Showing papers in "Jundishapur Journal of Natural Pharmaceutical Products in 2017"

The Hepatoprotective Effect of Gallic Acid on Mercuric Chloride-Induced Liver Damage in Rats

Abstract: Background: Mercury has a variety of industrial applications and is well-known for its hematotoxic, hepatotoxic, neurotoxic, nephrotoxic, and genotoxic effects. Objectives: This study was carried out to assess the protective effects of gallic acid against mercuric chloride-induced oxidative stress in albino rats. Methods: A total of 35 male Wistar rats were divided into 5 groups (7 rats per group). Groups 1 and 2 were used as the negative and positive controls, respectively and received normal saline (2 mL/kg/day, po) and mercuric chloride (0.4 mg/kg/day, po) for 28 days. Group 3 only received gallic acid (200 mg/kg/day, po) for 28 days, whereas groups 4 and 5 received gallic acid (50 and 200 mg/kg/day, respectively) after 1 hour, followed by mercuric chloride (0.4 mg/kg/day, po) for 28 days. Results: The results demonstrated that treatment with gallic acid significantly diminished the mercuric chloride-induced increase in the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lipid peroxidation in liver tissues. In addition, gallic acid treatment increased the level of glutathione peroxidase, superoxide dismutase, and catalase activity and lowered the glutathione level in liver tissues, compared to the mercuric chloride group. The liver of rats, treated with mercuric chloride, showed degenerated cells (with mild cytoplasmic vacuolation and blebbing), binucleated cells, and significant sinusoidal dilation. Conclusions: It can be concluded that gallic acid restores the activities of antioxidant enzymes and tissue markers in mercuric chloride-treated rats, probably by scavenging free radicals and improving the antioxidant defense mechanisms. © 2017.

His 6 -OPH and Its Stabilized Forms Combating Quorum Sensing Molecules of Gram-Negative Bacteria in Combination with Antibiotics

Abstract: Background: In most species of gram-negative pathogenic and conditionally pathogenic bacteria, quorum sensing-dependent systems have been discovered, in which various N-acyl-L-homoserine lactones function as signaling molecules inducing the development of resistance towards the effects of antibiotics. Objectives: The purpose of this study was to investigate the possibility of stabilizing lactonase activity of His6-OPH by forming enzyme polyelectrolyte non-covalent complexes (EPNCs) containing both this enzyme and polyanionic polymer. It also targeted at studying the efficacy of these EPNCs in combination with a variety of antibiotics (ampicillin, gentamicin, kanamycin, and rifampicin) against gram-negative bacteria. Cheap non-toxic biodegradable polyamino acids (poly-L-glutamic acid and poly-L-aspartic acid) were selected as polyanionic polymers to produce EPNCs. Methods: Recombinant Escherichia coli strain SG13009 [pREP4], transformed by plasmid encoding His6-OPH, was used for His6-OPH production. The His6-OPH lactonase activity was determined according to known methods, using a pH-sensitive indicator (cresol red) and a colorimetric method. The minimum inhibitory concentration (MIC) of antibiotics was determined with the suspension of bacteria cells, with antibiotic added in a concentration range from 0 to 500 mg/L at 37°C during 16 hours. Results: All the tested enzyme preparations were equally efficient in catalyzing the hydrolysis of N-acyl-homoserine lactones of various structures containing and lacking a 3-oxo group in the acyl radical. It has been established that the presence of enzyme preparations facilitates the reduction of MIC of antibiotics (ampicillin, gentamicin sulfate, kanamycin sulfate, and rifampicin) on the growth of highly concentrated (106 cells/mL) cell populations of Pseudomonas aeruginosa B-6643 and Escherichia coli B-6645. Polyelectrolyte complexes of this enzyme have an increased efficiency at a lower pH (6.5) of the medium in comparison to its highly purified form. It is possible to reduce the minimum inhibitory concentration of antibiotics by 10% to 850% in combined use of antibiotics and His6-OPH enzyme preparations. Conclusions: The discussed approaches for the use of original biological products based on His6-OPH opens up opportunities for creating new ways of effectively controlling bacterial diseases in animals.

