Iranian Journal of Pharmaceutical Research
Year:2015 | Volume:14 | Issue:1|Papers Count:35

Information plays a vital role in effective management of any system. With the Health Management Information System (HMIS), specific information may be provided to support the decision makers at various levels of the health system to assist evidence-based decision making. It is almost three decades (from 1984) that Iranian Ministry of Health (MoH) has used HMIS in its pharmaceutical sector as a mean to have an efficient regulation. Pharmaceutical distributor companies have reported their sales data to MoH at monthly intervals. Each company should report its data by 5th of each month. “ Iranian MoH Annual Pharma Statistics” or “ Amarnameh daruee Iran” will be published as software after combining this data with other related data and statistical analysis. This database is a basis for deciding issues of many policy makers, and management possesses in pharmaceutical sector. After an efficient coordination between MoH and distributors, each company reports its data in a defined format including some detailed information. Table 1 shows a sample chart of characteristics for this HMIS. Each pharmaceutical product in each city/each month has one record. For each product with brand name, the specific code will be used. If there is not any code for branded products, it is very important to get feedback to MoH to solve such problems. Figure 1 is a sample file format of a hypothetical company named XY to show more details. Until 1998 this information was reported as a manual printed database. From 1998 to 2003 it was reported as a book, and since 2003 the electronic database including data since 1998 has been published....

We developed biofunctionalized nanoparticles with magnetic properties by immobilizing diethyleneglycol (DEG) on Gd2O3, and PEGilation of small particulate gadolinium oxide (SPGO) with two methoxy-polyethyleneglycol-silane (mPEG-Silane 550 and 2000 Da) using a new supervised polyol route, described recently. In conjunction to the previous study to achieve a high quality synthesis and increase in the product yield of nanoparticles; assessment of the effects of functionalization, chemisorption and altered reaction conditions, such as NaOH concentration, temperature, reaction time and their solubility, on size reproducibility were determined as the goals of this study. Moreover, the effects of centrifugation, filtration and dialysis of the solution on the nono magnetic particle size values and their stability against aggregation have been evaluated. Optimization of reaction parameters led to strong coating of magnetic nanoparticles with the ligands which increases the reproducibility of particle size measurements. Furthermore, the ligand-coated nanoparticles showed enhanced colloidal stability as a result of the steric stabilization function of the ligands grafted on the surface of particles. The experiments showed that DEG and mPEG-silane (550 and 2000 Dalton) are chemisorbed on the particle surfaces of Gd2O3 and SPGO which led to particle sizes of 5. 9 ± 0. 13 nm, 51. 3 ± 1. 46 nm and 194. 2 ± 22. 1 nm, respectively. The small size of DEG-Gd2O3 is acceptably below the cutoff of 6nm, enabling easy diffusion through lymphatics and filtration from kidney, and thus provides a great deal of potential for further in-vivo and in-vitro application.

The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of poorly water soluble bioactive constituent patchouli alcohol (PA) that can be used for the preparation of immediate release pellets formulation. Two commercially available grades poloxamer 188 (P 188) and poloxamer 407 (P 407) were selected, and solid dispersions (SDs) containing different weight ratio of PA and poloxamers, and the combination of P 188 and P 407 as dispersing carriers of ternary solid dispersions (tSDs) were prepared by a low temperature melting method and solidified rapidly by dropping into the 10-15 ° C condensing agent atoleine. Both PA/P 188 and PA/P 407 binary solid dispersions (bSDs) could remarkably promote the dissolution rate of PA, increasing approximately 16 times in bSDs with poloxamers in comparison with pure PA within 180 min. P188 contributed to a faster dissolution rate than P 407, however, P 407 had a better solubility. It is interesting to note that the incorporation of P 188 in PA/P 407 bSD pellets could strongly enhance the dissolution rate of PA. DSC and FTIR were used to explore the characteristics of PA-SD pellets. The enhancement of dissolution from the SDs may be attributed partly to the reduction in particle size in PA crystalline due to the formation of eutectic system with poloxamers. Moreover, a simple, accurate in-vitro dissolution test method for volatility drug was established, and the process of PA-SD pellets preparation was simple, rapid, cost effective, uncomplicated and potentially scalable.

The goal of this research is to determine the feasibility of loading rifampin into mesoporous silica nanoparticles. Rifampin was selected as a model lipophilic molecule since it is a welldocumented and much used anti tuberculosis drug. The mesoporous silica nanoparticles were prepared by using tetraethyl ortho silicate and cetyltrimethyl ammonium bromide (as surfactant). The prepared nanoparticles were characterized in terms of their particle size measurement and porosimetry. The results showed that the particle size is 218 ± 46 nm (mean ± SD) and surface area is 816 m2g-1. In order to load rifampin within the mesopores, adsorption experiments using three different solvents (methanol, water and dimethyl sulfoxide) were carried out. The loading procedure resulted in a significant improvement in the amount of rifampin loaded into mesoporous silica nanoparticles and methanol was found to be a suitable solvent, providing a drug entrapment efficiency of 52 %. Rifampin loaded nanoparticles underwent different invitro tests including, SEM and drug release. The in-vitro drug release was investigated using buffer phosphate (pH=7. 4). Regarding the drug release study, a biphasic pattern of release was observed. The drug-loaded mesoporous silica nanoparticles were capable of releasing 95% of their drug content after 24 h, following a faster release in the first four hours. The prepared rifampin loaded nanoparticles seem to have potential for use as a pulmonary drug delivery.

