PHARMACEUTICAL SCIENCES
Year:2017 | Volume:23 | Issue:2|Papers Count:12

To see the future, we must look at the past (German proverb).A QSAR (quantitative structure-activity relationship) is a mathematical equation that relates a property of interest such as a biological potency with one or more molecular properties (called descriptors), for a series of (usually) related compounds...

The dawn of the state-of-the-art methods of drug/gene delivery, nano-based delivery systems for delivery of pharmaceutically active agents into the target sites in the body have been developed. Among these, a concerted effort has been directed towards the development of biodegradable/biocompatible nanomaterials with the high potential benefits of passive/active targeting and reduced undesirable side effects. Since polysaccharides offer a large number of available reactive groups, specific targeting could be obtained by the surface coating of nanoparticles with targeting ligands. On the other hand, mucoadhesive properties of polysaccharides can be used for prolonging the residence time of delivery systems at the site of absorption. This study reviews a number of important polysaccharides with a perspective on the challenges, advantages, and disadvantages of their applications as drug/gene delivery systems.

Background: Propylthiouracil (PTU) administration is associated with several cases of hepatotoxicity, especially in children. The mechanism (s) of PTU-induced hepatotoxicity is obscure. In the current study, we aimed to assess the effect of PTU on hepatocytes mitochondria in different experimental models.Methods: Mice were treated with PTU (10, 20, 40, 80, and 100 mg/kg, i.p) then, the liver mitochondria were isolated and evaluated. Moreover, liver mitochondria were isolated from normal mice and incubated with increasing concentrations of PTU (10 mM-1 mM). Mitochondrial dehydrogenases activity, mitochondrial membrane potential, mitochondrial swelling, and mitochondrial adenosine triphosphate (ATP) content were monitored.Results: PTU hepatotoxicity was biochemically evident in mice by increased serum biomarkers of liver injury. PTU also caused a decrease in mitochondrial dehydrogenases activity, increased mitochondrial swelling, depleted mitochondrial ATP, and caused mitochondrial depolarization both in vitro and in vivo.Conclusion: Our data suggest mitochondrial dysfunction as a mechanism for PTU-induced hepatotoxicity.

Background: Rosmarinic acid is a polyphenolic compound with considerable antioxidant activities. We aimed to investigate its cardioprotective effects against isoproterenol-induced myocardial infarction (MI) in rats.Methods: Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatments with 10, 20, 40 mg/kg of rosmarinic acid. Myocardial infarction was induced by subcutaneous injection of isoproterenol (100 mg/kg) once daily for 2 days. Rosmarinic acid was injected intraperitoneally once daily for 4 days, from the day of isoproterenol injection. In the fifth day the animals were anesthetized and hemodynamic and electrocardiographic parameters were recorded. After collecting the blood samples, the hearts were removed, weighed immediately to measure the cardiac enlargement, and kept for further histological studies. Lactate dehydrogenase and malondialdehyde were measured in the heart tissues for evaluating the damages and lipid peroxidation, respectively.Results: Rosmarinic acid revealed a considerable antioxidant activity in vitro, with IC50 of 6.43mg/ml. Isoproterenol induced cardiac arrhythmias, myocardial damage and cardiac enlargement. Rosmarinic acid significantly reduced peripheral neutrophil percentage and inhibited isoproterenol-induced ST-segment elevation and R-amplitude depression in the infarcted hearts. It also significantly increased the mean arterial pressure and heart rate and decreased the left ventricular end diastolic pressure. The ventricular contractility was considerably improved by rosmarinic acid. Histopathological evaluations showed that rosmarinic acid significantly diminished the post-MI necrosis and fibrosis in the myocardium and inhibited the cardiac edematous.Conclusion: It is deducible from the results that rosmarinic acid improves the cardiac performance and inhibits post-MI myocardial depression, probably due to its anti-oxidative activity.

Background: Colorectal cancer is a common cause of cancer-related deaths Epigenetic regulation of the influx sodium dependent monocarboxylate transporter-1) SMCT1), a tumor suppressor, was recognized in colorectal cancer. In this study, effects of Curcumin (Cur), on SMCT1 gene expression was determined. A low SMCT1 expression, HCT116, cell line was used to test an in vitro effect of Cur on epigenetic regulation of SMCT1 expression via DNA methylation and its function. It was hypothesized that Cur can induce SMCT1 expression in the cells via hypomethylation effect. Measurement of increase in SMCT1 function was performed using dichloroacetate (DCA), a cytotoxic substrate of SMCT1.Methods: The effect of 5′Azacytidine (Aza), a hypomethylating agent, and Cur on SMCT1 expression and function was determined. Cells were treated with Aza and various concentrations of Cur for 72 h. After that SMCT1 expression was determined by real time PCR and Western blotting. To evaluate the SMCT1 function, DCA was used in MTT assay.Results: After treatment with 40 mM Cur, SMCT1 mRNA was significantly increased (p<0.05). This was correlated with SMCT1 protein expression. Cells treated with 40 mM of Cur showed significant increase of cytotoxicity at DCA concentrations of 25 (p<0.001) and 12.5 mM (p<0.01), respectively.Conclusion: Cur was shown to significantly induce the SMCT1 mRNA and protein expression in HCT116 cells. The induction of the SMCT1 protein increased DCA cytotoxicity, presumably through an increase of DCA transport into the cells. The mechanism underlying of SMCT1 induction by Cur may result from not only hypomethylation but other epigenetics.

