Advanced Pharmaceutical Bulletin
Volume:8 Issue: 1, Mar 2018

To stress the influence of Coenzyme Q10 (CoQ10) on the structural properties of liposomes as model membranes and to investigate the possible role of CoQ10 or CoQ10 doped in liposomes when topically instilled as eye drops, in preventing cataract.
The molecular interaction between liposomes and Coenzyme Q10 was examined using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Rat pups were randomly divided into six groups comprising 15 pups. Group (1), control group. Group (2), untreated model of cataract, received a single subcutaneous injection of sodium selenite. Instillation of pure CoQ10 (Group 3), CoQ10 encapsulated into neutral (Group 4), positive (Group 5) and negative (Group 6) Dipalmitoyl phosphatidylcholine (DPPC) liposomes on the opacification of lenses in rat pups after sodium selenite injection was topically received.
The incorporated CoQ10 is probably associated with lipid bilayers where it interacts to a large extent and perturbs them. This results in strong broadening and shift to lower temperature (94°C) of the major characteristic endothermic peak of pure DPPC at 105°C. FTIR showed that the incorporation of CoQ10 into DPPC induces a conformational change in the polar region of DPPC. Ophthalmological and Biochemical studies revealed that CoQ10 alone followed by negatively charged liposomes doped with CoQ10 are more effective in reducing the progress of cataract as well as improving the lens soluble proteins levels and total antioxidant capacity.
The interactions of CoQ10 with membrane systems may contribute to a better understanding of CoQ10 physiological properties and the development of therapeutically advanced systems.

Cartilage regeneration by using polymeric scaffolds is a new option for treatment of osteoarthritis. A good scaffold for tissue engineering should copy the characteristics of natural extracellular matrix. The purpose of this study was to make a dosage form with proper reliability and stability for cartilage repair.
Hybrid scaffolds containing different ratios of hyaluronic acid (HA) and collagen were prepared and loaded with prednisolone as anti-inflammatory agent. Two different dosage forms (lyophilized implantable disk and thermo-sensitive gels) were examined. A scaffold of cross-linked HA was used as control. Different characterization tests were considered including differential scanning calorimetry (DSC), scanning electron microscopy, mechanical evaluations, and drug release.
The physical and chemical performance of hybrid-scaffolds was better than HA scaffold. Increasing the concentration of HA and collagen improved the physical and chemical characteristics. Regarding the mechanical properties of the hybrid scaffold, the pore size was 20-200µm, compressive modulus was 54.77±0.31 kPa, more than 1200% water uptake was observed after 4 days, gelation temperature was 32±0.16°C, gelation time was 2.4±0.1 min, and drug release was controlled for 5 days by Higuchi release kinetic model.
It seems that this porous hybrid scaffold could be a suitable choice in cartilage regeneration as well as a controlled-release system for delivery of prednisolone in osteoarthritis.

The poor bioavailability of drugs in the ocular delivery systems is an important issue and development of delivery systems with prolonged release profile could be in a major importance. This study aims to develop an ocular delivery system using electrospun nanofibers to be a candidate insert for delivery of triamcinolone acetonide.
For this purpose, three different chitosan-based formulations were prepared by electrospinning method, and electrospun nanofibers were compared to a formulation comprising hydrophobic polymers (Eudragit S100 and Zein). The electrospun nanofibers were characterized by SEM and FTIR analyses. The release profile and release kinetic models of all the formulations were also examined.
The SEM photographs of electrospun nanofibers revealed that among the four designed formulations, formulation obtained by electrospinning of chitosan and PVP possessed the best quality and the minimum size (120 ±30 nm) , which resulted the most uniform and bead-free nanofibers. This formulation also possessed the prolonged release profile of triamcinolone acetonide and was the only electrospun nanofiber following the zero-order kinetic profile. Due to the small diameter and uniformity of this formulation, the prolonged and well controlled release profile, it could be taken into account as a candidate to overcome the drawbacks of the commonly used ocular delivery systems and be used as ocular insert.
This study confirmed the ability of electrospun nanofibers to be used as ocular inserts for delivery of ophthalmic drugs.