The present study deals with characterization of dispersions of a poorly water-soluble drug, celecoxib (CLX) in polyvinyl caprolactame– polyvinyl acetate– polyethylene glycol graft copolymer (Soluplus® (SOL)) prepared by different techniques. Dispersions of CLX in SOL at different ratios (2: 1, 1: 1, 1: 2, 1: 4 and 1: 6) were prepared by spray drying, conventional solvent evaporation and melting methods. The solid states of samples were characterized using particle size measurements, optical and scanning electron microscopy, XRPD, DSC and FT-IR. The Gordon-Taylor equation was used to predict the Tg of samples and the possibility of interaction between CLX and SOL. The solubility and dissolution rate of all samples were determined. Stability of samples was studied at ambient conditions for a period of 12 months. DSC and XRPD analyses confirmed amorphous state of drug in samples. Surprisingly dispersions of CLX: SOL with the ratio of 2: 1 and 1: 1 showed slower dissolution rate than CLX while other samples showed higher dissolution rate. At 1: 2 ratio the spray dried samples exhibited higher dissolution rate than corresponding samples prepared by other methods. However at higher SOL content (1: 4 and 1: 6), samples prepared by different methods showed similar dissolution profiles. The stability studies showed that there were no remarkable changes in the dissolution profiles and solid state of the drug after 12 months storage at ambient conditions. It was concluded that SOL was a proper carrier to enhance the dissolution rate of CLX. At high SOL ratios the method of preparation of dispersed samples had no effect on dissolution rate, whilst at low SOL content spray drying was more efficient method.

In this paper, differences in porosity, compressive strength and tablet-forming ability of carbamazepine crystals agglomerated under similar condition, but subjected to different drying temperatures are reported. The agglomerates were prepared by spherical crystallization method and thereafter dried without agitation at different temperature. An increased drying temperature did not affect the shape and structure texture of dried particles and did not cause them to fracture. Drying of particles at higher temperature suppressed the particle contraction as a consequence of fast evaporation and hence produced particles of larger mean diameter, higher porosity and thus lower compressive strength than those dried at lower temperature. Through a relationship with particle porosity, the drying rate also affected the ability of particles to form tablets.

A new series of 1, 2-diaryl-4, 5, 6, 7-tetrahydro-1H-benzo[d]imidazoles, possessing trimethoxyphenyl pharmacophore, were synthesized to evaluate their biological activities as tubulin inhibitors. Cytotoxic activity of the synthesized compounds 7a-f was assessed against several human cancer cell lines, including MCF-7 (breast cancer cell), HEPG2 (liver hepatocellular cells), A549 (adenocarcinomic human alveolar basal epithelial cells), T47D (Human ductal breast epithelial tumor cell line) and fibroblast. According to our results, HEPG2 seems to be the most sensitive, while MCF7 was the most resistant cell line to the compounds. All the compounds expect 7b, possessed satisfactory activity against HEPG2 with mean IC50 values ranging from 15. 60 to 43. 81 μ M.

The thiosemicarbazides 3a-c were appeared by reaction of the corresponding substituted hydrazides 1a-c with allylisothiocyanate 2. Synthesis of some novel 1, 2, 4-triazole-thiols 4a-c bearing a pyridyl unit using 1-(x-picolinoyl)-4-allyl-thiosemicarbazides (x = 2, 3, 4) in an alkaline solution, is reported. Also, the S-alkylation of triazole derivatives 5-7a-c is described. The structure of the synthesized compounds resulted from the IR, 1H and-13C NMR spectroscopy and elemental analysis data. The antibacterial studies to all of the synthesized compounds against B. cereus, E. coli, P. aeroginosa, S. aureus and E. faecalis as MIC values are reported. Some of these compounds such as 7a, 4a and 3a exhibited a good to significant antibacterial activity.

The microbial resistance has become a global hazard with the irrational use of antibiotics. Infection of drug-resistant bacteria seriously threatens human health. Currently, there is an urgent need for the development of novel antimicrobial agents with new mechanisms and lower levels of toxicity. In this paper, a series of (S, Z)-4-methyl-2-(4-oxo-5-((5-substitutedphenylfuran-2-yl) methylene)-2-thioxothiazolidin-3-yl)pentanoic acids via a Knoevenagel condensation were synthesized and evaluated for their antibacterial activity in-vitro. The synthesized compounds were characterized by IR, 1H NMR and MS. The antibacterial test in-vitro showed that all of the synthesized compounds had good antibacterial activity against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 2– 4 μ g/mL. Especially compounds 4c, 4d, 4e and 4f were the most potent, with MIC values of 2 μ g/mL against four multidrug-resistant Gram-positive bacterial strains.

Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly, a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors. [6-hydrazinopyridine-3-carboxylic acid (HYNIC)-Tyr8-Met(O)11-SP] was synthesized and radiolabeled with 99mTc using ethylenediamine-N, N›-diacetic acid (EDDA)and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. Invivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity (>99%) and radiolabeled with 99mTc at high specific activities (84-112GBq/μ mol) with an acceptable labeling yield (>95%). The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. Invitro cell line studies on U373MG cells showed an acceptable uptake up to 4. 91 ± 0. 22% with the ratio of 60. 21 ± 1. 19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2. 46 ± 0. 43 nM and Bmax of 128925 ± 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3. 36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors.

The interaction between isatin-β-thiosemicarbazone (IBT) and calf thymus DNA (CT-DNA) was investigated in physiological buffer (pH 7. 4) using Neutral Red (NR) dye as a spectral probe by UV– Vis absorption and fluorescence spectroscopy, as well as viscosity measurements. The IBT is stabilized by intercalation in the DNA (K [IBT – DNA] = 1. 03×105 M− 1), and displaces the NR dye from the NR– DNA complex. The binding constants Kf and number of binding sites (n≈ 1) of IBT with DNA were obtained by fluorescence quenching method at different temperatures. Furthermore, the enthalpy and entropy of the reaction between IBT and CT-DNA showed that the reaction is enthalpy-favored and entropy-disfavored. The changes in the base stacking of CT-DNA upon the binding of IBT are reflected in the circular dichroic (CD) spectral studies. The viscosity increase of CT-DNA solution is another evidence to indicate that, IBT is able to be intercalated in the DNA base pairs.

Cerebral vasospasm considered to be a serious cause of morbidity and mortality following subarachnoid haemorrhage (SAH). Despite several available therapeutic options, current protocols do not prevent major consequences of vasospasm. Inflammation is believed to play an important role in post-haemorrhagic vasospasm. Meloxicam is a non-steroidal antiinflammatory drug. The aim of this study was to compare the efficacy of meloxicam versus placebo on vasospasm in patients with SAH. In this randomized, double-blind, placebocontrolled trial, SAH patients randomly received 7. 5 mg meloxicam or placebo twice daily for 7 days. End points were, middle cerebral artery velocity obtained with transcranial doppler, in-hospital mortality, hospital stay and discharge Glasgow Outcome Scale. Eighty-one patients enrolled in the study. (40 received meloxicam, 41 received placebo). Baseline characteristics were similar between the groups. There were no differences in length of hospitalization (17. 4 ± 3. 1 vs 18. 6 ± 4. 2 days; p = 0. 145), in-hospital mortality rate (15 vs 22%; p-value=0. 569), or GOS (p = 0. 972) between the two groups. MCA velocity were slightly less in patients who had received meloxicam, but not to a significant degree (p-value=0. 564(. No side effect has been detected for meloxicam. This study did not prove meloxicam efficacy in vasospasm of SAH patients. But it demonstrated that clinical trial of meloxicam in these patients is feasible and probably safe. The effectiveness of meloxicam on cerebral vasospasm has to be studied in larger trials.

Diabetes mellitus is the most common endocrine disorder, causes many complications such as micro-and macro-vascular diseases. Anti-diabetic, hypolipidemic and anti-oxidative properties of ginger have been noticed in several researches. The present study was conducted to investigate the effects of ginger on fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, and malondialdehyde in type 2 diabetic patients. In a randomized, double-blind, placebo-controlled, clinical trial, a total of 41 type 2 diabetic patients randomly were assigned to ginger or placebo groups (22 in ginger group and 19 in control group), received 2 g/day of ginger powder supplement or lactose as placebo for 12 weeks. The serum concentrations of fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I and malondialdehyde were analyzed before and after the intervention. Ginger supplementation significantly reduced the levels of fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein B/apolipoprotein A-I and malondialdehyde in ginger group in comparison to baseline, as well as control group, while it increased the level of apolipoprotein A-I (p<0. 05). It seems that oral administration of ginger powder supplement can improves fasting blood sugar, hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, apolipoprotein B/apolipoprotein A-I and malondialdehyde in type 2 diabetic patients. So it may have a role in alleviating the risk of some chronic complications of diabetes.

Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3′ , 4′-bis (substituted phenyl)-4′ H-spiro [indene-2, 5′-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes. 3D structures of the derivatives were docked into the colchicine binding site of tubulin using GOLD 5. 0 program under flexible ligand and semi-flexible receptor condition. The spiroisoxazoline derivatives bind tubulin in a similar manner to colchicine by establishing at least a hydrogen bonding to Cys241 as well as hydrophobic interactions with Leu255, Ile378 and Lys254 and few other residues at the binding pocket. It can be concluded that the spiroisoxazoline core structure common to the studied derivatives is a suitable scaffold for placing the antitubulin pharmacophoric groups in appropriate spatial positions required for tubulin binding activity.

