فهرست مطالب

Pharmaceutical Sciences
Volume:26 Issue: 1, Mar 2020

  • تاریخ انتشار: 1399/01/07
  • تعداد عناوین: 14
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  • Jeena John_Naveen Kumar Sapa_Rekha R Shenoy Pages 1-12
    Background

    Virgin coconut oil (VCO) has been identified as a potential cognitive strengthener associated with Alzheimer’s disease (AD). It contains medium chain fatty acids (MCFA) which are absorbed and easily metabolized by the liver to form ketone bodies. Ketone bodies are converted to acetyl Co-A in the brain which then enters the citric acid cycle to provide ATP and also serves as precursors of acetylcholine in neurons. Sunflower oil (SO) contains poly unsaturated fatty acids which has both anti-inflammatory and neuroprotective actions. To compare the neuroprotective effects of VCO and SO on biochemical parameters involved in the cognitive dysfunction induced by colchicine through intracerebroventricular (i.c.v) route. To assess the role of polyphenols and MCFA present in VCO in preventing oxidative stress and its influence on in neuroprotection and memory enhancement.

    Methods

    In the present study, we induced dementia through i.c.v injection of colchicine after giving the diet enriched VCO and SO in rats for 60 days. Rats were sacrificed on the 22nd day after the administration of colchicine. Behavioral parameters were assessed during the study period and biochemical estimations were performed using frontal cortex and hippocampus isolated from rat brain.

    Results

    From the memory and learning tests by Morris water maze, VCO treated group performed better than SO treated rats. VCO reversed the antagonistic effects induced by colchicine by decreasing the acetylcholinesterase and malondialdehyde levels and increasing the levels of catalase and superoxide dismutase. SO only reduced malondialdehyde levels in cortex and hippocampus.

    Conclusion

    The results demonstrated potential beneficiary effects of VCO in the cognitive dysfunction induced by colchicine by enhancing acetylcholine levels in the frontal cortex and hippocampus and also by reducing oxidative stress induced by physiological oxidants.

    Keywords: Colchicine, Dementia-Diet, Sunflower oil, Virgin coconut oil
  • Seba Hassan*, Ali Abdelrahman Moustafa, Soad Lotfy Kabil, Nevertyty Mohamed Mahmoud Pages 13-24
    Background

    Metabolic syndrome (MS) is characterized by sustained hyperglycemia that triggers advanced glycation end products (AGEs) generation. Alagebrium (ALA) is an advanced glycation end products (AGEs) cross-links breaker.

    Methods

    32 Wistar rats were divided into normal control (NC) group (8 rats) and MS groups (24 rats) received a high carbohydrate high fat diet (HCFD) for 10 weeks. Rats with established MS were equally divided into 3 subgroups remained on HCFD for further 6 weeks: MS control (MSC), ALA treated received 10 mg/kg/day ALA orally and metformin treated (MF) (a reference drug) received 50 mg/kg/day MF orally. The studied parameters were systolic blood pressure (SBP), body and liver weights (BW, LW), LW/BW% ratio, fasting blood glucose (FBG), serum insulin, lipid profile, liver enzymes, serum AGEs, hepatic Interleukin-17 (IL-17), adipokines, pAkt/Akt ratio, and liver histopathology.

    Results

    HCFD elevated SBP, BW, LW and LW/BW% ratio, FBG, serum insulin, and AGEs. It also deteriorated lipid profile and liver enzymes, induced inflammation, insulin resistance and histopathological derangements. ALA ameliorated the elevated SBP, FBG, lipid profile, liver enzymes, mitigated insulin resistance, hepatic IL-17, serum AGEs, modulated adipokines levels and improved liver histopathology. However, MF had better effects than ALA in all studied parameters except AGEs.

    Conclusion

    ALA is protective against dietary-induced MS via ameliorating the inflammatory process and serum AGEs that implicated in MS pathogenesis, which makes it a promising new tool in MS treatment.

