Iranian Journal of Pharmaceutical Research
Volume:17 Issue: 2, Spring 2018

Wharton’s jelly mesenchymal stem cells (HWJMSCs) hold promise for myocardial regeneration, but optimal treatment regimen (preferably with a growth factor) is required to maximize functional benefits. The aim of this study was to explore the cardioprotective and angiogenesis effects of HWJMSCs combined with insulin-like growth factor-1 (IGF-1) in the treatment of acute myocardial infarction.
The hydrogel consisted of Polyethylene glycol (PEG) and hyaluronic acid was prepared and characterized with regards to rheology, morphology, swelling, degradation, and release behaviors. To examine in vivo effects, the hydrogels containing HWJMSCs either alone (Cells/hydrogel group) or with IGF-1 (Cells/hydrogel/IGF-1 group) were intra-myocardially injected into a rabbit myocardial infarction model. In vivo efficacy was evaluated histological, immunohistochemical, echocardiography, scanning electron microscopy, and SPECT analyses. Eight weeks after infusion, the Cells/hydrogel and Cells/hydrogel/IGF-1 groups exhibited significantly increased left ventricular ejection fraction by echocardiography. Percent of ejection fraction were respectively 18.5% and 40% greater than control (P

In this study, N,N-Dimethyl-N-Octyl chitosan was synthesized. Nanoparticles containing insulin were prepared using PEC method and were statistically optimized using the Box-Behnken response surface methodology. The independent factors were considered to be the insulin concentration, concentration and pH of the polymer solution, while the dependent factors were characterized as the size, zeta potential, PdI and entrapment efficiency. The optimized nanoparticles were morphologically studied using SEM. The cytotoxicity of the nanoparticles on the Caco-2 cell culture was studied using the MTT cytotoxicity assay method, while the permeation of the insulin nanoparticles across the Caco-2 cell monolayer was also determined. The optimized nanoparticles posed appropriate physicochemical properties. The SEM morphological studies showed spherical to sub-spherical nanoparticles with no sign of aggregation. The in-vitro release study showed that 95.5 ± 1.40% of the loaded insulin was released in 400 min. The permeability studies revealed significant enhancement in the insulin permeability using nanoparticles prepared from octyl chitosan at 240 min (11.3 ± 0.78%). The obtained data revealed that insulin nanoparticles prepared from N,N-Dimethyl-N-Octyl chitosan can be considered as the good candidate for oral delivery of insulin compared to nanoparticles prepared from N,N,N-trimethyl chitosan.

Poor bioavailability of ophthalmic drops is mainly due to drainage through the nasal-lacrimal duct and a very low permeability through corneal epithelium. The aim of our study was to prepare and characterize an ocular hydrogel of loratadine, as an example of a lipophilic drug, to increase drug concentration and residence time at the site of action in the eye. In this study,a 23full factorial design was employed to design and compare the properties of eight different loratadine - containing hydrogel formulations. Results showed a significant correlation between the swelling and porosity ratios of the hydrogels and the Pluronic percentage and Pluronic/carbomer ratio in the formulations. Moreover, the release profiles showed fast and sustained release of all the formulations. Evaluation of hydrogels structure by the FT-IR technique indicated that Pluronic interacts with hydroxyl and carboxylic groups in carbomer, which is the main reason for the hydrogel network formation and interacts with loratadine.The permeation of loratadine through rabbit cornea showed that drug permeation percentages for the F2 and F7 formulations were 15 and 70 folds more than that of the control.

The objective of this study was to develop a novel bacterially-triggered micro-particular system of de-esterified tragacanth (DET) in combination with Eudragit S-100 coated capsules for colon drug delivery of 5-fluorouracil (5-FU) using microemulsion method. The loading study was conducted at different drug-to-polymer ratios and cross-linker concentrations. The maximum loading efficiency was achieved, 44.1% at 1:5 drug-to-polymer ratio and 0.7% cross-linker concentration. The FTIR results also confirmed the encapsulation of 5-FU in microspheres.
The release profile was dependent on the cross-linker concentration, environmental pH, and presence of pectinase enzyme. Microspheres inserted into Eudragit S-100 coated capsules released less than 5% of the drug at stomach and small intestine pH levels, whereas 70% of the drug was released at colon pH levels, and about 25% of the drug did not release unless in the presence of pectinase enzyme. To omit burst release, microspheres were washed with water, and the release became pH independent, and was just achieved in the presence of pectinase enzyme. 5-FU loaded microspheres with an IC50 value of 80 µg/mL were as effective as the free drug on HT-29. Generally, the results demonstrated that drug-loaded microspheres inserted into Eudragit S-100 coated capsules can be effective for colon-targeted delivery.

Co-delivery approach has been recommended to reduce the amount of each drug and to achieve the synergistic effect for cancer treatment. CUR and SF have antitumor effects, but their application is limited because of their low water solubility and poor oral bioavailability. To improve the bioavailability and solubility of SF and CUR, we performed an innovative co-delivery of SF and CUR with magnetic nanoparticles to endorse SF and CUR maintenance as an effective and promising antitumor drugs. The structure of the synthesized nanocarrieris evaluated by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, vibrating sample magnetometer, dynamic light scattering and Fourier transform infrared spectroscopy. The results revealed that the zeta potential of CUR and SF-loaded NPs were about -15.4 mV and the average sizes were 80.57 nm. They were monodispersed (polydispersity index =0.161±0.016) in water, with high drug-loading capacity and stability. CUR and SF were encapsulated into NPs with loading capacity of 19.32 ± 0.023% and 18.74 ± 0.015% and entrapment efficiency of 83.72 ± 0.14% and 81.20 ± 0.18% respectively. The in-vitro study of SF and CUR loaded PEGylated Fe3O4@Au NPs on human breast adenocarcinoma cell line (MCF-7) confirmed that cytotoxicity of SF and CUR can enhance when they are loaded on PEGylated Fe3O4@Au NPs in comparison to free SF and CUR. The results of flow cytometry and real-time PCR shown that this combination can increase therapeutic effects of SF and CUR by apoptosis and necrosis induction as well as inhibiting of migration in MCF-7 cell line.