Helicobacter pylori infection, the most common chronic bacterial infection in the world, and an important cause of gastrointestinal disorders, may be involved in the pathogenesis of some extra-gastrointestinal disturbances, as well as an increase in blood levels of certain inflammatory markers. Anti-bacterial activity against Helicobacter pylori and antiinflammatory properties of omega-3 fatty acids have been studied in several research studies. The purpose of the present study was the comparison of the effects of Eicosapentaenoic Acid and Docosahexaenoic Acid supplementation on Helicobacter pylori eradication, serum levels of some inflammatory markers and total antioxidant capacity. In a randomized, double-blind, placebo-controlled clinical trial, 97 Helicobacter pylori positive patients (64 patients in the two intervention groups and 33 in the control group), received 2 grams daily of Eicosapentaenoic Acid, Docosahexaenoic Acid or Medium Chain Triglyceride oil as placebo, along with conventional tetra-drug Helicobacter pylori eradication regimen, for 12 weeks. Helicobacter pylori eradication test and measurement of concentration of interleukine-6, interleukine-8, high-sensitivity C-reactive protein and total antioxidant capacity were performed after the intervention. There was no significant difference in eradication rate of the infection, levels of interleukine-6 and total antioxidant capacity among the three groups, while the levels of interleukine-8 and high-sensitivity C-reactive protein were statistically different. Eicosapentaenoic Acid or Docosahexaenoic Acid supplementation had no significant differential impact on the eradication of Helicobacter pylori infection, and serum levels of interleukine-6 and total antioxidant capacity. However, it had a desirable effect on the levels of interleukine-8 and high-sensitivity C-reactive protein in Helicobacter pylori positive patients.

Pre-menstrual syndrome is one of the most common disorders in women and impairs work and social relationships. Several treatment modalities have been proposed including herbal medicines. Considering the properties of wheat germ, this study aimed to determine the effects of wheat germ extract on the symptoms of premenstrual syndrome. This triple blind clinical trial was conducted on 84 women working in hospitals affiliated to Hamadan University of Medical Sciences. Subjects completed daily symptom record form for two consecutive months. After definitive diagnosis of premenstrual syndrome, they were randomly divided into two groups of 50 people. Then, for two consecutive months, 400 mg capsules of wheat germ extract or placebo were used three times a day, from day 16 until day 5 of the next menstrual cycle. Wheat germ significantly reduced physical symptoms (63. 56%), psychological symptoms (66. 30%), and the general score (64. 99%). Although the severity of symptoms decreased in both groups, this reduction was more significant in the wheat germ extract group (p < 0. 001). On the other hand, physical symptoms decreased only in the wheat germ extract (p < 0. 001) and there was no statistically significant difference in the placebo group. No complications were observed in any of the groups. It seems that using wheat germ extract reduces general, psychological and physical symptoms.

Clonidine has sedative and analgesic properties. Randomized studies examining these properties in mechanically ventilated ICU patients are scarce. This study was designed to assess the impact of clonidine on sedative agent use in mechanically ventilated patients. In a prospective, randomized, double blind, placebo-controlled study in a general ICU of a university medical center in Tehran, Iran, 40 patients, over 18 years on mechanical ventilation for 3 days or more randomized into 2 equal groups of clonidine and placebo. Clonidine arm received usual sedation and enteral clonidine 0. 1 mg TID and escalated to 0. 2 mg TID on the second day if hemodynamics remained stable. Ramsay Sedation Score was used to assess sedation. Opioids and midazolam were used in all patients. 10 patients in clonidine and 3 in placebo arms had history of drug abuse (P = 0. 018). The mean of sedatives used in the clonidine/placebo arms (mg/day) were; MED (Morphine Equivalent Dose) 91. 4 ± 97. 9/112. 1 ± 98. 8 P=0. 39, midazolam 7. 1 ± 7. 9/8. 3 ± 9. 2 P=0. 66 and propofol 535. 8 ± 866. 7/139. 1 ± 359. 9 P=0. 125. After adjusting for addiction and propofol, clonidine reduced MED use by 79. 6 mg/day (P=0. 005) and midazolam by 5. 41 mg/day (P = 0. 05). Opioids and midazolam need reduced by clonidine co-administration regardless of history of drug abuse. Acceptable side effect profile and the lower cost of clonidine could make it an attractive adjunct to sedative agents in ICU.

The manipulation of redox potential in secretory pathway by thiol reducing agents can be a strategy to improve the production levels of disulfide-bonded proteins including recombinant antibodies. Here we have studied the influence of cysteamine on viability and the production level of IgG4 in Sp2. 0 cells. For this purpose, the recombinant Sp2. 0 cells producing an anti CD33 IgG4, were subjected to different concentrations of cysteamine. At concentrations of 2, 4 and 5 mM cysteamine, the secreted levels of IgG4 did not change significantly. However, in concentration of 7 mM cysteamine, a significant decrease was observed in IgG4 levels which may indicate the cytotoxicity of this compound in higher concentrations. Our results show that the cysteamine treatment reduces the cell viability in a dose-dependent manner. Also it was observed that 2 mM cysteamine had no late effect on IgG4 production level and only at day 3, this concentration of cysteamine decreased the cell viability significantly. To test whether the addition of cysteamine can affect the expression level of protein disulfide isomerase, RTPCR analysis was carried out. The results revealed that cysteamine does not affect the PDI transcription and expression level of IgG4 in this type of recombinant cells.