    Keywords: Advanced Glycation EndProducts, Alagebrium, Metabolic Syndrome, Metformin
  • Ajand Aboutalebi, Abolghasem Jouyban, Hadi Chavoshi, Aliakbar Movassaghpour Akbari, Elnaz Shaseb, Parvin Sarbakhsh, Saba Ghaffary* Pages 25-31
    Background

    Beta-thalassemia major patients require repeated blood transfusion which is associated with iron overload in different organs such as heart, liver, kidney and their related complications. In this study the effects of selenium in iron overload related complications of patients with beta-thalassemia major were assessed.

    Methods

    In this clinical trial, 34 beta-thalassemia major patients over 12 years old were enrolled. Patients with severe renal failure, history of selenium consumption over the last three months, change of blood transfusion pattern, and any change of chelating agent were excluded from the study. For all patients, tablet of selenium 200 µg/day was administered for a month. Blood samples were taken at baseline and after one-month to assess the level of ferritin, total iron-binding capacity (TIBC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (Scr), selenium. Hair loss was assessed by questionnaire before and after intervention.

    Results

    From 34 patients, 27 (79.4%) had deficient level of selenium at baseline. The selenium level was increased after intervention (p=0.005). The level of serum ALT and Scr decreased remarkably after one-month selenium consumption (p=0.007 for both). In addition, the AST level decreased remarkably after intervention (p=0.053). Severe hair loss profile has improved significantly after supplementation (p=0.004).

    Conclusion

    One-month selenium consumption improved liver and kidney function related markers remarkably. Moreover, selenium improved hair profile and severe hair loss in thalassemia patients. Further studies are needed on the effect of selenium administration on liver and kidney function.

    Keywords: Beta-thalassemia major, Selenium, Iron overload, Liver-Creatinine, Hair
  • Iraj Shahramian, Ali Bazi, Rosa Mostafaee, MohammadHasan Mohammadi* Pages 32-37
    Background

    There are controversies regarding the protective role of ursodeoxycholic acid (UDCA) against valproic acid (VPA)-induced hepatotoxicity in children. In the present clinical trial, we assessed the potential role of UDCA in preventing VPA-induced fluctuations of hepatic enzymes in epileptic children with recurrent seizures.

    Methods

    Two-hundred children with epileptic seizures were randomly allocated into either intervention (VPA+UDCA) or control (VPA+ placebo) group. Fluctuations of liver enzymes were recorded at baseline, as well as 48 hours, 1 month, and 3 months following the interventions.

    Results

    The mean age of the patients was 7.33±2.96 years (the range of 4-16). Males and females constituted 43 (43%) and 57 (57%) subjects in each group respectively. There were no significant differences in the baseline levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) between the intervention and control groups. At 48 hours postintervention, AST and ALT increased 1.7% and 11.05% (23.18±7.91 and 30.75±4.20 IU/l) in the intervention group and 21.3% and 35% (28.46±3.71 and 35.62±7.72 IU/l) in the control group respectively (P<0.0001). Both AST (P<0.001) and ALT (P=0.03) levels were significantly lower in the intervention than placebo group at 1-month post-intervention. At 3-month postintervention; however, while AST level still was significantly higher in the control (29.87±5.41 IU/l) than intervention (21.63±6.87 IU/l, P<0.0001), ALT level was not significantly different between the two groups (32.72±5.59 IU/l and 32.01±7.89 IU/l respectively, P=0.5).

    Conclusion

    UDCA can be an effective drug to manage VPA-induced fluctuations of hepatic enzymes in children with recurrent epileptic seizures.

    Keywords: Ursodeoxycholic acid, Valproic acid, Liver enzymes, Hepatic toxicity
  • Parisa Kiminejad Malaie, Mehdi Asadi, Faezeh Sadat Hosseini, Mahmood Biglar, Massoud Amanlou* Pages 38-44
    Background

    These days epilepsy is a common neurological disorder, which can affect on quality of life by unpredictable seizure. Thalidomide is one of the drugs to control the epilepsy but side effects such as teratogenicity, made it difficult to use.