Cardiovascular gene therapy is a sophisticated approach, thanks to the safety of vectors, stable transgene expression, delivery method, and different layers of the heart. To date, numerous expression vectors have been introduced in biotechnology and biopharmacy industries in relation to genetic manipulation. Despite the rapid growth of these modalities, they must be intelligently designed, addressing the cardiac-specific transgene expression and less side effects. Herein, we conducted a pilot project aiming to design a cardiac-specific hypoxia-inducible expression cassette.
We explored a new approach to design an expression cassette containing cardiac specific enhancer, hypoxia response elements (HRE), cardiac specific promoter, internal ribosome entry site (IRES), and beta globin poly A sequence to elicit specific and inducible expression of the gene of interest. Enhanced green fluorescent protein (eGFP) was sub-cloned by BglII and NotI into the cassette. The specificity and inducible expression of the cassette was determined in both mouse myoblast C2C12 and mammary glandular tumor 4T1 as ‘twin’ cells. eGFP expression was evaluated by immunofluorescence microscope and flow cytometry at 520 nm emission peak.
Our data revealed that the designed expression cassette provided tissue specific and hypoxia inducible (O2 It is suggested that cardiac-specific enhancer combined with cardiac-specific promoter are efficient for myoblast specific gene expression. As well, this is for the first time that HRE are derived from three well known hypoxia-regulated promoters. Therefore, there is no longer need to overlap PCR process for one repeated sequence just in one promoter.

The worldwide prevalence of metabolic disorders such as diabetes is increasing rapidly. Currently, the complications of diabetes are the major health concern. The aim of this study was to investigate the effect of high performance (HP) inulin supplementation on glucose homeostasis via KLF5 mRNA expression in adults with type 2 diabetes.
In the present clinical trial conducted for a duration of 6 weeks, 46 volunteers diabetic patients referring to diabetes clinic in Tabriz, Iran, were randomly assigned into intervention (n= 23, consuming 10 gr/ d HP inulin) and control groups (n= 23, consuming 10 gr/ d starch). We assessed glycemic and anthropometric indices, blood lipids and plasmatic level of miR-375 as well as KLF5 mRNA expression before and after the intervention.
Findings indicated that inulin supplementation significantly decreased fasting plasma glucose (FPG) in comparison to the placebo group (P Considering the improvements of FPG level in diabetic patients, it seems that HP inulin supplementation may be beneficial in controlling diabetes via the expression of some genes. However, further studies are needed to achieve concise conclusions.

Plasmonic photo thermal therapy (PPTT) is a therapeutic method in which the photon energy is rapidly transformed into heat via a series of radiative and non-radiative phenomena to ablate cancer. Plasmonic NPs, such as silver NPs (Ag NPs), have considerable properties in optical absorbance. Furthermore, good thermal conductivity and cell penetration ability of carbon nanotubes (CNTs) could improve the efficacy of Ag NPs for PPTT. Decoration of the multi-walled carbon nanotubes (MWCNTs) with silver has been developed to enhance thermal conductivity of the MWCNT particles.
The Ag NPs were decorated on the CNTs and the ability of these particles (CNT/Ag NPs) in reduction of melanoma tumor size after PTT was evaluated experimentally. For comparison, the PTT of silver nanorods (Ag NRs) and CNTs were investigated. The melanoma tumor was induced by injection of B16/F10 cell line to the inbred mice. Different NPs were injected into the tumors and then irradiated via laser diode (λ=670 nm, P=500 mW, and I= 3.5 W/cm2) at scheduled time.
Monitoring of tumor sizes showed that integration of CNTs with silver could enhance the optical absorption of CNTs and improve tumor destruction in PPTT technique.
The CNT/Ag NPs could act as a potent agent in PPTT method in curing solid tumors.