Molecular farming has been considered as a secure and economical approach for production of biopharmaceuticals. Human TNF Related Apoptosis Inducing Ligand (TRAIL) as a promising biopharmaceutical candidate has been produced in different expression hosts. However, little attention has been paid to molecular farming of the TRAIL in spite of numerous advantages of plant expression systems. Therefore, in this study the cytoplasmic production of the TRAIL was tackled in Nicotiana tabacum using Agrobacterium tumefaciens LBA 4404. Initially, the desired coding sequence was obtained using PCR technique on the constructed human cDNA library. Afterward, the necessary requirements for expression of the TRAIL in plant cell system were provided through sub-cloning into 35S-CaMV (Cauliflower Mosaic Virus) helper and final 0179-pGreen expression vectors. Then, the final TRAIL-pGreen expression vector was cloned into A. tumefaciens LBA 4404. Subsequently, the N. tabacum cells were transformed through co-culture method and expression of the TRAIL was confirmed by western blot analysis. Finally, the recombinant TRAIL was extracted through chromatographic technique and biological activity was evaluated through MTT assay (Methylthiazol Tetrazolium Assay). The result of western blot analysis indicated that only monomer and oxidized dimer forms of the TRAIL can be extracted from the N. tabacum cells. Moreover, the lack of trimeric assembly of the extracted TRAIL diminished its biological activity in sensitive A549 cell line. In conclusion, although N. tabacum cells can successfully produce the TRAIL, proper assembly and functionality of the TRAIL were unfavorable.

Mycobacterium tuberculosis, the main cause of tuberculosis (TB), has still remained a global health crisis especially in developing countries. Tuberculosis treatment is a laborious and lengthy process with high risk of noncompliance, cytotoxicity adverse events and drug resistance in patient. Recently, there has been an alarming rise of drug resistant in TB. In this regard, it is an unmet need to develop novel antitubercular medicines that target new or more effective biochemical pathways to prevent drug resistant Mycobacterium. Integrated study of metabolic pathways through in-silico approach played a key role in antimycobacterial design process in this study. Our results suggest that pantothenate synthetase (PanC), anthranilate phosphoribosyl transferase (TrpD) and 3-isopropylmalate dehydratase (LeuD) might be appropriate drug targets. In the next step, in-silico ligand analysis was used for more detailed study of chemical tractability of targets. This was helpful to identify pantothenate synthetase (PanC, Rv3602c) as the best target for antimycobacterial design procedure. Virtual library screening on the best ligand of PanC was then performed for inhibitory ligand design. At the end, five chemical intermediates showed significant inhibition of Mycobacterium bovis with good selectivity indices (SI) ≥ 10 according to Tuberculosis Antimicrobial Acquisition & Coordinating Facility of US criteria for antimycobacterial screening programs.

This study aimed to determine biological activity and phytochemical study of Scutellaria platystegia (family Labiatae). Methanolic (MeOH) extract of aerial parts of S. platystegia and SPE fractions of methanolic extract (specially 20% and 40% methanolic fractions), growing in East-Azarbaijan province of Iran were found to have radical scavenging activity by DPPH (2, 2-diphenyl-1-pycryl hydrazyl) assay. Dichloromethane (DCM) extract of this plant exhibited animalarial activity by cell free method providing IC50 at 1. 1876 mg/mL. Crude extracts did not exhibit any toxicity assessed by brine shrimp lethality assay. Phytochemical study of methanolic extract by using reverse phase HPLC method and NMR instrument for isolation and identification of pure compounds respectively, yielded 2-(4-hydroxy phenyl) ethyl-O-β-D-glucopyranoside from 10% and apigenin 7-O-glucoside, verbascoside and martynoside from 40% SPE fraction. Occurance of verbascoside and martynoside as biochemical markers appeared to be widespread in this genus. Antioxidant and antimalarial activity of MeOH and DCM extracts, respectively, as well as no general toxicity of them could provide a basis for further in-vitro and in-vivo studies and clinical trials to develop new therapeutical alternatives.

Rosa damascena, Tripleurospermum disciforme and Securigera securidaca were used as disinfectant agents and for treatment of some disease in folk medicine of Iran. The antimicrobial effects of different fractions of seeds extract of S. securidaca, petals extract of R. damascena and aerial parts extract of T. disciforme were examined against some gram positive, gram negative and fungi by cup plate diffusion method. The petroleum ether and chloroform fractions of S. securidaca showed antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa, while its methanol fraction had no antibacterial effects. R. damascena petals extract demonstrated antibacterial activities against Bacillus cereus, Staphylococcus epidermidis, S. aureus and Pseudomonas aeruginosa. T. disciforme aerial parts extract exhibited antimicrobial effects only against S. aureus and S. epidermidis. None of the fractions had any antifungal activities. Therefore, present study confirmed utility of these plants as disinfectant agents. Six flavonoids were isolated from T. disciforme: Luteolin, Quercetin-7-O-glucoside, Kaempferol, Kaempferol-7-O-glucoside, Apigenin and Apigenin-7-O-glucoside. The flavonoids and the antimicrobial activity of T. disciforme are reported for the first time.