Evaluation of the Mosquito Repellent Activity of Nano-sized Microemulsion of Eucalyptus globulus Essential Oil Against Culicinae

Abstract: Background: The mosquitoes of Culicidae family are serious vectors of several tropical diseases, such as malaria, filariasis, encephalitis, and nuisance. Control of mosquitoes and protection of people from their bites are of the most important ways to prevent transmitted diseases. Although the efficacy of N, N-diethyl-m-toluamide (DEET) is high and generally used as mosquito repellent, yet a number of biting diptera are tolerant to DEET. Furthermore, there are concerns about the safety of DEET and its allergic and toxic effects. Therefore, it is necessary to use other repellents like plant essential oils. Objectives: The aim of this work was to develop a safe repellent with a long-lasting protection based on micro-emulsion of eucalyptus essential oil. Methods: Eucalyptus globulus essential oil was obtained by water distillation in a Clevenger apparatus. The larvae of Culicidae were collected and adult mosquitoes reared for the repellency test. Preparation of micro-emulsions of Eucalyptus globulus essential oil was made by mixing the specified surfactant (Tween 80 and Span 20) and the appropriate amount of co-surfactant (propylene glycol) under the water titration method. The laboratory method, arm in cage, was used to estimate the time of protection of essential oil micro-emulsion against mosquitoes and DEET used as a standard repellent. Results: Physicochemical properties of formulated micro-emulsions were appropriate and suitable for topical application. Particle size of eucalyptus oil 15% w/w micro-emulsion was lowest. When applying eucalyptus oil micro-emulsion at concentrations of 5, 10, and 15% w/w, time of protection against mosquitoes were 82 ± 15.8, 135.7 ± 26.4, and 170.7 ± 26 minutes, respectively. These times of protection were similar to DEET at same concentrations and significantly more than eucalyptus essential oil. Conclusions: The formulated micro-emulsion of eucalyptus oil at a concentration of 15% w/w has potential repellency to the extent of DEET. It seems that nano-sized microemulsion is stable in terms of thermodynamics and kinetics. In conclusion, preparation of nano-sized microemulsion could delay the volatility of eucalyptus essential oil and volatile oil release from formulations and consequently increase protection time against mosquitoes.

A Novel Microemulsion System for Ocular Delivery of Azithromycin: Design, Characterization and Ex-Vivo Rabbit Corneal Permeability

Abstract: Background: The poor bioavailability of ophthalmic drops is mainly due to the rapid nasolacrimal drainage of the drug and very low permeability of corneal epithelium. Hence, there is an interest to find an effective system to improve drug permeability and bioavailability. Objectives: The aim of the present study was to design and characterize a novel microemulsion system as an ocular delivery system for Azithromycin and evaluate its physicochemical characteristics and rabbit corneal permeability in order to enhance the penetration of the drug. Methods: The prepared microemulsions (MEs) were assessed for their viscosity, pH, particle size, surface tension, DSC, stability, in vitro drug release, and corneal rabbit permeability. In this study, a full factorial design was employed with 3 variables at 2 levels for preparing 8 formulations and data analysis. Results: The results showed that the average droplet size of ME formulations was in the range of 6.78 to 26.65 nm while pH values were 5.1 to 5.7 and viscosity range was 115 - 361 cps. Drug release profile revealed that 79.066% of the drug released in 24 hours of the experiment. The maximum and minimum percentages of drug permeated through rabbit cornea were observed in MEA-7 (12.87%) and MEA-2 (0.909%), respectively. All ME formulations with different compositions and properties significantly increased partitioning, flux, and permeability coefficient from rabbit cornea. Dapp and Papp parameters in MEA-1 and MEA-7 formulations were 0.00882 cm2h-1 and 2.391 cmh-1, which were 17.65, 35.17 times higher than those of control (AZ suspension, 1%), respectively. The flux (Jss) of Azithromycin in MEA-7 was 11.958 mg cm-2h-1, which was 39.86 times higher than that of control. Conclusions: The present study showed that any change in the content and composition of ME could change physicochemical properties and permeability parameters during drug permeation of ME formulations. The phenomenon may be due to the cornea structural changes in presence of ME components.