    Methods

    Six new analogues of N-aryl-4-(1,3-dioxoisoindolin-2-yl)benzamides were synthesized and tested for anti-seizure activity. To evaluate the anti-seizure activity of these new derivatives, 40 mice in 8 groups were received 10 mg/Kg of each new derivatives 30 min before the injection of pentylenetetrazole (PTZ, 70 mg/kg) to induced seizures. Latency time to first symptom of seizure was measured and compared to vehicle and standard groups. Docking methodology was applied to study on mode of interaction between GABAA receptor and synthetized compounds.

    Results

    Structures of the all synthesized compounds were confirmed by NMR and mass spectroscopy. The latency time and mortality rate were individually measured for an hour after injection of pentylenetetrazole. Docking study revealed that synthesized compounds and thalidomide interact in similar conformation with GABAA receptor.

    Conclusion

    The experimental and docking results were found in good correlation and demonstrated that the most active compound (5a), with 3,4-dimethylphenyl residue increased the duration of seizure inhibition threshold in comparison with thalidomide

    Keywords: -Epilepsy, Molecular docking simulation, Phthalimide, Seizures, Thalidomide
  • Maryam HamzehMivehroud, Ayda BaghalSafarizad, Siavoush Dastmalchi* Pages 45-51
    Background

    Uncontrolled activity of tumor necrosis factor alpha (TNF-α) as pro-inflammatory cytokine has been linked with pathogenesis of autoimmune/inflammatory diseases. Therefore, modulating of TNF-α associated biological pathways is a promising strategy for alleviating of such diseases. In view of this, the use of antibody fragments such as single-chain variable fragments (scFv) in therapeutic applications has been gained much attention in terms of pharmacokinetic as well as production and therapeutic costs.

    Methods

    In the current investigation, the previously designed and humanized hD2 antibody was modeled and docked onto the TNF-α structure. The binding free energy was predicted for the complex of hD2-TNF-α using molecular dynamics calculation followed by per-residue energy decomposition for residues of hD2. In addition in silico mutations of important amino acids at the binding site of enzyme were performed and the binding free energy was calculated for mutant forms of scFv in complex with TNF-α.

    Results

    The analyses of the results proposed Y27F mutation in heavy chain CDR1 of hD2 scFv antibody may be considered as a promising substitution.

    Conclusion

    The results may be used for designing new anti-TNF-α antibody with improved activity

    Keywords: Binding free energy, hD2 scFv antibody, Molecular dynamics simulation, Molecular modeling-TNF-α
  • Ali Mohebbi, Saeid Yaripour*, MirAli Farajzadeh, MohammadReza AfsharMogaddam, Hassan Malekinejad Pages 52-60
    Background

    In the present work, a miniaturized sample preparation method based on combination of dispersive solid phase extraction and temperature–induced homogenous liquid– liquid microextraction has been proposed for the extraction and preconcentration of some organophosphorus pesticides (parathion–methyl, triazophos, parathion, diazinon, and phoxim) from honey samples prior to their analysis by high performance liquid chromatography– ultraviolet detection.

    Methods

    In this method, initially the analytes were adsorbed onto a sorbent (C18) and then desorbed by the use of cyclohexyl amine as an eluent. In the next step, the eluent was mixed with water thermostated at 0 °C to obtain a homogenous solution. By increasing the temperature, the solubility of cyclohexyl amine in water was decreased and led to formation of dispersed fine droplets in the whole of solution. These droplets go up through the solution and collected on top of the solution. Finally, an aliquot of the organic phase was sucked in a microsyringe and injected into the separation system for analysis.

    Results

    Under the optimum experimental conditions, limits of detection and quantification were calculated to be in the ranges of 0.90–1.75 and 3.0–5.8 ng g–1 in honey samples, respectively. Enrichment factors and extraction recoveries were in the ranges of 148–183 and 59–73%, respectively. The relative standard deviations varied from 2–4% and 4–5% for intra– (n = 6) and inter–day (n = 4) precisions, respectively.