The objective of this research was in-vitro germination and callus induction of Onosma bulbotrichum (O. bulbotrichum) as a medicinal herb which belongs to Boraginaceae family. For germination, the seedswere cultured on growth regulator-free MS medium and for callus induction, seeds were sown on modified MS medium containing different concentrations of kinetin (kn)- Indole-3-acetic acid (IAA) and kn- 2,4-D (2,4-dichlorophenoxyacetic acid), respectively. The plates were maintained in the dark at growth chamber. After 7 days seed germination on hormone-free medium and after 10 days callus initiation on modified medium in the presence of hormones was occurred. The maximum pigmented callus (100%) was observed on modified MS medium with a combination of 0.2 mg.L-1 IAA 2.10 mg.L-1 kn. Shikonin determination was performed by HPLC method. In addition, total hydroxynaphtoquinons as polyphenols in sum of callus and culture medium were measured by spectrophotometric method and revealed that total naphtoquinones content at IAA was more than 2, 4-D.

A common approach in resolving enantiomers of chiral basic drugs by capillary electrophoresis (CE) is to use cyclodextrins (especially their anionic derivatives) as chiral selector in the acidic buffer (pH ≤ 3) in normal or reversed (carrier) mode. Then, some organic modifiers are added to the buffer solution if the resolution is not satisfactory. In case of cetirizine (CTN), applying the same approach, i.e. a reversed mode capillary zone electrophoresis (CZE) method with an acidic buffer and sulfated-b-cyclodextrine (S-bCD) as chiral selector, was failed and no complete enantioseparation was achieved. Different organic modifiers, like urea and triethylamine HCl, were used to improve chiral resolution which led to partial resolution of the two peaks. Then, guanidine HCl at a concnetration of 100 mM was added to the running buffer and an acceptable resolution of the enantiomers of the drug was obtained. The method was successfully applied to determine optical purity of a levo-cetirizine (l-CTN) sample.

Due to the unique optical properties like high brightness and narrow emission bands of Quantum dots, it is used as simple fluorescence materials in bio-imaging, immunoassays, microarrays, and other applications. To easy invistigate cell lines that overexpressed somtostatin receptors, somatostatin (SST) was conjugated with Quantum dots carrying PEG amine (Qdots-PEG-NH2). The conjugation of SST to Qdots-PEG-NH2 started with the thiolation of SST using Traut’s reagent. Moreover, the Qdots-PEG-NH2 were subsequently activated by 500-fold molar excess of sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC) dissolved in phosphate buffer. The Qdots-PEG-NH2-sulfo-SMCC was conjugated to the thiolated-SST to form Qdots-SST. The number of sulfhydryl groups can be controlled by the molar ratio of Traut´s reagent to SST. Thiolation was necessary for the conjugation of SST to Qdots-PEG-NH2. This was achieved by reacting the SST with Traut’s reagent in a 1:1 molar ratio. Ellman’s reagent was used to determine the number of sulfhydryle groups. Furthermore, cellular uptake study on Triple negative breast cancers cells (HCC-1806) showed that the number of Qdots-SST per cell were significantly higher compared to unmodified Qdots-PEG-NH2 when quantified using inductively coupled plasma optical emission spectroscopy (ICP-OES). Moreover, the binding of Qdots-SST to cells can be suppressed by addition of antagonist, indicating that the binding of Qdots-SST to cells due to receptor-specific binding.

A simple, efficient, and environmentally friendly method has been developed for the synthesis of a series of tricyclic fused pyrazolopyranopyrimidines via a one-pot three-component reaction of barbituric acids, aromatic aldehydes, and 3-methyl-5-pyrazolone in the presence of SBA-Pr-SO3H. SBA-15 mesoporous silica material functionalized with propyl sulfonic acid groups was used as a heterogeneous Brønsted acid catalyst with hexagonal structure, high surface area, thick walls, and large uniform pores. All reactions were performed under reflux conditions in water in the presence of a catalytic amount of SBA-Pr-SO3H. High yields, mild reaction conditions, short reaction times, and simple work-up procedures are some advantages of this method. The antimicrobial activities of the synthesized compounds were also evaluated and some products exhibited significant antibacterial activities at low concentrations.

Organophosphate pesticides are considered as endocrine disruptors that interfere with reproductive functions. The corpus luteum (CL) is a transient endocrine gland that produces progesterone, a crucial hormone for a successful beginning and maintenance of pregnancy. Steroidogenic acute regulatory protein (StAR) facilitates the rate-limiting transfer of cholesterol from the outer mitochondrial membrane to the inner organelle membranes. We investigated the effect of Diazinon (DZN), an organophosphate, on StAR mRNA expression by Sybergreen Real Time-PCR in a time-dependent manner in luteal phase. Fifty immature female Wistar rats (24-day-old) were injected with a single injection of Pregnant mare’s Serum Gonadotropin (PMSG) followed by a single injection of human Chorionic Gonadotropin (hCG), 48 hr later. Then, DZN was administered in a single dose (70 mg/kg bw, I.P); controls received only the vehicle, 12 hr post-hCG injection. Ovaries were collected in 4-hr intervals from 8 to 24 hr post-hCG injection. After, hCG stimulation transcript level of StAR gene were significantly altered in the hormone-stimulated rats following DZN treatment. In addition, histological study showed that the CL diameter in DZN-treated group was smaller than control group (p = 0.000). Our findings suggest that the critical step in the function of CL is disrupted by DZN and may correlates with female reproductive damage.