This study represents the first report on the chemical composition and biological activity of Trifolium angustifolium var. angustifolium. The major components of the essential oil were identified as hexatriacontene (23. 0%), arachidic acid (15. 5%) and α-selinene (10. 0%). The main constituents of the fatty acid obtained from the petroleum ether extract were identified as palmitic acid (29. 8%), linoleic acid (18. 6%) and oleic acid (10. 5%). In particular, the water extract exhibited higher activity than α-tocopherol and BHT, which were used as standards in the ABTS cation radical scavenging assay and indicated higher inhibitory effect against acetylcholinesterase enzyme than the reference compound, galanthamine but exhibited weak activity in β-carotene bleaching, DPPH-free radical scavenging, and cupric-reducing antioxidant capacity assays. The petroleum ether extract exhibited higher activity than α-tocopherol which was used as standard in the β-carotene bleaching method at concentration 100 μ g/mL. The acetone extract exhibited higher activity than α-tocopherol which was used as standard cupric reducing antioxidant capacity (CUPRAC) method at 100 μ g/mL concentration The acetone and methanol extracts were active on all microorganisms tested with a small zone diameter indicating weak activity.

Euphorbia macrostegia or Persian wood spurge is one of the seventeen endemic plants of this genus in Iran. Three triterpenoids, 24-methylenecycloartan-3β-ol (1), butyrospermol (2) and cycloartenol (3) and three diglycerides, 1, 2-di-O-α-linolenoyl-sn-glycerol (4), 1-O-linoleoyl-3-O-palmitoyl-sn-glycerol (5) and 1-O-α-linolenoyl-2-O-palmitoyl-sn-glycerol (6) were isolated from the hexane soluble part of methanol-dichloromethane extracts of the aerial parts of Euphorbia macrostegia Boiss. The structures of all compounds were elucidated using different spectroscopy methods including, 1H NMR, 13C NMR, HSQC, HMBC, EI-MS and IR. The triterpenes and the unsaturated fatty acids moieties of the diglycerides isolated from the plant were reported previously to have analgesic, anticancer, bactericidal and antifungal activity. Here, we show that E. macrostegia is a new source for the above mentioned biologically active compounds.

The objective of this study was to observe the apoptosis-inducing effect and mechanism of baicalin on human cervical cancer HeLa cells. The inhibitory effect of baicalin on the growth of HeLa cells was measured by MTT assay, and cell proliferation and migration was analyzed by cell scratch assay. Morphological changes of apoptotic cells were viewed by the light microscope and electron microscope, and cell growth arrest was confirmed by flow cytometry. Moreover, Western blot was used for investigating the expression of apoptosis related proteins; spectrophotometry was used to examine Caspase-3 activation. Our results showed that baicalin could inhibit the proliferation of HeLa Cells via induction of apoptosis in a time and dosedependent manner (P<0. 01). Apoptotic signaling induced by baicalin was characterized by up-regulating Bax, Fas, FasL and Caspase-8 protein expression, and down-regulating of Bcl-2 protein expression. These results indicated that baicalin-induced apoptosis involved activation Caspase-3 in HeLa cells through the intracellular mitochondrial pathway and the surface death receptor pathway.

The objective of this study was to evaluate the anti-inflammatory and analgesic activities of the hydro-alcoholic extract of the pods of Astragalus hamosus (HAAH), a plant used in Iranian traditional medicine, and antinociceptive effects of different fractions in animal models. The anti-inflammatory effect was evaluated by the rat paw edema induced by formalin. Also the analgesic effect was examined by the acetic-acid-induced writhing response and hot plate test. The analgesic effects of chloroform, hexane, ethyl acetate and aqueous fractions were evaluated by the hot-plate method. The hydroalcoholic extract of Astragalus hamosus could reduce the edema in a dose-dependent manner (P<0. 05). In the acute phase, the result of 1000 mg/Kg and in the chronic phase, the result of 100 and 300 mg/Kg of the extract were more significant and comparable with the effect of sodium salicylate. Also application of different doses of HAAH had significant anti-nociceptive effects on both animal models. The findings showed that HAAH at doses of 700 and 1000 mg/Kg produced analgesic effects comparable to sodium salicylate. The hexane and ethyl acetate (but not the other fractions) showed significant analgesic activity in hot plate test, when compared to morphine. The results of this study demonstrated the antiinflammatory and analgesic effects of HAAH extract and hexane and ethyl acetate fractions of the extract in animal models and justify traditional use of this plant in the treatment of pain and inflammatory conditions. More studies to clarify the active components are necessary.

Previous studies demonstrated that CSE induces oxidative stress and its consequences on isolated mitochondria obtained from lung, heart and brain which may provide insight into the role of CSE in human health and disease. The present study was carried out to further characterize and compare toxic effect of CSE extract on isolated mitochondria obtained from either a directly contacting tissue (i. e. skin) or a vital visceral tissue (i. e. liver). We obtained Rat liver and skin mitochondria by differential ultracentrifugation and incubated the isolated mitochondria with different concentrations (1, 10 and 100%) ofstandardizedcigarette smoke extract (CSE). Our results were similar to our previous study which discovered CSE toxicity mechanisms on isolated mitochondria obtained from lung, heart and brain with minor changes. CSE induced a significant rise in ROS formation, lipid peroxidation and mitochondrial membrane potential collapse and mitochondrial swelling on isolated mitochondria obtained from both liver and skin. CSE induced Decrease in ATP concentration on isolated mitochondria obtained from both liver and skin did not include CSE lowest concentration (1%). Our findingsshowed that CSEinduced toxicity in liver and skin is due to disruptive effect on mitochondrial respiratory chain which canleads to cytochrome c release and apoptosis signaling.