    Conclusion

    The suggested approach was satisfactorily utilized to the analysis of 21 honey samples. The proposed miniaturized tandem sample pretreatment method enhanced the sensitivity of the instrumental analysis.

    Keywords: -Solid phase extraction, Liquid–liquid microextraction, Honey, Organophosphorus pesticide
  • Maryam Maghsoodi, Seyedhassan Montazam, Hossein Rezvantalab, Mitra Jelvehgari* Pages 61-74
    Background

    Atorvastatin (AT), as a synthetic lipid-lowering agent, is a highly crystalline substance having poor solubility and low bioavailability. The objective of the present research was to improve the microprecipitation method of AT suspension preparation.

    Methods

    Microprecipitation parameters were improved using Box-Behnken experimental design method. The suspension was formulated with Brij 35 (stabilizer agent) using methanol as solvent and water as non-solvent, respectively. DSC, XRD, FTIR studies were performed for characterization of the microcrystals. With the aim of evaluating the effect of independent variables, the amounts of organic solvent (X1), emulsifier concentration (X2), stirring rate (X3), and volume of aqueous solvent (X4) on dependent variables, drug content (DC,) particle size (PS), drug released after 5 minutes (Q5), Gibbs free energy change (ΔG°tr), crystal yield (CY) and saturated solubility (Ss), a full factorial was used.

    Results

    The results of DSC, XRD, and FTIR showed that there was not any interaction between AT and Brij 35. This research demonstrated a reduction in crystallinity in agglomerates. The microcrystals showed that micromeritics characteristics were significantly improved compared to pure AT. The content of drug and yield crystal was in the limit of 42.58-110.24% and 58.33- 98.18% in all formulations, respectively. It was shown that the prepared microcrystals had a higher rate of release compared to the untreated AT powder (P< 0.05). Size reduction of AT is needed for improving the solubility. Solubility and drug release rates of At was enhanced with the microprecipitation method.

    Conclusion

    The results showed that microcrystals significantly increased AT dissolution rate.

    Keywords: Atorvastatin, Suspension, Microprecipitation, Box-Behnken Method, Brij 35, Microcrystal
  • Kadali Jagadeesh, Nowduri Annapurna* Pages 75-81
    Background

    The combination of chlorthalidone and benidipine was used to manage hypertension. The mixture of chlorthalidone and benidipine in tablet dosage form has not been previously determined by any method. A stability indicating HPLC method was developed for the simultaneous determination of benidipine and chlorthalidone in bulk and tablets.

    Methods

    Chromatographic separation was accomplished in a reverse phase system using an isocratic elution with a mobile phase composed of methanol-0.1M dipotassium hydrogen phosphate buffer (40:60, v/v), at 1 ml/min flow rate. The photodiode array (PDA) detector set at 260 nm was used to detect and quantify benidipine and chlorthalidone. Benidipine and chlorthalidone tablet samples were subjected to degradation under acid, neutral, alkali, thermal, photo and oxidative. The proposed method was effectively adapted to quantify benidipine and chlorthalidone in the combined tablet formulation.

    Results

    The elution times for benidipine and chlorthalidone were approximately 4.573 min and 6.422 min, respectively. The method was validated within a concentration range of 2 - 6 μg/ml (R2 = 0.9997) for benidipine and 6.25 - 18.75 μg/ml (R2 = 0.9998) for chlorthalidone. Adequate results were obtained for precision (RSD% = 0.106% for benidipine and RSD% = 0.031% for chlorthalidone) and accuracy (99.95 - 100.25 % mean recovery for benidipine and 99.60 - 99.63% mean recovery for chlorthalidone). Robustness has also been found to be acceptable. During the degradation study, interference was not noticed in the analysis of studied drugs.

    Conclusion

    The findings demonstrated that the method could be useful for determination of the selected drug combination in routine analysis.