Methamphetamine (MA), a highly addictive psychostimulant, produces long-lasting neurotoxic effects well proven in nigrostriatal dopaminergic neurons. Considering the similarities between pathological profile of MA neurotoxicity and Parkinson's disease (PD), some reports show that previous MA abusers will be at greater risk of PD-like motor deficits. To answer the question if repeated MA exposure causes parkinsonian-like behavior in rats, we used three regimens of MA administration and assessed the motor performance parameters immediately and over a long period after MA discontinuation. Male Wistar rats in two experimental groups were treated with escalating paradigms consisting of twice daily intraperitoneal injection of either 1-7 mg/kg or 1-14 mg/kg of MA over 14 days. The third group received twice-daily doses of 15 mg/kg of MA every other day for total number of 7 days. At the 1st, 7th, 14th, 21st, 28th, and 60th days after last injections, motor activities were evaluated using narrow beam, pole, and rotarod tests. Locomotor activity was also evaluated using open field test. Repeated-measures ANOVA indicated that over the two months period following MA exposure, drug-treated rats perform beam, pole, and rotarod tests equally well as their corresponding vehicle-treated controls. Comparison of the locomotor activity didnt show significant differences between groups. These data indicated that MA at these regimens does not cause PD-related motor deficits in rats. Since MA doses, exposure duration, and dosing intervals have been shown to affect MA-induced dopaminergic toxicity, it can be concluded that none of these regimens; are strong enough to produce measurable behavioral motor deficits in rat.

Crocin, the main constituent of saffron (Crocus sativus L.), is a natural carotenoid which is known for its antioxidant activity. Liver as the organ that metabolizes many chemicals is one of the first position that is at risk of environmental pollutants. It is clear that compounds that exhibit antioxidant properties, scavenging of free radicals and inhibition of lipid peroxidation are expected to show hepatoprotective effects. Previous studies have proven the protective effect of crocin on the liver. The aim of this study is to find out the exact hepatoprotective mechanisms of this compound.
In the present study, the protective effects of various concentrations of crocin (5, 10, 25, 50 and 100 μg/mL) were examined against oxidative stress toxicity induced by cumene hydroperoxide (CHP) on isolated rat hepatocytes. To find out the exact protective activity of crocin, we evaluated cell lysis, lipid peroxidation, reactive oxygen species (ROS) generation, GSH/GSSG, collapse of mitochondrial membrane potential, lysosomal membrane damage, the release of cytochrome c, and cellular proteolysis.
Crocin (50 and 100 µg/mL) reduces cell lysis, lipid peroxidation, ROS generation, collapse of mitochondrial membrane potential, lysosomal membrane damage, cytochrome c release, and cellular proteolysis. It also increase GSH/GSSG.
Crocin (50 and 100 µg/mL) reduced liver toxicity not only as an antioxidant but also by protecting the mitochondria and lysosome. Our data demonstrated that crocin is a promising candidate for preventing liver injury associated with oxidative stress. These findings pave the way to further studies evaluating the clinical protective effect of crocin.

The contamination of melamine was evaluated in 69 infants along with follow up formula samples collected from the market for the first time in Iran using HPLC method. Since there are no previous data concerning the contamination level of melamine in all brands of infant formula samples consumed using the HPLC method in Iran, this study is the first investigation in this regard. Our results showed that melamine contamination was found in 65% of samples, where mean and maximum levels of melamine were 0.73 ± 0.71 mg/kg and 3.63 mg/kg, respectively. The level of melamine in 10 out of 69 samples was higher than the maximum level set by the Codex Alimentarius in infant food (1 mg/kg). Melamine was determined in 67.8% and 50% of domestic and imported samples, respectively. The estimated daily intake was designed in two scenarios: it was calculated based on the mean level of melamine contamination and maximum level of melamine in the samples. In both scenarios, our results showed that melamine intake across all age groups is lower than the tolerable daily intake (TDI) of 0.2 mg/kg body weight, suggested by WHO (0.2 mg/kg body weight). Thus, it seems that the current levels of melamine in infant and follow up formula purchased in Iran pose no health risk for infants.

In current study, the effects of Iranian rice cooking method (Kateh) on residue levels of 41 pesticides were investigated. The pesticides were selected according to Iranian National Standards Organization (INSO) regulations and covered 18 permitted and 23 banned pesticides belonging to different chemical classes such as organophosphate, triazole, and carbamate. A 250 g portion of rice sample was soaked in 2.5 L spiked tap water containing studied pesticides at final concentration 2 μg/mL and then, the effects of washing and cooking were investigated. The pesticides were analyzed simultaneously in a single run using positive electrospray ionisation with multiple reaction monitoring (MRM) after extraction with QuEChERS method. The results showed that washing removed different portions of pesticide residues in the range between 12.0-88.1%. Washing effect was not associated with the water solubility of the pesticides but amount of residue binding to rice matrix was a major factor for residue reduction. In Iranian method of rice preparation, cooking process includes boiling and steam cooking. In this study, the amount of the pesticide residues was decreased in the range of 20.7-100%. Under these conditions, volatilization, hydrolysis, and thermal degradation caused the reduction of the pesticide residues.

Due to hygienic risks of mercury residues in food and marine originated supplements, measuring total mercury and methyl mercury contents of canned tuna as a highly consumable marine food product is essential. In this study, 40 canned Tuna fish (from Persian Gulf) were collected in 2015 and then flame atomic absorption spectrometer (FAAS) and thermo gas chromatography mass spectrophotometry were used to measure total mercury and methyl mercury, respectively. The results indicated that the average contents of total mercury and methyl mercury of the canned tunas, with 34.2 and 29.5 ppb decrements compared with 2009's measurement, were 177.4 and 143.7 ppb respectively. The highest concentration of the total mercury was 315.2 while it was 267.9 ppb for methyl mercury. This study showed that the content of the mercury in canned tunas of the Persian Gulf was less than the Maximum Residue Limit (MRL).

