فهرست مطالب

Pharmaceutical Sciences - Volume:24 Issue: 1, Mar 2018

Pharmaceutical Sciences
Volume:24 Issue: 1, Mar 2018

  • تاریخ انتشار: 1397/01/28
  • تعداد عناوین: 12
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  • Sibel A. Ozkan* Pages 1-2
  • Afaf Al Groshi, Andrew R. Evans, Fyaz Ismail, Lutfun Nahar, Satyajit D. Sarker* Pages 3-7
    Background
    The current study was undertaken to assess the cytotoxicity of the leaves of Libyan Juniperus phoenicea (Cupressaceae) against human cancer cell lines.
    Methods
    The cytotoxicity of the n-hexane, dichloromethane (DCM) and methanol (MeOH) extracts of the leaves of J. phoenicea (JP), obtained from sequential Soxhlet extractions, was assessed against four human cancer cell lines: EJ138 (human bladder carcinoma), HepG2 (human liver hepatocellular carcinoma), A549 (human lung carcinoma) and MCF7 (human breast adenocarcinoma) using the MTT assay.
    Results
    The cell line A549 was the most sensitive to the JP extracts, with the highest level of cytotoxicity with the IC50 values of 16, 13 and 100 µg/mL for the DCM, n-hexane and MeOH extracts, respectively. However, generally the most potent cytotoxic extract across the other cells tested was the n-hexane extract, followed by the DCM extract, whilst the MeOH extracts showed little or no cytotoxicity. The percentage of viability of cells decreased as the concentration of test compounds increased. The cytotoxicity of various chromatographic fractions from the extracts was also studied against the A459 cells. For the n-hexane fractions, the IC50 values were 160, 62, 90, 30, 9.5 and 40 µg/mL for fractions 1 to 5 and 7, respectively. Fractions 4 and 5 showed the greatest effect. DCM fractions 2, 3 and 4 had the IC50 values of 60, 92 and 19 µg/mL, respectively, and DCM fractions 5 to 8 were non-cytotoxic. Fractions 1 and 2 of the MeOH extract were non-cytotoxic, whereas cytotoxicity was observed for fractions 3 and 4 with IC50 values of 50 and 85 µg/mL, respectively.
    Conclusion
    The outcome of the present study suggested that the JP leaves possess cytotoxic activities. The high level of cytotoxicity of the n-hexane and DCM extracts suggested that lipophilicity might affect the cytotoxicity of JP, where the less polar compounds had the strongest cytotoxicity.
    Keywords: Juniperus phoenicea, Cupressaceae, Cytotoxicity, Cancer cell lines, Solid phase extraction, Vacuum liquid chromatography
  • Haleh Vaez, Alireza Garjani, Abbas Delazar, Maryam Rameshrad, Negisa Seyed Toutounchi, Elhameh Nikkhah, Parina Asgharian* Pages 8-14
    Background
    Coronary artery disease is a leading cause of death worldwide. The present study has been designed to investigate efficacy of methanolic extract of Scrophularia subuphylla (S. subuphylla) on ischemia and reperfusion-induced myocardial injury in isolated rat heart.
    Methods
    The isolated male Wistar rat hearts (n= 5) were perfused by Krebs-Henseleit solution enriched with the extract (0, 1, 5, and 10 μg/ml), using the langendorff method. After 15 minutes stabilization, the hearts were subjected to 30 minutes regional ischemia and then 120 minutes reperfusion.
    Results
    Administration of the extract did not improve any of cardiac markers of flow rate, heart rate and developed pressure. Number, percentage and duration of arrhythmias were not affected by any concentrations of the extract. However, the concentration of 1 and 5 µg/ml increased the VT duration compared to control group (P
    Conclusion
    Generally, the methanolic extract of S. subuphylla at the doses which studied exhibited no protective effects against I/R-induced injures, which might be due to the high amount of cardiac glycosides with low therapeutic index.
    Keywords: Scrophularia subuphylla, Ischemia, Reperfusion, Arrhythmia, Infarct size, Isolated heart
  • Leila Hosseinzadeh, Shima Soheili, Nastaran Ghiasvand, Farahnaz Ahmadi, Yalda Shokoohinia* Pages 15-22
    Background
    Fatty acids (FAs), the key structural elements of dietary lipids, are notable in the nutritional value of plants. Black cumin, a popular anti-inflammatory and antioxidant food seasoning, contains nonpolar constituents such as FAs.