In the present study, postconditioning effect of fructose against ischemia/reperfusion (I/R)-induced arrhythmias and infarct size were investigated in isolated rat heart.
The isolated hearts were divided into 7 groups, mounted on a Langendorff apparatus at constant pressure then subjected to 30 min zero flow global ischemia followed by 120 min reperfusion. In the control group, normal Krebs–Henseleit (K/H) solution was perfused into the hearts throughout the experiment. In two separate sets of experiments, the treatment groups received 12, 24 and 48 mM of fructose with/without normal glucose in K/H solution for 20 min at the beginning of reperfusion. Cardiac arrhythmias including number of ventricular tachycardia (VT), total ventricular ectopic beats, incidence and duration of VT, reversible and irreversible ventricular fibrillation were recorded and analyzed during the first 30 min of reperfusion. Computerized planimetry method was used to determine volume and percentage of infarct size.
Administration of fructose as a postconditioning agent clearly reduced volume and percentage of infarct size in the all treatment groups. The effect was statistically significant especially in the hearts that treated by fructose plus glucose (P The results showed that perfusion of high concentration of fructose alone or coincident with glucose in globally ischemic-reperfused isolated rat hearts can reduce infarct size without inhibitory effect against reperfusion arrhythmias. Probably, fructose by providing adequate ATP for cardiac functions may inhibit necrosis and death of cardiomyocytes during I/R.

Human hepatocellular carcinoma is one of the most common causes of death in the world. Metformin and rapamycin may decrease the expression of VEGF protein and subsequently angiogenesis. The purpose of this study was to evaluate the effect of these two drugs on expression of VEGF protein and the cell proliferation in the hepatocellular carcinoma cell line (ATCC HB-8065).
HepG2 was cultured in RPMI-1640 medium at 37°C for 48h as a pre-culture and then treated by different concentrations of metformin (0, 5, 10 and 20 mM) and rapamycin (0, 5, 10 and 20 nM) at different times (12, 24 and 48 h). Cell viability was assessed by the MTT assay. Total RNA was extracted by the Trizol reagent and VEGF gene expression was analyzed by quantitative real-time PCR and was calculated by 2–ΔCt method. The VEGF protein level was determined by Elisa assay. Finally, Apoptosis index was calculated by DAPI staining.
Metformin and rapamycin significantly decrease cancer cells viability (p Metformin and rapamycin have an anti-tumor effect on HCC. According to our data rapamycin might have an anti-angiogenesis effect via inhibition of VEGF expression. Our results provide an insight into future clinical strategies to improve chemotherapy outcomes in HCC.

Onopordon acanthium L. is known for its medicinal properties. Our recent study showed that its seed extract is a novel natura angiotensin-converting-enzyme inhibitor (ACEI). This study was carried out to investigate its possible antihypertensive effects in patients receiving losartan.
This uncontrolled clinical trial was carried out among 20 patients (30-60y) with uncontrolled hypertension despite receiving 50 mg losartan (stage I & II) in two hospitals in Iran. After completing informed consent, patients were treated by 2 capsules [each 1g of Onopordon acanthium seed extract (OSE)] as add-on therapy, two times per day.
18 patients completed the study (50.94 ±8.37y). Mean systolic blood pressure (SBP) at the baseline was 151.9 ± 13.74mmHg and at the end of the study, it was 134.6 ± 18.25 mmHg and mean diastolic blood pressure (DBP) was 97.41 ± 10.36 at the baseline and was 85.71 ± 7.481 after 8 weeks. OSE significantly reduced SBP and DBP at the end of 8 weeks (P=0.003, 95% CI: -19.7, -15.1; P=0.0006, 95% CI: -10.23, -13.15; respectively). No evidence of hepatic or renal toxicity was detected.
Based on the results of this study OSE has antihypertensive property with no significant adverse effects. However, because of the low number of samples, this medication may be not safely administered. The results of this study could be the basis for further studies with larger sample size. IRCT registration number: IRCT2013020712391N.

