فهرست مطالب

  • Volume:11 Issue: 3, 2016
  • تاریخ انتشار: 1395/04/15
  • تعداد عناوین: 10
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  • Mehran Mesgari Abbasi, Hadi Valizadeh, Hamed Hamishehkar, Parvin Zakeri, Milani* Pages 177-186
    P-glycoprotein (P-gp) is a trans-membrane drug efflux pump. Several drugs are P-gp substrates. Some drugs may affect the activity of P-gp by inhibiting its function, resulting in significant drug-drug interactions (DDIs). It is critical to understand which drugs are inhibitors of P-gp so that adverse DDIs can be minimized or avoided. This study investigated the effects of gliclazide, metformin, and pioglitazone on the function and expression of P-gp. Rhodamine 123 (Rh 123) efflux assays in Caco-2 cells and western blot testing were used to study in vitro the effect of the drugs on P-gp function and expression. The in situ rat single-pass intestinal permeability model was developed to study the effect of the drugs on P-gp function. Digoxin and verapamil were used as a known substrate and inhibitor of P-gp, respectively. Digoxin levels in intestinal perfusion samples were analyzed by high-performance liquid chromatography. Intestinal effective permeability (Peff) of digoxin in the presence of 0.1, 10, and 500 μM gliclazide, 100 and 7000 μM metformin, and 50 and 300 μM pioglitazone was significantly increased relative to the digoxin treated cells (P 0.05). It was found that gliclazide, metformin, and pioglitazone inhibited P-gp efflux activity in situ and down-regulated P-gp expression in vitro. Further investigations are necessary to confirm the obtained results and to define the mechanism underlying P-gp inhibition by the drugs.
    Keywords: Gliclazide, Intestinal permeability, Metformin, P, glycoprotein, Pioglitazone
  • Meysam Soleimani, Karim Mahnam, Hamid Mirmohammad, Sadeghi, Hojjat Sadeghi, Aliabadi, Ali Jahanian, Najafabadi* Pages 187-199
    p28 and NRC peptides are two anticancer peptides with various mechanisms have shown to be effective against breast cancer. Therefore, it seems that construction of a chimeric protein containing the two peptides might cause synergistic cytotoxic effects. However, since the two peptides bear opposite charges, production of a chimeric protein in which the two moieties do not intervene each other is difficult. In this study, our goal was to find a suitable peptide linker for the new chimeric protein in a manner that none of the peptides intervene the other’s function. We selected some linkers with different characteristics and lengths and created a small library of the chimeric proteins harboring these linkers. Homology modeling and molecular dynamic simulation revealed that (PA)5P and (EAAAK)3 linkers can separate the p28 and NRC peptides effectively. Thus, the chimeric protein linked with (PA)5P or (EAAAK)3 linkers might show synergistic and stronger anticancer effects than the separate peptide moieties because they could exert their cytotoxic effects freely which is not influenced by the other part.
    Keywords: NRC, p28, Linker, Salt Bridge, Homology modeling, Molecular Dynamic Simulation
  • Hassan Sadraei *, Gholamreza Asghari, Farzaneh Shahverdi Pages 200-209
    Dracocephalum kotschyi Boiss, a member of Labiatae family, is a native plant to Iran, which has been reported to have immunomodulatory, antihyperlipidemic and antispasmodic activities. The objective of this research was to study the antispasmodic and antidiarrhoeal activities of hydroalcoholic and hexane extracts of D. kotschyi in mice. Furthermore, the antidiarrhoeal and antispasmodic effect of apigenin, a flavonoid constituent of D. kotschyi, was also studied. Hydroalcoholic and hexane extracts were obtained from aerial part of D. kotschyi using percolation method. Antispasmodic effect of the test compounds was assessed by measurement of small intestine transit following oral administration of a charcoal meal. Diarrhoea was induced by administration of either castor oil (0.5 ml) or magnesium sulphate (MgSO4) (10% w/v solution). Both the hydroalcoholic and hexane extracts of D. kotschyi (10 and 20 mg/kg) reduced the intestinal charcoal meal transit. Loperamide (2 mg/kg) and apigenin (2 and 10 mg/kg) inhibited intestinal movement of the charcoal meal and also inhibited castor oil and MgSO4-induced diarrhoea. The hydroalcoholic and hexane extracts of D. kotschyi (10 and 20 mg/kg) also significantly inhibited the castor oil and MgSO4 induced diarrhoea in mice in comparison with the vehicle-treated control groups. This study confirms that both the hydroalcoholic and hexane extracts of D. kotschyi has antispasmodic and antidiarrhoeal properties in vivo and could be a suitable remedy for treatment of gastrointestinal disorders in which smooth muscle spasm and/or diarrhoea plays a significant roles.