    Methods
    Seeds were extracted using hexane and their cytoprotective activity was assessed against doxorubicin (DOX)-mediated oxidative stress and apoptosis in PC12 cell line.
    Results
    In spite of the cellular death induced by DOX toward PC12 cells, bioassay-guided purification showed that pretreatment with FAs mixtures (24h) attenuated DOX-mediated apoptosis, which could be attributed to the inhibited caspase 3 activity and enhanced mitochondrial membrane potential. Palmitic acid, caprylic acid and oleic acid each 1/3 in the mixture, also suppressed DOX-induced ROS generation.
    Conclusion
    Our observation indicated that the subtoxic concentration of FAs from Nigella sativa could effectively protect the cells against oxidative stress, due to their antioxidant activity, and could be regarded as a dietary supplement.
    Keywords: Palmitic acid, Oleic acid, Stearic acid, Linoleic acid, Caprylic acid, Pheochromocytoma Cells
  • Mohammadmehdi Hassanzadeh-Taheri, Mehran Hosseini, Mojtaba Salimi, Hesam Moodi, Davood Dorranpour* Pages 23-30
    Background
    Oral consumption of Astragalus hamosus L. (AH) seedpod has been widely prescribed in traditional medicine system. However, its toxicity evaluation has never been investigated. Hence, the current study was performed to evaluate the toxicological profile of AH seedpod in acute and subacute assessments based on the OECD-guidelines 425 and 407 in male and female Wistar rats.
    Methods
    In the acute study, ethanolic extract of AH at a single dose of 2000 mg/kg was orally administrated to six female rats. In the subacute assay, AH at the three different oral doses (75, 150 and 300 mg/kg) were administrated to both male and female rats for 28 consecutive days.
    Results
    No death or behavioural changes were observed in the treated animals. In subacute test, in both sexes, no changes in organ weights observed. Biochemically, compared to the control, AH at the dose of 300 mg/kg slightly increased (p
    Conclusion
    It could be concluded that high excessive and long term consumption of AH may lead to renal dysfunction and deficiency in hematopoietic system.
    Keywords: Astragalus hamosus, Ethanolic extract, Acute toxicity study, Subacute toxicity study, Rat
  • Niusha Sharifi, Khosro Khajeh, Shabnam Mahernia, Saeed Balalaie, Ghasem Ataie, Raheleh Jahanbani, Massoud Amanlou* Pages 31-37
    Background
    Somatic ACE is a two-domain protein, C and N which are resulted from gene duplication. Presence of two active sites with particular properties, demonstrates functional significance of each domain. Increased levels of circulating N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), could be the result of ACE N-domain selective inhibition. Moreover, ACE C-domain specific inhibitors are able to inactivate bradykinin and inhibit the conversion of angiotensin I to angiotensin II in order to regulate blood pressure as well as reduced side effect profiles.
    Methods
    The present study was designed to determine ACE domain specificity of the novel ACE inhibitor, onopordia which was recently isolated from Onopordon acanthium L. The ACE inhibition activity was determined using Abz-SDK (Dnp)P-OH and Abz-LFK(Dnp)-OH as ACE domain selective substrates. IC50 values of onopordia determined and compared with those of captopril as the standard.
    Results
    IC50 values of onopordia for ACE N and C- domains were 180 µM and 244 µM respectively which demonstrated approximately similar affinity of the mentioned compound to ACE C and N-domains. A pharmacophore model was further generated based on onopordia interactions with the relevant ACE domain active sites.
    Conclusion
    According to onopordia interactions in the ACE C and N-domain active sits, it is a potential to generate more potent and also specific inhibitor based on this new scaffold by doing accurate adjustments. Therefore, this study provides the molecular basis for further designing ACE inhibitors, which are new therapeutics in combating tissue fibrosis diseases.
    Keywords: Angiotensin-I converting enzyme, ACE N-domain, ACE C-domain, Onopordon acanthium L., AcSDKP, Fibrosis
  • Farideh Vaziri*, Zahra Sahebkarm, Reza Bahrami, Saeedeh Pourahmad, Sara Azima Pages 38-43
    Background
    Excessive crying is a self-limiting problem and disappears in a few weeks, however, it can be irritating for the parents, leading to maternal depression or exhaustion, and stress in the parents. The study evaluated the effect of lavender oil inhalation on duration of daily crying in the infants who suffered infantile colic.
    Methods
    In this double blind randomized clinical trial, the main inclusion criteria were: healthy infants, no consumption of any drugs for infantile colic, healthy mothers, having one crying episode ≥ 2 hours per day (prolonged crying).