The size of polymeric nanoparticles is considered as an effective factor in cancer therapy due to enterance into tumor tissue via the EPR effect. The purpose of this work was to investigate the effective parameters on poly(lactic-co-glycolic acid)-paclitaxel (PLGA –PTX) nanoparticles size.
We prepared PLGA-PTX nanoparticles via single emulsion and precipitation methods with variable paremeters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration.
PLGA-PTX nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The results exhibited that the diameter of nanoparticles enhanced with increasing drug, polymer and PVA concentrations whereas organic to aqueous phase volume ratio and sonication time required to the optimization for a given size.
The precipitation method provides smaller nanoparticles compared to emulsion one. Variable parameters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration affect diameter of nanoparticles.

Biofilm growth exerts a negative impact on industry and health, necessitating the development of strategies to control. The objective of this work was study the lytic activity of the phage isolated from the sewage network in the formation and degradation of Escherichia coli biofilms.
E. coli cultures were incubated in 96-well polystyrene microplates under controlled conditions to evaluate the biofilm formation. The E. coli cultures and established biofilms were treated with the suspensions of the vB_EcoM-UFV017 (EcoM017) bacteriophage obtained from sewage for 24 hours. The E. coli bacterial density was measured using absorbance at 600 nm and the biofilms were measured by crystal violet staining. Polystyrene coupons were used as support for Scanning Electron Microscopy and Confocal Microscopy to evaluate biofilm formation.
The E. coli strains formed biofilms in polystyrene microplates after 48 hours’ incubation. The highest EcoM017 phage titer, in the prevention and degradation experiments, reduced the bacterial growth and the quantity of biofilm formed by E. coli in 90.0% and 87.5%, respectively. The minimum dose capable of reducing the biofilms of this bacterium was 101 PFU/mL after 24 hours. The preformed E. coli biofilm mass was reduced 79% post exposure to the phage in the degradation assay. Microscopic analysis confirmed the results obtained in the plates assays.
The EcoM017 phage prevented biofilm formation and degraded the E. coli-established ones. The EcoM017 phage isolated from sewage can reduce bacterial attachment and lyse the E. coli associated biofilm cells, offering biotechnological potential applicability for this phage.

Metformin is one of the most popular drugs tested against nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether calcium-vitamin D3 cosupplementation will intensify the effect of metformin on the prevention of high-fat, high-fructose (HFFr) diet-induced hepatic steatosis.
Male wistar rats (210±16 g) were assigned into the following seven groups: a Control group to receive a standard chow and six HFFr-fed groups to receive diets containing either normal (0.5% calcium and 1000 IU/kg vitamin D3) or high amount of calcium and vitamin D3 (2.4% calcium and 10000 IU/kg vitamin D3) (CaD), in combination with gastric gavage administration of either saline or 25 or 200 mg/kg body weight/day metformin. After 60 days, rats were assessed with respect to their anthropometric, metabolic and hepatic parameters, as well as their hepatic AMP-activated protein kinase (AMPK) phosphorylation.
Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation. In addition, slightly (and non-significantly) better effects of the combination in ameliorating steatosis and hepatic cholesterol content were observed.
Taken together, our results suggest that metformin and CaD could protect against the onset of HFFr diet-induced NAFLD in an insulin and AMPK-independent manner, without any marked additional benefits of their combination.

Nutritional quality and oxidation stability are two main factors in the evaluation of edible oils. Oils in their pure form do not have an ideal fatty acid composition or suitable oxidative stability during processing or storage.
This study was designed to evaluate the chemical, nutritional and rheological properties of oil mixtures in three ratios of olive: sesame: linseed, 65:30:5; 60:30:10 and 55:30:15. Acidity value, peroxide value, rancimat test, fatty acid profile, nutritional indexes and rheological properties of the oil blends were determined. The nutritional quality was determined by indexes, including the atherogenic and thrombogenic indexs; the ratios of hypocholesterolemic: hypercholesterolemic; poly unsaturated fatty acid: saturated fatty acid and the ω6:ω3.
The results indicated that blending of other vegetable oils with linseed oil could balance ω6:ω3. Results showed that formulated oils had a good balance of oxidation stability and nutritional properties as well. Rheological data showed that these oil blends followed Newtonian behavior at 4°C and 25°C.
According to the results, addition of linseed oil to vegetable oils containing high levels of bioactive compounds was a simple and economic practice to obtain a functional oil with good nutritional and stability properties.