The 4-ACGC isolated from BP was prepared to investigate the cardioprotective effects on attenuating chronic heart failure in vivo and in vitro. A chronic heart failure (CHF) rat model was established to investigate the cardioprotective effects of 4-ACGC. From this, several cardiac function indexes were recorded. The inflammatory markers including tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1β (IL-1β) were evaluated by enzyme-linked immunosorbent assay (ELISA). Subsequently, serum levels of myocardial enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) were also assessed by ELISA kits. Ultimately, the cardioprotective and anti-inflammatory effects of 4-ACGC were further verified on CMECs. The results showed that the treatment of 4-ACGC significantly reduced cardiac hypertrophy and reversed the Ejection Fraction (EF), Heart Rate (HR), Fractional Shortening(FS) and Cardiac Output (CO) changes in CHF rats. The treatment of 4-ACGC could effectively inhibit the inflammatory cytokines induced by CHF. It’s also showed that a reverse effect of 4-ACGC on serum increased levels of LDH and CK in CHF rats. The increased levels of IL-1β and IL-6 stimulated by TNF-α on CMECs were also decreased after treating with 4-ACGC. The present study provided experimental evidence that 4-ACGC possessed obvious cardioprotective effects on attenuating CHF. 4-ACGC could suppress the expression of inflammatory mediators and myocardial enzymes, which might be one of the mechanisms.

One of the most common causes of mortality in acute kidney injury is brain dysfunction. Here we investigated the possible protective effect of erythropoietin (EPO) on cognitive impairments induced by bilateral renal ischemia (BRI).
Eighty male Wistar rats were allocated into 8 groups: 1, 2) Sham (Vehicle), 3, 4) Shamჳ, 5, 6) BRI, 7, 8) BRIჳ. The groups followed by the reperfusion periods of 24hours (24h) and 1week (1w). EPO or saline was administrated 30 min before surgery (1000 IU/kg, i.p.). The cognitive function was assessed by passive avoidance learning and Morris water maze tests. Hippocampal brain-derived neurotrophic factor (BDNF) protein expression was assessed by western blotting.
BUN (blood urea nitrogen) and creatinine (Cr) concentrations were significantly increased in BRI group 24h after reperfusion. BRI rats had just an increased level of BUN but not Cr 1w after reperfusion. EPO reversed passive avoidance learning impairments observed in BRI group 24h after reperfusion. There were no significant differences in spatial and passive avoidance learning between experimental groups 1w after reperfusion and histological evaluation confirmed the behavioral data. BRI decreased significantly the BDNF protein expression in the hippocampus and EPO increased that 24h after operation.
These observations showed protective effect of EPO against cognitive dysfunctions following BRI 24h after reperfusion through increase in BDNF protein expression.

The search for psychoactive plants possessing therapeutic potential in the treatment of anxiety and depression has attracted growing interest. One such plant, Nymphaea lotus (commonly known as water lily), is used in traditional medicine for analgesic and sedative effects. The present study sought to assess the anti-anxiety and antidepressant activities of crude leaf extract of N. lotus and determine possible mechanisms of action.
Material and Barbiturate sleep induction, rota-rod, light/dark box , elevated plus maze, forced swimming test (FST) and open field test (OFT) were conducted. Male Albino Swiss mice were treated orally with vehicle 10 mL/kg, imipramine 15 mg/kg (reference drug in the FST), diazepam 1 or 5 mg/kg (reference drug in the OFT) or N. lotus extract (CEN) 20, 60 or 180 mg/kg. Mice were pretreated with p-chlorophenylalanine methyl ester (PCPA) 100 mg/kg, 𝛼-methyl-p-tyrosine (AMPT) 100 mg/kg, prazosin (PRAZ) 0.5 mg/kg or yohimbine (YOH) 1 mg/kg prior to oral administration of vehicle 10 mL/kg or CEN 20 mg/kg to determine potential mechanisms of action. Monoamine oxidase (MAO) assay and quantification of brain derived neurotrophic factor (BDNF) were performed.
CEN potentiated sodium pentobarbital-induced hypnotic effect and anxiolytic-like effect without altering immobility time in FST. Both MAO activity and BDNF level remained unchanged.
These results suggest anxiolytic-like effect of CEN and involvement of noradrenergic mechanism due to the blockade of anxiolytic-like effect by AMPT and PRAZ.

Aims: The biosynthesis of nanoparticles is widely considered today. The aim of this investigation was the biosynthesis and coating of Ag.NPs with Zataria multiflora (Zm-Ag.NPs) leaf extract and assess its apoptosis promoting effects.
The Zm-Ag.NPs was characterized by UV-visible and FTIR spectroscopy, TEM, EDS, DLS and measurement of zeta-potential. Apoptosis induction effects of Zm-Ag.NPs were assessed using acridine orange – propidium iodide (AO/PI) and DAPI staining, caspase3/9 activation assay and annexinV/PI assay. We also assess changing on P53, matrix metalloproteinases 2 (MMPs) and vascular endothelial growth factor A (VEGF-A) genes expression with semi-quantitative RT-PCR.
The UV-visible spectroscopy results showed that the surface plasmon resonance band (SRP) for Zm-Ag.NPs was around 440 nm also FTIR spectroscopy indicated plant material embedded around of Zm-Ag.NPs. The TEM images of the samples revealed that the Ag.NPs varied in morphology also presence of the silver element was monitories with EDS. the mean size of Zm-Ag.NPs were 30 nm. The Zm-Ag.NPs decrease cell viability in a dose and time dependent manner (IC50 = 15 μg/ml). AO/PI and DAPI staining indicated chromatin fragmentation also annexinV externalization assay using flow cytometer confirm promoting programmed cell death in treated cells. Apoptosis induced through caspase 3/ 9 activation pathway. This promoting apoptosis effects didn’t relate with P53 gene up regulation. Finally, it was found that Zm-Ag.NPs inhibited cancer cell metastasis through a decrease in MMP and VEGFA expression.
Zm-Ag.NPs acts as carrier for plant material compound that can apply as anticancer agents.