    The intervention group received inhalation of lavender oil and the control group received sweet almond oil for seven days. Duration of crying in the four parts of a day (morning, afternoon, evening, and night) was gathered by phone call. Also, maternal mood score was assessed at baseline and 7th day of intervention by the Edinburgh Postnatal Depression scale.
    Results
    At baseline, the two groups were not different in relation to infant’s crying duration. However, they were significantly different after intervention in all seven days of the study (p
    Conclusion
    The results suggest that a 1% concentration of the lavender oil can alleviate the colic symptoms and results in maternal mood improvement.
    Keywords: Infantile colic, Aromatherapy, Lavender oil, Excessive crying
  • Elnaz Vaghef-Mehrabani, Aziz Homayouni-Rad, Beitullah Alipour, Leila Vaghef-Mehrabany, Maryam Saghafi-Asl* Pages 44-51
    Background
    Probiotics are live microorganisms with immune-regulatory properties and may be useful for patients suffering from rheumatoid arthritis (RA), an autoimmune inflammatory disorder. The aim of the present study was to formulate L. casei 01 capsules at laboratory scale, and evaluate its effects on the proportion of T-helper type 2 (Th2) anti-inflammatory cytokines to T-helper type 1 (Th1) pro-inflammatory cytokines (Th2/Th1), in RA patients.
    Methods
    After blending the probiotic and excipient (maltodextrin) based on the relevant calculations, the content uniformity of the mixture was evaluated. Furthermore, viability of the probiotic bacteria was assessed during capsules production and throughout three months of storage. In a randomized double-blind placebo-controlled trial, 46 RA patients were supplemented with either the capsules (containing at least 108 CFU of Lactobacillus. casei 01) or placebo (maltodextrin), for eight weeks; DAS28 (Disease activity score 28) as well as serum inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10 and IL-12) were measured at baseline and the end of study. IL-10/IL-1β, IL-10/IL-6, IL-10/IL-12, IL10/TNF-α and IL-10/(IL-1β IL-6 IL-12 TNF-α) were calculated, the latter being expressed as IL-10/total Th1, and compared for the groups. Paired samples t test, Wilcoxon signed-rank test and ANCOVA tests were applied.
    Results
    Probiotic powder had been uniformly mixed with the excipient and the bacteria had acceptable viability throughout the study course. Supplementation of RA patients with the capsules resulted in a significant decrease in disease activity (DAS28, P=0.039) and increase in IL-10/TNF-α, IL-10/IL-12 and IL-10/total Th1 (P=0.039, P=0.012 and P=0.014, respectively). At the end of the study, there was a significant difference between the two groups in terms of IL-10/IL-12 and IL-10/total Th1 (P= 0.038 and P= 0.006, respectively).
    Conclusion
    L. casei 01 supplements may have the expected desired anti-inflammatory effects in RA patients. Further clinical trials are warranted to confirm these results.
    Keywords: Cytokines, L. casei 01, Probiotic, Rheumatoid arthritis, Supplement, T-helper cells
  • Sajedeh Bahrani, Babak Ghanbarzadeh, Mahmoud Sowti Khiabani, Saeed Ghanbarzadeh, Hamed Hamishehkar* Pages 52-59
    Background
    The formation of electrostatic complexes between two types of biopolymers, sodium Caseinate (a derivative from most abundant milk protein) and Pectin (a natural hetro polysaccharide), was studied as a function of biopolymers concentrations and pH of solutions (3.9- 4.3).
    Method
    The size and morphology of the resulted complexes were investigated by using of laser light scattering and transmission electron microscopy, respectively. Response surface methodology (A three-factor, three levels Box-Behnken design) was used for the optimization procedure with pH, pectin and sodium Caseinate concentrations as independent variables. Particle size and polydispersity index of nanocomplexes were considered as dependent variables.
    Results
    Negatively charged nanocomplexes were produced below the isoelectric point of protein (5.4), at pH 4.1 with a suitable colloidal stability and average particle size of about 100 nm. It was found that the particle size of nanocomplexes could be controlled by changing in variables.
    Conclusion
    In conclusion response surface methodology are simple, rapid and beneficial approach for preparation, optimization and investigation of the effect of independent variables on the properties of products.