The aim of the present study was to investigate the chemical properties of wild Tagetes minuta L. (family Astreacea) collected from Northern Iran during the flowering period concerning the chemical combination of the essential oil along with its antioxidant properties and composition of fatty acids.
The essential oil of the plant was extracted by a Clevenger approach and analyzed using gas chromatography-mass spectroscopy (Capillary HP-5ms GC/MS Column). Fatty acid contents of this species as a result of hexane extraction were analyzed by means of gas chromatography (GC-FID) while their phenolic contents were analyzed by high performance liquid chromatography (HPLC-UV). In this research also the total polyphenolic (TPC) and total flavonoid (TFC) content was determined spectrophotometrically while the antioxidant activity was evaluated using the DPPH (2,2'-diphenyl-1-picrylhydrazyl) bleaching method.
GC/MS analysis of the essential oil identified monoterpenoid fractions (52.13%) as the main components and among them dihydrotagetone (23.44%) and spathulenol (10.56%) were the predominant compounds. The evaluation of fatty acid content revealed that saturated acids were prevailing compounds and the major components are: palmitic (30.74±0.4%) and capric (24.15±0.5%) acids. Chromatographic separation of its phenolic contents indicated that this herb contain sinapic acid derivatives rather than hydroxybenzoic acid derivatives. Also the essential oil showed an effective antioxidant capacity (TPC=153.27±0.9 mg/g, TFC=63.79±0.1 mg/g, IC50 = 29.31±0.8 µg/ml).
The results proved that the plant could be used for nutritional and pharmaceutical purposes.

Adipose tissue is a highly active endocrine organ which plays a key role in energy homeostasis. The aim of this study was to determine the effects of dried licorice extract along with a calorie restricted diet on body composition, insulin resistance and adipokines in overweight and obese subjects.
Sixty-four overweight and obese volunteers (27 men, 37 women) were recruited into this double-blind, placebo-controlled, randomized, clinical trial. Participants were randomly allocated to the Licorice (n=32) or the placebo group (n=32), and each group received a low-calorie diet with either 1.5 g/day of Licorice extract or placebo for 8 weeks. Biochemical parameters, anthropometric indices, body composition and dietary intake were measured at baseline and at the end of the study.
A total of 58 subjects completed the trial. No side effects were observed following licorice supplementation. At the end of the study, waist circumference, fat mass, serum levels of vaspin, zinc-α2 glycoprotein, insulin and HOMA-IR were significantly decreased in the intervention group, but only the reduction in serum vaspin levels in the licorice group was significant when compared to the placebo group (p Supplementation with dried licorice extract plus a low-calorie diet can increase vaspin levels in obese subjects. However, the anti-obesity effects of the intervention were not stronger than a low-calorie diet alone in the management of obesity.

Angiogenesis plays an important role in numerous pathophysiological events like cancer. As a result of this, tranilast as an anti-fibrotic drug induces the promising antitumor activities through the inhibition of angiogenesis. Further, Teucrium polium (TP) is a herbal medicine (family Lamaceae) with antitumor properties. This study was conducted to investigate the combination effects of tranilast and T. polium on human umbilical vein endothelial cells (HUVECs) viability and apoptotic genes expression.
The HUVECs line was treated using different doses of tranilast and T. polium alone or their combination. The cell cytotoxicity was evaluated using MTT and LDH assays; apoptosis was examined using acridine orange/ethidium bromide staining, nitric oxide (NO) production was evaluated using Griess reaction and the expression of BAX and BCL-2 genes were detected using real-time RT-PCR. One-way analysis of variance (ANOVA) test was used to compare the data in different groups.
The survival rate of HUVECs was significantly reduced (p T. polium synergistically increased the antiangiogenic effect of tranilast on in vitro angiogenic model of HUVECs.