    Keywords: Benidipine, Chlorthalidone, Degradation, Tablets, HPLC-Analysis
  • Peter Adukwu Odekina, Matthias Onyebuchi Agbo*, Edwin Ogochukwu Omeje Pages 82-87
    Background

    Bacillus species represent a rich source of new bioactive metabolites that can combat diseases.

    Methods

    Bacillus strain was isolated from the marine sponge Spongia officinalis and routinely maintained on marine broth. The bacteria strain was identified as Bacillus 2011SOCCUF3 using 16S rDNA sequencing. The strain was cultured on Tryptone Casein Oat Soluble Starch (TCOATSS) media with continuous agitation for 4 days. The fermented broth was centrifuged, and the supernatant was mixed with 10% (w/v) of adsorbent resin (XAD-7HP and XAD-16N, 1:1) and shaken continuously at a reduced speed for 7 h; and the resin was collected by filtration through sintered glass funnel and washed with MilliQ water, and then eluted with methanol to obtain the extract. The extract was evaporated in vacuo at reduced temperature and pressure to obtain the dry extract. The dry extract was purified by vacuum liquid chromatography, eluting with methanol in acetone gradient. The in vitro antimicrobial and antioxidant activities were investigated using the agar-well diffusion, DPPH scavenging and the phosphomolybdate methods respectively.

    Results

    The extract and fractions showed good antimicrobial activities with minimum inhibitory concentration range of <1.0 mg/mL. The extract and fractions also exhibited good antioxidant activities with their IC50 values been comparable to the standard.

    Conclusion

    Thus, a novel Bacillus strain isolated from the marine sponge (Spongia officinalis) obtained from Cortiou and Riou, France, exhibited promising antimicrobial and antioxidant activities.

    Keywords: Bacillus 2011SOCCUF3, Antimicrobial activity, Antioxidant activity, Spongia officinalis-TCOASS, Fermentation
  • Vahideh Tarhriz, Shirin Eyvazi, Elia Shakeri, MohammadSaeid Hejazi, Azita Dilmaghani* Pages 88-92
    Background

    Recently, resistant pathogenic microorganisms have become increasingly wide spread. The search for new natural antibiotics is a viable solution to this problem. For this aim we investigated the antimicrobial ability of Tabrizicola aquatica, the novel bacterium isolated from Qurugol Lake located nearby Tabriz city, Iran.

    Methods

    The antimicrobial properties of Tabrizacola aquatica was investigated using well diffusion test. Tabtizicola aquatica was incubated at 40℃ in shaking incubator at 150 rpm for 14 days. The culture was centrifuged to obtain cell free supernatant, which was sterilized using 0.2 μm filter paper and lyophilized. Microorganisms were lawn and then wells were prepared over the agar plates. About 100 ml of the diluted lyophilized supernatant was added to the wells. The plates then were incubated at 37℃. After 48 hours, antimicrobial activity was defined by measuring the inhibition zone diameter.

    Results

    The bacterial filtrates had considerable antagonistic effect against Escherichia coli, Rhizobium radiobacter, Pseudomonas syringae, Erwinia amylovora, Botrytis cinerea, Neurospora crassa and Fusarium oxysporum. However, the filtrates did not show any inhibitory action on the Aspergillus flavus and Klebsiella pneumonia. The supernatant decreased the growth zone on Streptococcus aureus, Pseudomonas aeruginosa, Shigella flexneri, Xanthomonas camoestris and Bassilus cereos. The result of MIC against pathogens was found for Neurospora crassa in the 50 µg/mL.

    Conclusion

    The results, suggested that Tabrizicola aquatica and similar bacteria can be helpful to control freshwater natural water sources from pathogenic microorganism. Moreover, microbial natural products are still the most promising source of new antibiotics. Our results point out a scope for characterization of the metabolites and could be a candidate in the identification of novel antibiotics.

    Keywords: Tabrizicola aquatica, Freshwater bacterium, Antibacterial Antifungal, Activity
  • Ali Shayanfar, Sanaz Hamedyazdan, Alireza Garjani* Pages 97-98