    Keywords: Pectin, Sodium Caseinate, Nanocomplex, Response Surface Methodology, Box-Behnken Design
  • Farnaz Monajjemzadeh, Mahsa Bagheri, Seyed Hassan Montazam, Mitra Jelvehgari* Pages 60-70
    Background
    Selegiline hydrochloride (Sel) is a drug applied for the therapy of early‐step Parkinson's disease. In usual clinical doses, it is an elective irreversible MAO-B inhibitor. This study intended to formulate mucoadhesive microspheres of selegiline with the objective of improving the therapeutic efficacy, patient compliance and bioavailability.
    Methods
    The microspheres were prepared by emulsion solvent evaporation method (O1/ O2) using hydroxypropyl methylcellulose (HPMC). In the current study, bucco‐adhesive microspheres were prepared with different drug to polymer ratios and characterized by encapsulation efficiency, particle size, Differential Scanning Calorimetry (DSC), FTIR Fourier Transform Infrared Spectroscopy (FTIR), flowability, the degree of swelling and surface pH, mucoadhesive character, retentive time, and drug release studies.
    Results
    The best drug to polymer ratio in microspheres was 1:2 (as F1). The production yield microspheres F1 showed production yield of 84.79%, mean particle size of 744.73 μm and loading efficiency of 53.33%. The DSC exhibited the property of selegiline loaded microspheres changed to amorphous form. The FTIR spectrum proposed that the drug kept its chemical stability during the emulsification process. The results showed that the microspheres of F1 had faster release than the microspheres of F2 (1:4), F3 (1:6), and commercial tablet (p
    Conclusion
    The formulations were found to be appropriate candidates for the improvement of microspheres for the remedial objects.
    Keywords: Muco‐adhesive, Microparticle, Hydroxypropylmethyl cellulose, Selegiline, Disc
  • Akbar Rezazadeh, Mohammad Amjadi, Jamshid L. Manzoori, Alireza Ghaffari, Abolghasem Jouyban* Pages 71-78
    Background
    A new, fast and sensitive spectrofluorimetric method was proposed for the determination of furosemide in serum samples based on a dispersive liquid-liquid microextraction.
    Methods
    The optimum conditions for quantification of furosemide were studied considering the effects of types and amounts of dispersive and extraction solvents, salt addition, pH value, rate and duration of centrifugation. The method was validated with respect to the linearity, recovery and limit of detection.
    Results
    Under the optimal conditions, the fluorescence intensities at 406 nm (with the excitation wavelength of 342 nm) were linear with the concentration of furosemide in the range of 0.3 to 20 µg mL-1, with a detection limit of 0.12 µg mL-1 and a relative standard deviation of 3.4–9.4%.
    Conclusion
    Careful examination of the obtained validation results reveal that the proposed method is suitable for determination of furosemide in serum samples.
    Keywords: Furosemide, Analysis, Pharmacokinetic, Doping, Spectrofluorimrtry, Serum
  • Ali Banagozar Mohammadi, Maryam Zaare Nahandi, Negin Raad, Siroos Javani, Afshin Gharekhani* Pages 79-82
    Background
    Organophosphorus (OP) poisonings, a common source of pesticide poisoning, are an important cause of morbidity and mortality in the developing countries. Combination therapy with atropine and oxime is a common practice in the management of OP poisoning. However, the additive benefit of using pralidoxime in addition to atropine remains controversial. Due to inappropriate and widespread use of this relatively expensive and low available antidote, we aimed to evaluate its usage in an Iranian teaching hospital.
    Methods
    Medical files of patients with pesticide poisoning who had been admitted to the poisoning ward between September 2013 and September 2014 were reviewed. Patients with definite diagnosis of OPs poisoning were selected to evaluate rational use of pralidoxime in their treatment regimen. Data were collected using a checklist containing demographic, clinical, and para clinical characteristics, as well as the type of pesticide poisoning. Appropriateness of the pralidoxime therapy was determined based on clinical practice guideline and endorsed by an attending medical toxicologist.
    Results
    68.8% of patients had been poisoned with insecticides, 27.1% with aluminum phosphide, 2.1% with herbicides, and 2% with rodenticides, respectively. OPs were responsible for 43.8% of all poisoning. All patients with OPs poisoning received pralidoxime after they had been admitted to emergency department, while only 55% of them were eligible to receive pralidoxime. Moreover, pralidoxime had been administered for 59% of patients with non-OPs poisoning, which all of them were clinically inappropriate.
    Conclusion
    The use of pralidoxime in the northwest of Iran is not appropriate and thus, it is highly recommended that a patient-tailored treatment guideline be provided and implemented regionally.
    Keywords: Antidote, Organophosphate, Poisoning, Pralidoxime