Marine Soft corals have frequently been studied in recent years because of their specific chemical compounds in tissue engineering and regenerative medicine. The aim of this study was to investigate anti-cancer property of extracted compound from Virgularia gustaviana and their effect on inducing of apoptosis. The extraction process was carried out with ethyl acetate for 5 days and the extract was separated by silica-gel column chromatography. The column was washed with n-hexane-ethyl acetate solvent at ratio of 10:0 to 0:10. Thin layer chromatography (TLC), High performance thin layer chromatography (HPTLC), high performance liquid chromatography (HPLC), and 13C NMR spectroscopy were used for qualitative identification of compounds. The viability of HeLa and MDA-MB-231 cancer cells was investigated using MTT assay at the concentrations of 25, 50, and 100 µL/mL of extracted compounds. Immunocytochemistry and Western Blot analyses were used to evaluate expression of apoptotic markers caspase-3 and caspase-8 in cancer cells after treating with effective fractions (based on viability of cancer cells) and the results were compared with Sarcophine. From ten isolated fractions (A-J), Retention time and Retention Factors (Rf) of fractions G, I, and J were the same as Sarcophine. Fraction G, I, and J dose-dependently decreased cancer cell viability compared to control group and Sarcophine. Treatment of cancer cells with the latest fraction increased expression of caspase-3 and caspase-8 demonstrating induction of apoptosis as possible mechanism of action. According to the results, the compounds extracted from Virgularia gustaviana inhibit the growth of cancer cells by inducing of apoptosis pathway; an effect which needs to be further investigated in the future studies.

Wedelolactone is known to have biological activities such as anti-inflammation hepatitis, anti-hepatotoxic activity, and trypsin inhibitory effect. However, up to date, there has not been studied deeply in the role of wedelolactone for zymosan-induced signaling pathways in the process of regulating the excessive inflammatory responses in host. Here, we demonstrated that wedelolactone plays an essential role for regulation of zymosan-induced inflammatory responses in murine bone marrow-derived macrophages (BMDMs). The zymosan-mediated secretion of tumor necrosis factor-α (TNF)-α), interleukin (IL)-6), and IL12p40 but not IL-10 in BMDMs was significantly inhibited by pre-treatment with wedelolactone (30 µg/ml, P

Acanthamoeba keratitis (AK) is a sight-threatening infection of the cornea disease that often presents with a lengthy and not fully effective treatment. Current therapeutic options against Acanthamoeba are not very effective against the cyst. Calibrated trophozoite/cyst suspension was incubated with the same volume of serial dilutions of the Trigonella foenum graecum aqueous extract (200, 250, 350, 450, 600, and 750 mg/mL) in microcentrifuge tubes and mixed by pipetting up and down. After that, the tubes were incubated at 26 ºC for 24, 48 and 72 h. The obtained result revealed that incubation of the extract (at concentrations ranging from 200 to 750 mg/mL) with Acanthamoeba was able to decrease the number of viable trophozoites and cysts. In the presence of up to 450 mg/ml non-viable trophozoites were observed whereas cysts were only eliminated when incubated with 750 mg/ml of the extract. Furthermore, no cytotoxicity of the extract even at the highest concentration tested in the study showed to be toxic for corneal cells. Further researches are needed to determine the exact active compounds involved in the anti-Acanthamoeba activities of Trigonella foenum graecum. To this end, T. foenum graecum could be a promising agent in the development of novel therapeutic substances against Acanthamoeba.

Scrophularia genus belonging to the family of Scrophulariaceae, is a medicinal plant widely distributed in Iran. In the present study,the anti-malarial activity of different extracts of three Iranian endemic species of Scrophularia including S. frigida, S. subaphylla and S. atropatana, was screened by an in-vitro preliminary assay.
The plant materials were extracted successively with n-hexane, dichloromethane (DCM), and methanol (MeOH) at room temperature by soxhlet extractor. In order to assess anti-malarial activity of obtained extracts, cell free β-hematin formation assay was applied.
Amongst the extracts, DCM extract of S. frigida exhibited remarkable anti-malarial activity with IC50 value of 0.67 ± 0.11 mg/mL. In contrast, MeOH and n-hexane extracts of all plants illustrated insignificant or moderate activity in this assay. Furthermore, preliminary phytochemical analysis along with TLC and GC-MS analysis of potent extract (DCM extract of S. frigida) were performed for more clarification. These methods revealed that the notable anti-malarial activity might be due to the presence of active constituents like methoxylated flavonoids, methylated coumarins, and diterpenoids.
From the nine extracts of different species of Scrophularia, DCM extract of S. frigida showed potent inhibitory activity on β-hematin formation assay. Hence, it seems that it is noteworthy to concentrate on purifying the active chemical constituents of DCM extract and determining the pure anti-malarial components.