    Keywords: Dracocephalum kotschyi, Antispasmodic, Antidiarrhoeal, Apigenin, Ileum transit
  • Leila Hosseinzadeh, Alireza Aliabadi, Masoud Kalantari, Abolfazl Mostafavi, Marzieh Rahmani Khajouei* Pages 210-218
    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.
    Keywords: Quinazolinone, Thiazole, Cytotoxicity
  • Nnadi Charles Okeke*, Udeani Theophilus Kc, Ugwu Linus Onyebuchi Pages 219-226
    This research established the scientific bases for the folkloric use of the neglected Dialium guineense fruit coat in wound and microbial infection management in Nigeria. The phytochemical analysis of the crude extract, fractions and sub-fractions was performed by standard methods. Agar well diffusion protocol was adopted for the antimicrobial assay while the wound healing properties was determined by full thickness skin excision wound model. Phytochemical analysis showed high relative proportion of alkaloids (6.05 ± 0.98 %), saponins (3.91 ± 0.02 %) and tannins (1.86 ± 0.05 %). The only active fraction (DF) and sub-fraction (DF-5) were effective against Gram-positive (inhibition zone diameters, IZDs, 8-10 mm and 11-15 mm) and Gram-negative (IZDs, 15-19 mm and 16-21 mm) bacteria and fungi (6-8 mm) compared with 20-24 mm and 18-19 mm of the standard (ciprofloxacin) respectively. Fifty mg/kg of the DF-5 showed nearly equal percentage wound healing post-surgery days to Cicatrin®. The 50 mg/kg dose of DF and DF-5 showed more than 50 % wound healing at 10th day post-surgery, 50 mg/kg crude extract showed 54 % on day 14 while distilled water showed 56 % wound healing on day 17 with no sign of infection in all animal groups. All the treatments were significantly (P
    Keywords: Antimicrobial, Wound, healing, Dialium guineense, Cicatrin®, Phytochemical
  • Rahim Golmohammadi, Fatemeh Sabaghzadeh, Mohammad Shafi Mojadadi* Pages 227-232
    Anethum graveolens or Dill (local name: Shevid) belongs to the family of Apiaceae (Umbelliferae) and is used traditionally for the treatment of convulsion and diabetes in Iran. This study aimed to investigate the effect of hydroalcoholic extract of A. graveolens leaves on the histology of the dentate gyrus of thehippocampus in the epileptic mice kindled by Pentylenetetrazole (PTZ). In this experimentalstudy, the epileptic BALB/c mice kindled by PTZ were randomly divided into four groups of 10 animals each. Three experimental groups received 250, 500 and 750 mg/kg/day of A. graveolens extract for 21 days. The control group received phosphate-buffered saline (PBS). After the treatment period, the mice were anesthetized, and their hippocampi were dissected for the histopathological analysis, and immunohistochemical analysis for caspase-3 activity. Histopathological examinations showed that the mean numbers of the healthy neuronal cells in the dentate gyrus of the mice received 500 mg/kg/day of A. graveolens extracts were significantly higher than those of the mice received 250 and 750 mg/kg/day of the extracts as well as the control group (P
    Keywords: Anethum graveolens, Dentate gyrus, Hippocampus, Epilepsy
  • Ehsan Nabovati, Hasan Vakili, Arki, Zhila Taherzadeh, Mohammad Reza Saberi, Ameen Abu, Hanna, Saeid Eslami* Pages 233-242
    The objective of this study was to determine incidence rate, type, and pattern of clinically relevant potential drug-drug interactions (pDDIs) in a large outpatient population of a developing country. A retrospective, descriptive cross-sectional study was conducted on outpatients’ prescriptions in Khorasan Razavi province, Iran, over 12 months. A list of 25 clinically relevant DDIs, which are likely to occur in the outpatient setting, was used as the reference. Most frequent clinically relevant pDDIs, most common drugs contributing to the pDDIs, and the pattern of pDDIs for each medical specialty were determined. Descriptive statistics were used to report the results. In total, out of 8,169,142 prescriptions, 6,096 clinically relevant pDDIs were identified. The most common identified pDDIs were theophyllines-quinolones, warfarin nonsteroidal antiinflammatory drugs, benzodiazepines-azole antifungal agents, and anticoagulants-thyroid hormones. The most common drugs contributing to the identified pDDIs were ciprofloxacin, theophylline, warfarin, aminophylline, alprazolam, levothyroxine, and selegiline. While the incidence rate of clinically relevant pDDIs in prescriptions of general practitioners, internists, and cardiologists was the highest, the average pDDI incidence per 10,000 prescriptions of pulmonologists, infectious disease specialists, and cardiologists was highest. Although a small proportion of the analyzed prescriptions contained drug pairs with potential for clinically relevant DDIs, a significant number of outpatients have been exposed to the adverse effects associated with these interactions. It is recommended that in addition to training physicians and pharmacists, other effective interventions such as computerized alerting systems and electronic prescribing systems be designed and implemented.