Background: Analysis of chemicals in biological fluids is required in many areas of medical sciences. Rapid, highly efficient, and reliable dispersive and air assisted liquid–liquid microextraction methods followed by gas chromatography-flame ionization detection were developed for the extraction, preconcentration, and determination of 2-octanone in human plasma and urine samples.Methods: Proteins of plasma samples are precipitated by adding methanol and urine sample is diluted with water prior to performing the microextraction procedure. Fine organic solvent droplets are formed by repeated suction and injection of the mixture of sample solution and extraction solvent into a test tube with a glass syringe. After extraction, phase separation is performed by centrifuging and the enriched analyte in the sedimented organic phase is determined by the separation system. The main factors influencing the extraction efficiency including extraction solvent type and volume, salt addition, pH, and extraction times are investigated.Results: Under the optimized conditions, the proposed method showed good precision (relative standard deviation less than 7%). Limit of detection and lower limit of quantification for 2-octanone were obtained in the range of 0.1-0.5 mg mL-1. The linear ranges were 0.5-500 and 0.5-200 mg mL-1 in plasma and urine, respectively (r2≥0.9995). Enrichment factors were in the range of 13-37. Good recoveries (55-86%) were obtained for the spiked samples.Conclusion: Preconcentration methods coupled with GC analysis were developed and could be used to monitor 2-octanone in biological samples.

Background: TiO2 nanoparticles (NPs) which are used in sunscreen formulations are able to block ultraviolet (UV) radiation with a higher efficiency compared with micro-scale particles. The concentration of corresponding particles is an important factor in UV attenuation effects as well as cell toxicity profiles. Herein, TiO2 NPs were dispersed using ultrasonication treatment and a sunscreen cream was prepared using TiO2 NPs.Methods: The effect of TiO2 concentration (i.e. a physical barrier) and octocrylene (i.e. a chemical UV filter) as well as sonication time (i.e. aggregation preventer) were studied on UVB blocking efficiency of the preparation by measurement of sun protection factor (SPF). Response surface methodology was employed to investigate the effect of the inputs (independent parameters) on the output (dependent parameter).Results: Findings indicated that maximum amount of nano-TiO2 and octocrylene make the preparation most effective. The effect of ultrasonication in breaking the agglomerates was however dominated by the effect of concentration of octocrylene, possibly due to hydrophobic interactions between NPs and octocrylene. Also, TiO2 NPs showed a significant increase in cytotoxicity profile of the preparation.Conclusion: In conclusion, introduction of the nanoparticles, as the dominant factor, to the sunscreen product increased both efficacy and cytotoxicity of the product.

Background: The objective of this study was to analyze the essential oil, fatty acid, flavonoid, phenolic compounds and in vitro antioxidant activity of oil from Feverfew (Tanacetum parthenium L.) wild grown and collected from north of Iran.Methods: The essential oil of aerial parts was analyzed by spectroscopy method (GC/MS using HP-5MS column) while the fatty acid content was analyzed by gas chromatography (GC/FID). Phenolic contents of the oil were evaluated using high performance liquid chromatography (HPLC/UV) technique while total phenols and flavonoids were determined colorimetrically. The in vitro antioxidant activity of the essential oil was evaluated by 1, 1-diphenyl-2 picryl hydrazyl (DPPH) radical scavenging technique.Results: In the essential oil thirteen compounds were characterized with camphor (43.97 %), chrysanthenyl acetate (12.46 %) and farnesol (7.54%) as the major components. Principal fatty acid components of the herb were palmitic acid (57.27%) and myristic acid (14.7%). HPLC analysis revealed that the cinnamic acid derivatives were the major compounds, with sinapic (3.86±0.1 mg/g dw) and ferulic (2.59±0.1 mg/g dw) acids being the predominant ones. Also, evaluation the bioactivity of the oil showed considerable antioxidant capacity (TPC=152.8±0.8 mg/g and DPPH=73.8±1.3 %).Conclusion: This study revealed that the essential oil was rich in camphor/chrysanthenyl acetate chemotype and different polyphenols in the category of hydroxycinnamic acid derivatives. In addition, this research demonstrated that the aerial parts of this aromatic herb were various sources of oily components, especially essential fatty acids.