In this study, the antioxidant, antiacetylcholinesterase, anti-inflammatory, and DNA protecting activities of the aerial parts of Glaucium grandiflorum var. grandiflorum were evaluated. It was found that the lyophilized methanolic extract exhibited an inhibitory capacity against FeCl3/ascorbic acid induced posphatidylcholine liposome oxidation (EC50 = 2.62  0.08 mg/mL), quenched HOCl (5.87  0.07 mg/mL ), stable DPPH (EC50 = 2.03  0.17 mg/mL) and ABTS cation radicals (EC50 = 4.80  0.14 mg/mL) and acted as reductant as expressed by the FRAP value (2.453  0.07 mM/L Fe2). The acethylcholinesterase inhibition capacity of the lyophilized methanolic extract at 320 μg/mL (80.75  1.59%) was found to be strong and almost equal to the inhibition capacity of the positive control, galantamine (82.23  2.21%) at 25 μg/mL. The significant AChE inhibitory activity suggests that the extract may be beneficial in the treatment of Alzheimer’s disease. The extract also showed inhibitory activity against plasmid DNA damage (94 %), as well as COX-2 (69.05 %), which is a target for many anti-inflammatory and cancer-preventive drugs. These results indicate that G. grandiflorum var. grandiflorum methanolic extract is an excellent source of compounds with antioxidant, anti-cholinesterase and anti-inflammatory properties that prevent DNA damage.

Scrophularia umbrosa is a medicinal plant used as a traditional herb. This study was designed to investigate the phytochemical analysis of methanol (MeOH), DCM, and n-Hexane extracts of rhizome as well as total phenol and total flavonoid contents (TPC and TFC). In-vitro β-hematin formation assay and DPPH method were applied for analyzing antimalarial and free-radical scavenging activities of the extracts, respectively. The formation of hemozoin has been proposed as an ideal drug target for antimalarial screening programs. The results showed that n-hexane and MeOH extracts of rhizome had no significant inhibitory effect on heme biocrystallization whereas the DCM extract of rhizome showed moderate antimalarial activity in comparison with chloroquine. GC-MS data showed that volatile portions of DCM and n-Hexane extracts from S. umbrosa contained a few identifiable compounds. Moreover, fractions 20% and 40% MeOH-Water of MeOH extract of S. umbrosa displayed moderate to strong free radical scavenging activity which showed a positive relation between phenolic and flavonoid contents and free radical scavenging activity. Based on the results, the fractions of MeOH extract were evaluated by 1HNMR for predicting the groups of natural compounds and interfacing of chemical and biological assessments.

Cadmium (Cd) is a highly toxic heavy metal, wide occupational and an environmental pollutant, affecting human health. Probiotics especially lactic acid bacteria (LAB) have the capacity to bind, remove and to decrease tissue cadmium levels. The objective was to evaluate the potency of Cd binding capacity, antioxidative properties of probiotic bacteria against cadmium in vitro and its probable detoxification effect against Cd-induced toxicity in mice. To asses this objective, resistance against cadmium and antioxidative properties (via DPPH radical scavenging and inhibition of lipid peroxidation) were estimated for thirteen probiotic bacteria. Streptococcus thermophilus was selected among investigated bacteria as it had the highest MIC against cadmium and remarkable antioxidant activities for treatment of Cd toxicity in Swiss albino mice by preventive and therapeutic protocols. Blood cadmium levels, reduced glutathione (GSH), malondialdehyde (MDA) and histopathological changes in the liver of mice were estimated at 6, 24 and 48 h post to acute Cd exposure (oral dose with 50 mg/kg body weight). On exposure to Cd a significant increase in blood Cd, MDA and reducing in GSH levels were observed. S. thermophilus offered a significant protective effect against Cd toxicity by decreasing the cadmium levels in blood and attenuation alterations in the levels of GSH and MDA and improved hepatic histopathological changes caused by Cd toxicity. These results indicated the protective action of S. thermophilus against acute cadmium toxicity as well as their beneficial health effects and suggested its use as a safe and efficacious nutritional dietary supplement to reduce cadmium toxicity.

In the present study, the physicochemical properties and antioxidant activities of different Iranian honey samples are investigated using various multivariate techniques in order to develop a quality control model. Forty-eight Iranian honey samples were tested for 15 physicochemical and antioxidant parameters. The parameters for which the samples were tested included color intensity, moisture, electrical conductivity, pH, free acidity, diastase activity, hydroxymethylfurfural content, proline level, total phenolic content, antioxidant activity, and radical scavenging activity. The study attempted to differentiate honey samples based on origin and composition. In the study, the Iranian honey samples were classified according to their respective physiochemical properties and antioxidant activities using principal component analysis and hierarchical cluster analysis. Furthermore, the relationships between the geographical and botanical origins were determined for the samples used in the study.

Glycyrrhiza uralensis Fisch. (G. uralensis) is one of the most widely used herbal medicines for the treatment of cough, spasms, pain, inflammation and low immunity This study was designed to enrich total flavonoids (TFF) from G. uralensis and investigate the anti-inflammatory activity of TFF. The anti-inflammatory activity was evaluated by inflammatory models of dimethylbenzene (DMB)-induced ear vasodilatation in mice and carrageenan-induced paw edema in rats. The chemical profiling of TFF was identified by HPLC and colorimetric assay. The TFF mainly contained liquiritin apioside, liquiritin, isoliquiritin apioside, liquiritigenin and isoliquiritigenin without glycyrrhizic acid. Treatment with TFF showed significant anti-inflammatory activities at two models. In the rat paws with carrageenan, TFF at the dose of 500 mg/kg significantly inhibited the edema formation at 1 to 5 h compared to control group. But TFF at dose of 250 and 125 mg/kg only significantly decreased the edema at 2 to 5 h. Application of TFF (500 and 250 mg/kg) significantly reduced the expression of IL-1β and iNOS. TFF at all doses noticeably declined levels of NO and MDA into the site of inflammation, while only i. g. TFF at a dose of 500 mg/kg significantly decreased TNF-α levels in the carrageenan-injected paws. In addition, the increase of SOD level was showed by TFF at all doses. Our results revealed that TFF exhibited significant anti-inflammatory activity in acute inflammatory models. The activity maybe mainly contributed by liquiritin apioside, liquiritin, isoliquiritin apioside, liquiritigenin and isoliquiritigenin.