    Keywords: Drug, drug interactions, Drug utilization review, Patient safety, Developing countries
  • Negin Mehdinezhad, Alireza Ghannadi, Afsaneh Yegdaneh* Pages 243-249
    Sea algae are widely consumed in the world. There are several seaweeds including brown algae which are authorized for human consumption. These plants contain important phytochemical constituents and have various potential biological activities. The present study investigated the presence of phytochemical constituents and total phenolic quantity of the seaweeds Sargassum angustifolium, Sargassum oligocystum and Sargassum boveanum. Cytotoxicity of seaweeds was tested against HT-29, HeLa and MCF-7 cell lines. Antioxidant potential of these 3 Sargassum species was also analyzed. Cytotoxicity was characterized by IC50 of human cancer cell lines using sulforhodamine assay. Antioxidant activities were evaluated using 2,2- diphenyl-1- picrylhydrazil. The analysis revealed that tannins, saponins, sterols and triterpenes were the most abundant compounds in these Sargassum species while cyanogenic and cardiac glycosides were the least ones. Sargassum angustifolium had the highest content of total phenolics (0.061 mg/g) and showed the highest antioxidant activity (IC50 = 0.231). Cytotoxic results showed that all species could inhibit cell growth effectively, especially MCF-7 cell line (IC50 = 67.3, 56.9, 60.4 for S. oligocystum, S. angustifolium and S. boveanum respectively). Considerable phytochemicals and moderate cytotoxic activity of S. angustifolium, S. oligocystum and S. boveanum make them appropriate candidate for further studies and identification of their bioactive principles.
    Keywords: Antioxidant, Cytotoxic, Sargassun angustifolium, Sargassum oligocystum, Sargassum boveanum, Seaweed
  • Hamzeh Rahimi, Ali Najafi *, Habib Eslami, Babak Negahdari, Mehrdad Moosazadeh Moghaddam Pages 250-258
    Owing to essential role in bacterial survival, DNA gyrase has been exploited as a validated drug target. However, rapidly emerging resistance to gyrase-targeted drugs such as widely utilized fluoroquinolones reveals the necessity to develop novel compounds with new mechanism of actions against this enzyme. Here, an attempt has been made to identify new drug-like molecules for Shigella flexneri DNA gyrase inhibition through in silico approaches. The structural similarity search was carried out using the natural product simocyclinone D8, a unique gyrase inhibitor, to virtually screen ZINC database. A total of 11830 retrieved hits were further screened for selection of high-affinity compounds by implementing molecular docking followed by investigation of druggability according to Lipinski's rule, biological activity and physiochemical properties. Among the hits initially identified, three molecules were then confirmed to have reasonable gyrase-binding affinity and to follow Lipinski's rule. Based on these in silico findings, three compounds with different chemical structures from previously identified gyrase inhibitors were proposed as potential candidates for the treatment of fluoroquinolone-resistant strains and deserve further investigations.
    Keywords: DNA gyrase inhibitor, Structural similarity, Molecular docking, Shigella flexneri, Simocyclinone D8
  • Filipp Filippovich Vasilyev, Diana Aleksandrovna Danilova, Vladimir Sergeevich Kaimonov, Yana Valerievna Chertovskih, Nadezda Romanovna Maksimova Pages 259-264
    Allele frequencies of single nucleotide polymorphisms (SNPs) are variable among different populations; therefore the study of SNPs in ethnic groups is important for establishing the clinical significance of the screening of these polymorphisms. The main goal of the research is to study the polymorphisms of CYP2C9, CYP2C19, VKORC1, and SLCO1B1 in Yakuts. Genomic DNA from 229 Yakut subjects were analyzed by real-time polymerase chain reaction (PCR) (SLCO1B1  > C, VKORC1 -1639G>A, CYP2C19 >A, >A, CYP2C9 С>T, 흎>C). Genotype frequencies of polymorphisms in the population of the Yakuts were more characteristic of the Asian population. The results have been included in the software application “Lekgen” that we developed for the interpretation of pharmacogenetic testing. The data of our study obtained on frequency carriers of polymorphisms of genes SLCO1B1, СYP2C19, CYP2C9, VKORC1 among the Yakuts may be useful in developing recommendations for a personalized therapy.
    Keywords: Polymorphism, Genotyping, Pharmacogenetics, Yakuts