. Comet assay was estimated to check the DNA damage induced apoptosis property. Furthermore, flow cytometry (FACS) was used to quantitatively detect the apoptotic rate by double labeling techniques using Annexin-V FITC/propidium iodide staining analysis and apoptotic proteins expression done by western blotting assay method. MEAC exhibited significant (p
    Keywords: Anthocephalus cadamba, DLA, Antitumor, Apoptosis
  • Seyed Ebrahim Sajjadi, Nader Pestechian, Mahnaz Kazemi, Mohammad Ali Mohaghegh, Ahmad Hosseini, Safa Pages 515-521
    Background
    Resistance to most antimalarial drugs has encouraged the development of novel drugs. An alternative source for discovering such drugs is natural products. Some Ferulago species are used in folk medicine for their sedative, tonic and anti-parasitic effects. Besides, coumarins isolated from this genus found to have in vitro anti-leishmanicidal effect. The present study is aimed to evaluate the in vivo antimalarial activity of Ferulago angulata (Schlecht.) Boiss. extract and suberosin epoxide, using suarian mice.
    Methods
    A rodent malaria parasite, Plasmodium berghei was used to inoculate healthy male Swiss Albino mice of age 6-8 weeks and weight 23-27 g. Hydro-alcoholic extract of F. angulata (20, 100, 300, 600 mg/kg) and suberosin epoxide suspension (10, 30, 50, 100 mg/kg) were administered subcutaneously. Parameters including percentage of parasitemia, suppression of parasitemia and mean survival time were determined using standard test such as peter٬s.
    Results
    Chemo-protective effects were exerted by the crude extract and suberosin epoxide. Maximum effect was observed with the larger doses of the crude extract and suberosin epoxide. Suberosin epoxide increased the survival time compared to chloroquine.
    Conclusion
    The results indicate that the plant has a promising anti-plasmodial activity against plasmodium berghei. Thus, it could be considered as a potential source of new antimalarial agents. Suberosin epoxide at the dose of 100 mg/kg possess relatively significant antimalarial effect. Chemical derivatization of the parent compound or preparation of the modified formulation is required to improve its systemic bioavailability.
    Keywords: Ferulago angulata, Suberosin epoxide, Plasmodium berghei, Antimalaria
  • Solmaz Asnaashari, Fariba Heshmati Afshar, Sedigheh Bamdad Moghadam, Abbas Delazar Pages 523-529
    Six extracts with different polarity from aerial parts and rhizomes of Eremostachys azerbaijanica Rech.f., were screened for their antimalarial properties by cell free 𝛽-hematin formation assay. Dichloromethane (DCM) extracts of both parts of plant showed significant antimalarial activities with IC50 values of 0.949 ± 0.061 mg/mL in aerial parts and 0.382 ± 0.011 mg/mL in rhizomes. Bioactivity-guided fractionation of the most potent part (DCM extract of rhizomes) by vacuum liquid chromatography (VLC) afforded seven fractions. Two fractions (100% Ethyl acetate (EtOAC) and 100% Methatol (MeOH)) showed considerable antimalarial activity with IC50 values of 0.335 ± 0.033 mg/mL and 0.403 ± 0.037 mg/mL, respectively.
    According to GC-MS analysis, sesquiterpenes, steroids and coumarines derivatives are the main constituents of the most potent fractions; therefore, it seems that the anti malarial activity of these fractions may be related to the presence of these types of compounds.
    Keywords: Antimalaria, Eremostachys azerbaijanica, Cell free assay, GC, MS
  • Eman Shawky Pages 531-535
    Amaryllidaceae is a well-known family for its high alkaloidal content. These alkaloids comprise a unique group of bases that have been found to occur in this family. The Amaryllidaceae alkaloids represent a large and still expanding group of isoquinoline alkaloids, the majority of which are not known to occur in any other family of plants This article reports on the phytochemical investigation of the alkaloidal content of the flowers of clivia nobilis cultivated in Egypt which resulted in the isolation of four alkaloids; lycorine with pyrrolo{de}phenanthridine nucleus (lycorine-type) which is the common alkaloid of the amaryllidaceae family, clivatine nobilisine, both with [2]benzopyrano (3,4-g) indole nucleus (lycorenine-type) and () 8-O-demethylmaritidine with 5,10b-ethanophenanthridine nucleus (crinine-type). Furthermore, the antimicrobial activity of the chloroform extract of the flowers of c. nobilis along with some of the isolated alkaloids has been studied.