Epilepsy is a chronic neurological disease which disrupts the neuronal electrical activity. One-third of patients are resistant to treatment with available antiepileptic agents. The use of herbal medicine for treating several diseases including epilepsy is on the rise. Therefore, further investigation is required to verify the safety and effectiveness of Phytomedicine in treating diseases. The current study is an attempt to elucidate the electrophysiological mechanism of the effect of Dorema ammoniacum gumon a cellular model of epilepsy, using intracellular recording method. The gum was applied either after or before pentylenetetrazole, as an epileptic drug, in order to explore the possible therapeutic and preventive effects of gum. Treatment with D. ammoniacum gum alone increased the neuronal excitability and when applied before or after treatment with PTZ not only did not prevent or change the electrophysiological changes induced by PTZ but also re-enhanced the induction of hyperexcitability and epileptiform activity through depolarizing membrane potential, increasing the firing frequency and decreasing the AHP amplitude. However, phenobarbital, as a standard anti-epileptic agent, almost reversed the effect of PTZ and preserved the normal firing properties of F1 neurons.
The possible candidate mechanism of the effect of gum on neuronal excitability could be suppressive effects of gum on voltage and/or Ca2 dependent K channels currents underlying AHP.

Tumor necrosis factor alpha (TNF-α) expression amplifies to excess amounts in several disorders such as rheumatoid arthritis and psoriasis. Although, Anti-TNF biologics have revolutionized the treatment of these autoimmune diseases, formation of anti-drug antibodies (ADA) has dramatically affected their use. The next generation antibodies (e.g. Fab, scFv) have not only reduced resulted immunogenicity, but also proved several benefits including better tumor penetration and more rapid blood clearance. Using affinity selection procedures in this study, a scFv antibody clone was isolated from naïve Tomlinson I phage display library that specifically recognizes and binds to TNF-α. The TNF-α recombinant protein was expressed in genetically engineered Escherichia coli SHuffle® T7 Express, for the first time, which is able to express disulfide-bonded recombinant proteins into their correctly folded states. ELISA-based affinity characterization results indicated that the isolated novel 29.2 kDa scFv binds TNF-α with suitable affinity. In-silico homology modeling study using ‘ModWeb’ as well as molecular docking study using Hex program confirmed the scFv and TNF-α interactions with a scFv-TNF- α binding energy of around -593 kj/mol which is well in agreement with our ELSIA results. The cloned scFv antibody may be potentially useful for research and therapeutic applications in the future.

Microencapsulation with hydrocolloids as a modern technique has been used to prolong the survival of probiotics during exposure to harsh conditions. In this study, alginate-Hylon starch microcapsules with genipin cross-linked chitosan and poly-L-lysine coatings were developed to encapsulate four strains of probiotic bacteria, including Lactobacillus casei (ATCC 39392), Bifidobacterium bifidum (ATCC 29521), Lactobacillus rhamnosus (ATCC 7469), and Bifidobacterium adolescentis (ATCC 15703). The viability of probiotics was investigated under heat treatment (72, 85, and 90 °C, 0.5 min), simulated gastric juice (along with pepsin, pH = 2, 2 h at 37 C), and simulated intestinal juice (along with pancreatin and bile salts, pH = 8 2 h at 37 C). The morphology and size of microcapsules were measured by scanning electron and optical microscopy. Results of this research demonstrated that, compared with the free form, microencapsulated probiotics had significantly (P

The stereoselective pharmacokinetic of Tramadol (T) and its main metabolites concerning the influence of CYP2D6 phenotype and gender on the phase I metabolism of this compound was studied after administration of 100 mg single oral dose of racemic T to 24 male and female subjects. The pharmacokinetic parameters were estimated from plasma concentrations of the analytes enantiomers. The metabolic ratioof T enantiomers was used for CYP2D6 phenotype determination. The plasma concentrations of both tramadol enantiomers were considerably higher in Poor metabolizers (PM) than in extensive metabolizers (EM), resulting in 43% and 37% increase in AUC values of ()-T and (-)-T respectively. The plasma concentrations of the ()- and (-)-M1 enantiomers in EMs were significantly higher than the respective concentrations in PMs. The N-demethylation pathway was indirectly affected by CYP2D6 phenotypic differences. The plasma concentration of both enantiomers of M2 in PMs was higher than Ems. Although the concentration profiles and most of the calculated pharmacokinetic parameters of T and its main metabolites appears to be different in EMs and PMs, only the stereoselectivity of M1 enantiomers was significantly different in relation to CYP2D6 subgroups. No significant gender-related difference in the pharmacokinetics of T and its metabolites was observed.

Patients suffering from headache, particularly migraine type, are among the most dissatisfied patients. The aim of this study was comparing the efficacy of pregabalin with valproate sodium, in preventing migraine headache.
In a randomized, double-blinded study, adult patients eligible for prophylactic treatment (i.e., patients with 4-15 attacks per month in last two months) were recruited. Patients’ demographic data, duration of symptoms, headache frequency (attacks per month) and intensity (based on visual analogue scale) and also drugs used to relief headache were recorded. The patients were randomly assigned to two groups; valproate sodium (200 mg two times daily) and pregabalin (50 mg two times daily). The patients were examined by neurology specialist monthly for three months and the related data were recorded. The Data were analyzed using SPSS version 21, with related statistical tests.
Total number of 140 patients with recurrent migraine were entered into the study. Sixty-nine patients were assigned to group A and 71 to group B by the randomizing table. Inter-group analysis of data in two arms of the study showed that two medications were equally effective except that pregabalin was not significantly effective in reducing number of attacks during first month of therapy compared to baseline. This differences were not significant at second and third month of the study.
Our study showed that pregabalin, has comparable efficacy with valproate sodium in reducing migraine frequency, intensity, and duration of attacks and could be an alternative for migraine prophylaxis.