Myocardial infarction (MI) is a common presentation of the ischemic heart disease. Lavandula angustifolia is an herbaceous plant with antioxidative effects. This study was designed to investigate the cardioprotective effects of lavandula angustifolia essential oil against isoproterenol-induced MI in rats. The dried sample was subjected to hydrodistillation by using a Clevenger and the oils were dried over anhydrous Na2SO4. Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol and treatment with 5, 10, 20 mg/Kg of the essential oil. MI was induced by subcutaneous injection of Isoproterenol (100 mg/Kg) for 3 consecutive days at an interval of 24 h. The essential oil was given intraperitoneally every 24 h started at MI induction. Following anesthesia, hemodynamic parameters were measured. After sacrificing the animals, the hearts were removed to measure the heart to body weight ratio and histopathological examination. Myeloperoxidase (MPO) and Malondialdehyde (MDA) were measured in heart tissues for evaluating the activity of neutrophils and lipid peroxidation, respectively. The essential oil amended ECG pattern by suppressing ST-segment elevation and increasing R-amplitude. 10 mg/Kg of the essential oil significantly decreased heart to body weight ratio (P<0. 001) and the elevation of MDA and MPO in myocardium, it also increased dp/dtmax from 2793 ± 210 to 4488 ± 253 mmHg/sec (P<0. 001), and 20 mg/Kg of it significantly lowered LVEDP from 14 ± 3. 43 to 4. 3 ± 0. 83 mmHg (P<0. 001). The results demonstrated that L. angustifolia protects myocardium against isoproterenol-induced MI that it could be related to its antioxidant properties.

Different treatment strategies of Alzheimer› s disease (AD) are being studied for treating or slowing the progression of AD. Many pharmaceutically important regulation systems operate through proteins as drug targets. Here, we investigate the drug target proteins in beta-amyloid (Aβ ) injected rat hippocampus treated with Lavandula angustifolia (LA) by proteomics techniques. The reported study showed that lavender extract (LE) improves the spatial performance in AD animal model by diminishing Aβ production in histopathology of hippocampus, so in this study neuroprotective proteins expressed in Aβ injected rats treated with LE were scrutinized. Rats were divided into three groups including normal, Aβ injected, and Aβ injected that was treated with LE. Protein expression profiles of hippocampus tissue were determined by two-dimensional electrophoresis (2DE) method and dysregulated proteins such as Snca, NF-L, Hspa5, Prdx2, Apoa1, and Atp5a1were identified by MALDI-TOF/TOF. KEGG pathway and gene ontology (GO) categories were used by searching DAVID Bioinformatics Resources. All detected protein spots were used to determine predicted interactions with other proteins in STRING online database. Different isoforms of important protein, Snca that exhibited neuroprotective effects by anti-apoptotic properties were expressed. NF-L involved in the maintenance of neuronal caliber. Hspa5 likewise Prdx2 displays as anti-apoptotic protein that Prdx2 also involved in the neurotrophic effects. Apoa1 has anti-inflammatory activity and Atp5a1, produces ATP from ADP. To sum up, these proteins as potential drug targets were expressed in hippocampus in response to effective components in LA may have therapeutic properties for the treatment of AD and other neurodegenerative diseases.

Different treatment strategies of Alzheimer› s disease (AD) are being studied for treating or slowing the progression of AD. Many pharmaceutically important regulation systems operate through proteins as drug targets. Here, we investigate the drug target proteins in beta-amyloid (Aβ ) injected rat hippocampus treated with Lavandula angustifolia (LA) by proteomics techniques. The reported study showed that lavender extract (LE) improves the spatial performance in AD animal model by diminishing Aβ production in histopathology of hippocampus, so in this study neuroprotective proteins expressed in Aβ injected rats treated with LE were scrutinized. Rats were divided into three groups including normal, Aβ injected, and Aβ injected that was treated with LE. Protein expression profiles of hippocampus tissue were determined by two-dimensional electrophoresis (2DE) method and dysregulated proteins such as Snca, NF-L, Hspa5, Prdx2, Apoa1, and Atp5a1were identified by MALDI-TOF/TOF. KEGG pathway and gene ontology (GO) categories were used by searching DAVID Bioinformatics Resources. All detected protein spots were used to determine predicted interactions with other proteins in STRING online database. Different isoforms of important protein, Snca that exhibited neuroprotective effects by anti-apoptotic properties were expressed. NF-L involved in the maintenance of neuronal caliber. Hspa5 likewise Prdx2 displays as anti-apoptotic protein that Prdx2 also involved in the neurotrophic effects. Apoa1 has anti-inflammatory activity and Atp5a1, produces ATP from ADP. To sum up, these proteins as potential drug targets were expressed in hippocampus in response to effective components in LA may have therapeutic properties for the treatment of AD and other neurodegenerative diseases.

Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0. 001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0. 001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0. 001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life.