Diabetes mellitus is one of the major endocrine disorders, characterized by impaired insulin action and deficiency. Traditionally, Artocarpus heterophyllus stem bark has been reputably used in the management of diabetes mellitus and its complications. The present study evaluates the ameliorative activity of ethanol extract of Artocarpus heterophyllus stem bark in alloxan-induced diabetic rats.
Diabetes mellitus was induced by single intraperitoneal injection of 150 mg/kg body weight of alloxan and the animals were orally administered with 50, 100 and 150 mg/kg body weight ethanol extract of Artocarpus heterophyllus stem bark once daily for 21 days.
At the end of the intervention, diabetic control rats showed significant (p0.05) different with non-diabetic rats.
The results suggest that ethanol extract of Artocarpus heterophyllus stem bark may be useful in ameliorating complications associated with diabetes mellitus patients.

This paper introduces a green and simple hydrothermal synthesis to prepare carbon quantum dots (CQDs) from walnut oil with a high quantum yield. In addition, cytotoxic and apoptogenic properties of the CQDs were analyzed on human cancer cell lines.
The optical properties and morphological characteristic were investigated by the TEM, XRD, FT-IR, UV-vis and photoluminescence (PL).The cytotoxic potential of walnut CQDs was evaluated on PC3, MCF-7 and HT-29 human carcinoma cell lines using the MTT methods. The mechanism of action was studied by investigating the mode of cell death using the activation of caspase-3 and 9 as well as mitochondrial membrane potential (MMP). Cellular uptake of the CQDs was detected by fluorescence microscope. CQDs had an average size of 12 nm and a significant emission at 420 nm at an excitation wavelength of 350 nm was recorded.
The prepared CQDs possessed a good fluorescent quantum yield of 14.5% with quinine sulfate (quantum yield 54%) as a reference and excellent photo as well as pH stabilities. The walnut CQDs were proved to be an extremely potent cytotoxic agent, especially against MCF-7 and PC-3 cell lines. Induction of apoptosis by CQDs was accompanied by an increase in the activation of caspase-3. Caspase-9 activity did not increase after exposure to the CQDs. Additionally; the MMP did not show any significant loss.
The results of our study can corroborate the cytotoxic and apoptotic effect of walnut CQDs in the PC3 and MCF-7 cancer cell lines.

To determine and quantify vinblastine in different varieties of Catharanthus roseus using reversed-phase HPLC method.
The liquid chromatographic separation was performed using a reversed phase C18, Microsorb - MV column (250 mm x 4.6 mm, 5 µm) at room temperature and eluted with a mobile phase containing methanol – phosphate buffer (5 mM, pH 6.0) – acetonitrile with different proportion gradient elution at a flow rate of 2.0 mL min-1 and detection at 254 nm.
The HPLC method was utilized for the quantification of vinblastine in purple, red and white varieties of Catharanthus roseus leaves. The separation was achieved in less than 8 min. The peak confirmation was done based on the retention times and UV spectra of the reference substance. The method was validated with respect to linearity, precision, recovery, limit of detection and quantification. Results showed that the purple variety gives 1.2 and 1.5 times more vinblastine concentration compared to the white and pink varieties, respectively.
The obtained results from different varieties are thus useful for the purpose of vinblastine production from Catharanthus roseus plant.

Drug delivery has a critical role in the treatment of cancer, in particular, carbon nanotubes for their potential use in various biomedical devices and therapies. From many other materials which could be more biocompatible and biodegradable and which could form single-walled nanotubes, silicon carbide was selected.
To compare two drug delivery systems based on single-walled nanotubes, molecular dynamic simulations were applied and encapsulation behavior of the drug carboplatin was investigated inside the silicon carbide nanotube and the carbon nanotube.
Localization of the carboplatin inside the nanotubes indicated that the carboplatin moves throughout the tubes and possesses a greater probability of finding the drug molecule along the nanotubes in the first quarter of the tubes. The energy analysis exhibited the lowest free energy of binding belongs to the encapsulation of the drug carboplatin in the silicon carbide nanotube, about -145 Kcal/mol.
The results confirmed that the silicon carbide nanotube is a more suitable model than the carbon nanotube for drug delivery system based on nanotubes as a carrier of platinum-based anticancer drugs.