Background: Two species of genus Marrubium belonging to the family Lamiaceae, were studied for their volatile components.Methods: The essential oils were extracted from aerial parts of the plants through hydrodistillation using a Clevenger apparatus. Later, CG and CG-MS analysis were applied to assess the chemical components of the essential oils.Results: Analysis of the M. propinquum essential oil resulted in the identification of 22 components, representing 79.6% of the total essential oil that principally contained oleic acid (19%), b-caryophyllene (7.4%) and m-tolualdehyde (5.2%). In the case of M. parviflorum, 20 components were identified, representing 83% of the M. parviflorum essential oil, among them oleic acid (11.8%), a-pinene (10.2%) and germacrene D (9.8%) were the main compounds.Conclusion: Regarding the results of this study in both essential oils after the non terpenoids, sesquiterpene hydrocarbons possessed the uppermost portion of the oils. We found some similarities and differences between M. propinquum and M. parviflorum essential oils and also in comparison with other species of genus Marrubium which might be due to different parameters such as agrotechnical factors.

Background: Carotenoids are organic pigments with substantial applications in neutraceuticals, pharmaceuticals, cosmetics and food industries. Considering the importance of carotenoids, we aimed to isolate and identify a carotenoid-producing microorganism in the present study.Methods: Gram-negative, aerobic and rod-shaped archaeon, Halorubrum sp. TBZ112 (KCTC 4203 and IBRC-M 10773) producing carotenoids with circle and red colonies were isolated from Urmia Lake in Northwest Iran. Phenotypic characterization and molecular identification of isolate were also conducted. In order to study the ability of TBZ112 to produce carotenoids as well as the production profile, carotenoids were extracted using acetone-methanol solution (7: 3 v/v). Then, the carotenoid content of the extract was evaluated using UV spectroscopy and thin-layer chromatography (TLC). The carotenoid profile was analyzed using liquid chromatography-mass spectrometry (LC-MS) techniques.Results: The 16S rRNA analysis showed that TBZ112 had the highest similarity with Halorubrum chaoviator Halo-G*T (99.78%). The total carotenoid content of strain TBZ112 was found to be 11.7 mg/l. The LC-MS analytical results indicated that carotenoids that were produced included bacterioruberin, lycopene and b-carotene. Among them, bacterioruberin was predominant.Conclusion: Consequently, we can suggest that future studies should investigate this new and natural source for producing carotenoids

Background: Hospital-acquired infections are among the most significant reasons of human mortality world-wide which can be controlled by efficient application of suitable disinfectant for hospital setting. The main goal of the present study was to determine the efficacy of eight routinely used hospital disinfectants against clinical isolates.Methods: In our descriptive study, in the first step the antibiogram assay of 99 clinical isolates enterococci and Pseudomonas aeruginosa were determined. Then, minimum inhibitory concentration and minimum bactericidal concentration of isolates against Povidone Iodine 10%, Ethanol 70%, Savlon 3.2%, Deconex51Gastro, Procept Floor, Septo med, Surfanious and Gigasept AF were evaluated.Furthermore, the efficacy of disinfectants was reevaluated in presence of 5% (w/v) Bovine Serum Albumin.Results: The results showed that Septo med and Surfanious are the most and less potent disinfectants against clinical isolates, respectively. It is also resulted that Povidone Iodine is the most effective choice among the conventional disinfectants in this study.Clearly, addition of 5% organic substances reduced the efficacy of selected disinfectants significantly.Conclusion: Novel quaternary ammonium compounds are the most applicable choice for disinfection of hospital surfaces and instruments in this study.

Background: Today, traditional medicine is developed globally as an important source for health care of the world's population. The current study describes the antibacterial activity of thymus commercial products against both Gram-positive including Staphylococcus aureus, Streptococcus pyogenes and Gram-negative bacteria including Escherichia coli, Pseudomonas aeruginosa.Methods: Two commercial products of thymus with standard expiration date (and in three different batch numbers) including anti-aphthous spray and oral drop were purchased from the pharmacies of Tabriz city. Minimum Inhibitory Concentration (MIC) and disk diffusion are used to investigate the antibacterial efficiency of the mentioned products.Results: The results of disk diffusion method showed zones of growth inhibition against S. aureus and S. pyogenes for the investigated products. Based on MICs, thymus oral drop had inhibitory effects against S. aureus, S. pyogenes while anti-aphthous spray showed inhibitory effects against S. aureus, S. pyogenes and P. aeruginosa. The findings also indicated that the thymus anti-aphthous spray had more inhibitory effects than thymus oral drop.Conclusion: This study showed that thymus can be used as an optimistic antibacterial agent against the selected microorganisms.