As in Iranian traditional medicine, bee venom (BV) is a promising treatment for the rheumatoid arthritis (RA) which is considered as a problematic human chronic inflammatory disease in the present time. Smoking is considered to be a major risk factor in RA onset and severity. The main aim of this study is to investigate the effects of BV on cigarette smokeinduced inflammatory response in fibroblast-like synoviocytes (FLS). Cytotoxicity of cigarette smoke condensate (CSC) and bee venom were determined by the tetrazolium (MTT) method in cultured synovial fibroblastes. The expression of interleukin-1β and sirtuin1 mRNA were analyzed by SYBR green real-time quantitative PCR. Differences between the mean values of treated and untreated groups were assessed by student t-test. Based on MTT assay, CSC and BV did not exert any significant cytotoxic effects up to 40 μ g/mL and 10 μ g/mL, respectively. Our results showed that interleukin-1β mRNA level was significantly up-regulated by CSC treatments in LPS-stimulated synoviocytes in a dose-dependent manner. Conversely, the expressions of IL-1β and Sirt1 were up-regulated even in lower concentrations of BV and attenuated at higher concentrations. Also, BV attenuated the CSC-induced and LPS-induced inflammatory responses in synovial fibroblasts. Our results support the epidemiological studies indicating pro-inflammatory effects of CSC and anti-inflammatory effects of BV on FLS cell line.

Intraplatelet vasodilator-stimulated phosphoprotein (VASP) analysis is a commonly used laboratory approach for monitoring of the anti-platelet therapy with adenosine diphosphate (ADP) receptor blocking agents; however, it’ s testing in clinical laboratory needs a high level of experience and proficiency. The ability to recognize how the pre-analytical variations can change the results would be helpful for the interpretation of data from intraplatelet VASP analysis. The aim of this study was to describe the possible differences of intraplatelet phospho-VASP expression between washed and platelet rich plasma (PRP) samples, both at baseline levels and following experimentally induction of VASP phosphorylation. PRP and washed platelet samples were treated with different inducers of VASP phosphorylation, including forskolin (10 μ M), prostaglandin E1 (PGE1) (50 nM) and sodium nitro-prusside (SNP) (100 μ M). Untreated PRP and washed platelet samples were also included in study as baseline controls. After labeling of platelets with either anti P-Serine157-VASP or anti P-Serine239-VASP, the samples were subjected to flow cytometric analysis to monitor the levels of intraplatelet phospho-VASP expression. Washed platelet samples tend to show increased expression of intraplatelet P-Serine157-VASP at baseline state and also more expression of P-Serine157-VASP and P-Serine239-VASP in response to forskolin and SNP, compared with PRP samples. Though, reduced levels of PGE1-induced VASP phosphorylation at both residues were detected for washed platelets. In this study we have provided some background information required for performing of intraplatelet VASP analysis on differently handled platelet samples and interpretation of the obtained results.

Grape seed proanthocyanidin extract (GSPE) has a broad spectrum of biologic properties against oxidative stress. This study aimed to investigate the effects of GSPE on biochemical factors and antioxidant enzymes of erythrocyte in diabetic rats. Diabetes was induced through single injection of streptozotocin (50 mg. Kg-1, i. p). Forty Male Sprague-Dawley rats were divided into four Groups: Group 1, healthy control group; Group 2, healthy group treated with GSPE (200 mg. Kg-1); Group 3, diabetic control group; Group 4, diabetic group treated with GSPE (200 mg. Kg-1) for 4 weeks. At the end, the experimental animals were sacrificed and blood samples were collected and plasma parameters and erythrocytes antioxidant status were evaluated. The results show, treatment with GSPE significantly reduced (P<0. 001) urine volume, proteinuria and biochemical factors such as blood urea nitrogen, creatinine, triglyceride, total cholesterol, low density lipoprotein and very low density lipoprotein as well as malondialdehyde. Also GSPE treatment significantly (P<0. 005) increased high density lipoprotein, total protein and albumin. Moreover GSPE significantly increased antioxidant enzymes activity such as: superoxide dismutase, glutathione peroxidase and catalase. These results suggest that GSPE can ameliorate biochemical abnormalities and antioxidant system status in streptozotocin-induced diabetic rats probably by its potent antioxidant features.

This study was conducted to assessthe preventive effect of aqueous extract of Berberis integerrima Bge. root (AEBIR) on liver damage and oxidative stress induced by diabetes mellitus in rats. Forty male rats were divided into 5 groups as follows: 1-normal (N); 2-normal + barberry (N+B) (they received barberry root extract for 6 weeks); 3-diabetic (D) (they received Streptozotocin (STZ), 65 mg/Kg BW /i. p. ); 4-diabetic +barberry before (D+Bb) (they received barberry root extract for 3 weeks before STZ injection and continued for another three weeks); and 5-diabetic + barberry after (D+Ba) (three days after STZ injection, they received barberry root extract for 3 weeks). The experimental groups received barberry root extract (500 mg/Kg bw) intra gastric by gavage for 6 weeks. The treatment of diabetic rats with AEBIR showed a significant decreases(p<0. 001) in levels of blood glucose, malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin while body weight, total protein, superoxide dismutase (SOD), catalase(CAT) and reduced glutathione (GSH) increased (p<0. 001) in comparison to diabetic control rats. Consumption of AEBIR in group D+Bb caused significant improvement in all these factors, compared to the group D+Ba. Also in this study, for the first time, we demonstrated that administration of AEBIR before diabetes induction resulted in enhanced amelioration of liver complications compared to the group receiving it after induction, indicating that AEBIR can play a preventive role in such patients.