    Keywords: Amaryllidaceae, alkaloids, Clivia nobilis flowers, antimicrobial
  • Shahnaz Bahadoria, Jamshid Salamzadehbc., Mohammad Kamalinejadd, Mohammad Reza Shams Ardekanie, Mansoor Keshavarzf, Arman Ahmadzadehg Pages 537-545
    This study was designed to explore the complementary effects of a combination formulation of olive oil, olive and fig fruits on RA remission indicators. A randomized controlled clinical trial was designed. Adult RA patients were randomly divided into two groups receiving routine Disease-modifying antirheumatic drugs (DMARDs) regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the Disease Activity Score with 28-joint counts based on Erythrocyte Sedimentation Rate (DAS28_ESR) were recorded. SPSS (version 22.0) software was used to analyze data, assuming p
    Keywords: Rheumatoid arthritis, Complementary medicine, Fig, Olive, DAS28, ESR
  • Mehrnoosh Shanaki Bavarsad, Taghi Golmohammadi, Arash Hossein, Nezhad, Reza Meshkani, Maani Beigy, Mahmoud Shirzad, Parvin Pasalar Pages 547-559
    Coronary artery disease (CAD) is the major cause of mortality and morbidity worldwide. The aim of this study was to explore the effect of resveratrol (RES) on Canonical β catenin/Wnt and forkhead box O (FOXO) pathways in CAD patients. We performed this study on 10 metabolic syndrome patients with three-vessel CAD and 10 sex-aged matched healthy subjects. The effects of RES on β-Catenin, manganese superoxide dismutase (MnSOD), and peroxisome proliferator-activated receptor delta (PPAR-δ) expression were evaluated in peripheral blood mononuclear cells (PBMCs) of participants. RES could increase the MnSOD expression in CAD patients (38%, p
    Keywords: Coronary artery disease, Resveratrol, Wnt signaling, FOXO
  • Yousef Rasmi, Maryam Majidinia, Mirhosssein Seyedmohammadzad, Mohammad Hasan Khademansari Pages 561-566
    Endothelial dysfunction which is manifested by the loss of nitric oxide bioavailability, is an increasingly recognized cause of cardiac syndrome X (CSX) and beta blockers are used for the treatment of this syndrome. Thus, the aim of this study was to investigate effects of metoprolol, as a beta blocker, on endothelial function in CSX patients.
    The study included 25 CSX patients (20 female/ 5 male, mean age: 55.3610.31 years) who received metoprolol (50 mg BID) for one month. In addition, 25 healthy controls (20 female/ 5 male, mean age: 54.329.27 years) were enrolled. Levels of endothelin-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in controls and CSX patients were measured , both at the baseline and after the treatment, by the enzyme-linked immunosorbent assay. In CSX patients, at the baseline, levels of E-selectin and VCAM-1 were significantly higher than those of the controls. In addition, levels of these biomarkers in CSX patients after the treatment significantly decreased compared to the baseline. In spite of similar tendency, these differences were not significant for endothelin-1. In conclusion, metoprolol therapy improves endothelial function. Thus, it may be a suggested choice for CSX treatment. However, further studies are needed to confirm the clinical significance of metoprolol therapy for CSX patients.
    Keywords: metoprolol, endothelial function, cardiac syndrome X
  • Golbarg Ghiasi, Arash Rashidian, Abbas Kebriaeezadeh, Jamshid Salamzadeh Pages 567-571
    The impact of the international sanctions on the Central Bank of Iran in 2013 and also accessibility of medicines in this country have received a lot of media coverage. In this study we used the data collected from a group of pharmacies all located in Tehran to assess the potential effects of the banking sanctions on access to asthma medicines. Data were collected from forty community pharmacies in Tehran, using a standard methodology proposed by the WHO and Health Action International. Data were collected in two stages: first before the sanctions were made against the banking system in the summer of 2012, and second after they were in effect in the summer of 2013, and they were analyzed using univariate analysis techniques. Several imported medicines were already in shortage during 2012. As a result of the sanctions, the availability of both imported and locally manufactured asthma medicines decreased by 19% and 42%, respectively. While before the height of the sanctions 60% of the pharmacies could provide all the essential asthma medicines, this number reduced to 28% after the sanctions (p-value: 0.003). While studies about “access to medicines” in Iran prior to 2011 were indicating appropriate access, our findings suggested that the availability of asthma medicines in community pharmacies was already less than ideal in 2012 and declined dramatically after the latest wave of the sanctions. Our findings show the important effects of the sanctions on availability of asthma medications in community pharmacies.
    Keywords: sanction, Availability, Asthma Medicines, pharmacies
  • Amir Mortazavian Pages 573-591
    Milk is an important component of a balanced diet and contains many valuable constituents. A considerable part of the milk healthbenefits is related to its proteins, not only for their nutritive value but also for their biological properties. Scientific evidence suggests that anticarcinogenic activities, antihypertensive properties, immune system modulation, and other metabolic features of milk, are affiliated with milk proteins (both the intact proteins and their derivatives). They could be beneficial to prevent, control and even treat some lifestyle-related diseases. In this article, the main health-related aspects of milk proteins, such as anticarcinogenic, immunomodulatory, antimicrobial, anticariogenic, antihypertensive, and hypocholesterolemic effects, are reviewed. Collectively, the findings indicate the effectiveness of milk proteins in reduction of the risk of cancers and cardiovascular diseases also improvement of overall health aspects.
    Keywords: Whey, Casein, Peptide, Health, Nutrition