The response to glucocorticoids (GCs) therapy classifies severe refractory asthma (SRA) and mild asthma, so the glucocorticoid receptors (GCRs) gene expression may be involved in SRA pathogenesis. Thus, it is aimed to compare the expression levels of two GCR isoforms (GCRα and GCRβ) in SRA, mild asthmatics, and healthy controls. Total RNA was isolated from the peripheral blood mononuclear lymphocytes of 13 SRA patients, 14 mild asthma patients and 30 healthy volunteers. The expression levels of GCR isoforms were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).
The expression level of GCR isoforms did not show any significant difference between the cases/control groups. However, the relative expression analysis between asthma/control, SRA/control and SRA/asthma groups was in the order of 0.933, 0.768 and 0.823 for GCRα and 0.697, 1.014 and 1.454 for GCRβ, respectively. Also, the expression fold change of GCRα/GCRβ in asthma, SRA and control groups was 786.88, 445.72 and 588.13, respectively. The GCRα and GCRβ isoforms did not show any correlation in SRA; but they had significant correlation in both healthy volunteers (r = 0.490, P = 0.007) and mild asthmatics (r = 0.786, P = 0.001). Also, the GCRα expression level had significant inverse correlation with age in SRA (r = -0.709, P = 0.007).
Glucocorticoid receptors are related to, but not directly responsible for GC resistance. Since the GCRα/GCRβ expression ratio decreased in SRA, studies are needed to assess its value in diagnosing GC resistance.

Burden of Chronic Obstructive Pulmonary Disease (COPD) is substantial and increasing in the world. There are controversial reports regarding vitamin D supplementation in COPD. We investigated relationship between vitamin D3 (Cholecalciferol) supplementation with Health Related Quality of Life (HRQOL) and symptom recovery in AECOPD patients with concurrent Vitamin D Deficiency (VDD). A placebo-controlled randomized clinical trial was designed. AECOPD patients with VDD were randomly allocated to receive either vitamin D 300,000 IU (n = 35) or placebo (n = 35) by intramuscular injection. Primary outcomes included the HRQOL assessed by St. George's Respiratory Questionnaire (SGRQ), and the symptom recovery evaluated by the modified Medical Research Council (mMRC) Dyspnea scale, determined at baseline and at days 30 and 120 post-intervention. Secondary endpoints were length of hospital stay (LOS), rehospitalization and mortality rates.
Sixty-two patients, 30 patients in the vitamin D and 32 patients in the placebo groups, with mean ± SD age of 63.42 ± 8.48 years accomplished the study. Baseline vitamin D levels in the vitamin D and placebo groups were 10.59 ± 3.39 and 11.12 ± 3.17 ng/mL, respectively. These levels reached 36.85 ± 11.80 and 12.30 ± 3.66 in the vitamin D and placebo groups, respectively, at day 120 (p

Adverse drug events (ADEs) may cause serious injuries including death. Spontaneous reporting of ADEs plays a great role in detection and prevention of them, however, underreporting always exists. Although several interventions have been utilized to solve this problem, they are mainly based on experience and the rationale for choosing them has no theoretical base. The vast variety of behavioral theories makes it difficult to choose appropriate theory. Theoretical domains framework (TDF) is suggested as a solution. The objective of this study was to select the best theory for evaluating ADE reporting in hospitals based on TDF. We carried out three focus group discussions with hospital pharmacists and nurses, based on TDF questions. The analysis was performed through five steps including coding discussions transcript, extracting beliefs, selecting relevant domains, matching related constructs to the extracted beliefs and determining the appropriate theories in each domain. The theory with the highest number of matched domains and constructs was selected as the theory of choice. A total of six domains were identified relevant to ADE reporting, including “Knowledge”, “Skills”, “Beliefs about consequences”, “Motivation and goals”, “Environmental context and resources” and “Social influences”. We found theory of planned behavior as the comprehensive theory to study factors influencing ADE reporting in hospitals, since it was relevant theory in five out of six relevant domains and the common theory in 55 out of 75 identified beliefs. In conclusion, we suggest theory of planned behavior for further studies on designing appropriate interventions to increase ADE reporting in hospitals.

Among non-oil exports and in trade arena, drug has always been strategic importance and most government especially industrialized countries pay special attention to its production and trade issues. Thus, having a comprehensive view from economic perspective to this section is essential for suggesting intervention. This was a descriptive-analytical and panel study. In this study, gravity model is used to estimate Iran’s bilateral intra-industry trade in pharmaceutical products in the 2001-2012 periods. To illustrate the extent of pharmaceutical’s intra-industry trade between Iran and its major trading partners, the explanatory variables of market size, income, factor endowments, distance, cultural contributions and similarities and special trade arrangements have been applied. Analysis of factors affecting Iran’s bilateral intra-industry trade in pharmaceutical industry showed that the average GDP and cultural similarities had a significant positive impact on Iran’s bilateral IIT, while the difference in GDP has a negative and significant effect. Coefficients obtained for the geographical distance and the average ratio of total capital to the labor force is not consistent with theoretical expectations. Special trade arrangements did not have significant impact on the extent of bilateral intra-industry trade between Iran and its trading partners. The knowledge of the intra-industry trade between Iran and its trade partners make integration between the countries. Factors affecting this type of trade pattern underlie its development in trade relationship. Therefore, the findings of this study would be useful in helping to develop and implement policies for the expansion of the pharmaceutical trade.