Application of Genetically Engineered Dioxygenase Producing Pseudomonas putida on Decomposition of Oil from Spiked Soil

Abstract: Background: It is well known that bioremediation or using microorganism enzymes plays an important role in decomposition and changing of oil pollutants and PAH compounds into nonhazardous or less-hazardous substances. The genetically manipulated bacteria like Pseudomonas sp. can enhancement the natural biodegradation activity of polycyclic aromatic hydrocarbons (PAHs) in polluted cities. Pseudomonas putida (P. putida) is a saprotrophic soil bacterium that is found throughout various environments such as soil and freshwater environments. Oil and petroleum industries are important exposure of PAHs in environment that strongly associated with the development of human cancers. Objectives: In the present work, P. putida was genetically manipulated for the biodegradation of oil in spiked soil and its activity was measured using the high-performance liquid chromatography (HPLC) method. Methods: The catechol 2,3-dioxygenase (C23O) encoded gene (nahH) was cloned into pUC18 for generating pUC18-nahH. This recombinant vector was transferred into P. putida, successfully, and both wild type and genetically modified P. putida were inoculated in spiked soil with oil for pilot plan preparation. Then, biodegradation activity of this bacterium on the elimination of phenanthrene and pyrene as an oil indicator in spiked soil were evaluated by the HPLC measurement technique. Results: The results showed the biodegradation of these PAH compounds in oil-spiked soil by genetically manipulated P. putida in both groups (containing autoclaved soil and dish containing natural soil) comparing to the inoculated group by wild type of P. putida were statistically significant (P < 0.05). Finally, confirmatory tests (catalase, oxidase, and PCR) were accomplished on isolated bacteria from spiked soil and were indicated that engineered P. putida was alive and functional by producing the C23O enzyme for biodegradation activity of oil. Conclusions: These findings demonstrated a degradable strain of P. putida that was generated in this study by genetic engineering can be useful to assess biodegradation of PAHs compounds in oil and petrochemical pollutions.

Identification and Quantification of Phthalate Pollution in Holothuria atra : A Sea Cucumber from the Persian Gulf (Iran)

Abstract: In recent years, microplastics have accumulated in oceans and sediments worldwide. Due to their small size, microplastics may be ingested by low trophic fauna, with uncertain consequences for the health of the organism. Sea cucumbers are one of the major echinoderms from the class Holothuroidea that ingest plasticizers in their mouth and filter the water. Regarding the recent interests on probable pollution of medicinal plants and other natural medicines, like marine organisms to phthalates, in this study a phthalate ester was isolated from Holothuria atra of Persian coasts for the first time. The structure of the compound was elucidated using spectroscopic data (IR, NMR and MS) and the compound was used as a standard for quantification of microplastic in H. atra, a marker of pollutant in the Persian Gulf. Quantification was done by high performance thin layer chromatography and the amount of bis (2-ethylhexyl) phthalate (BEHP) was 0.15 ± 0.08 mg/g.

A Simple Method for Extraction and Purification of Hypericins from St John’s Wort

Abstract: Hypericin was extracted from Hypericum perforatum L. using a different extraction procedure. Highest amounts of hypericins were extracted by ultrasonic methods using methanol: acetone 2:1 as an extracting solvent. Hypericin contents of the extract was purified by passing it through 2 series of 70 × 5 mm glass columns, each filled with 800 mg of 35 - 70 mesh silica gel, followed by elution with MeOH: acetone: CH2Cl2 (75:10:15). The extent of purification was determined by HPLC. The amount of purified hypericins, which was extracted from Hypericum perforatum, was 5.105 mg per gram dried plant leaves.

Evaluation of Antimicrobial Activity of Eucalyptus camaldulensis Essential Oil Against the Growth of Drug-Resistant Bacteria

Abstract: BackgroundDue to the increasing resistance of pathogenic bacteria to common antibiotics, researchers are seeking alternative antimicrobial agents with plant origins.ObjectivesThe purpose of this study was to evaluate the activity of essential oil, extracted from the leaves of Eucalyptus camaldulensis, the major Eucalyptus species cultivated in Khuzestan, South of Iran, against the growth of drug-resistant bacteria.MethodsEssential oil was extracted from the leaves using the hydrodistillation method in a Clevenger apparatus. The constituents of the essential oil were determined by gas chromatography-mass spectrometry (GC-MS). Moreover, the antimicrobial activity of essential oil was assayed using the disk diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were also determined using the macrodilution method.ResultsIsolation and identification of the main components of essential oil identified 1,8-cineole (55.2%) as the main component. The essential oil could control resistant pathogenic bacteria. The greatest effect of essential oil was reported against Klebsiella pneumoniae with an inhibition zone diameter of 35 mm and MIC and MBC of 500 and 1500 ppm, respectively. On the other hand, the lowest effect was reported against Salmonella infantis and Salmonella enteritidis with an inhibition zone diameter of 11 mm and MIC and MBC of 6,000 and 8,000 ppm, respectively.ConclusionsThe essential oil of E. camaldulensis (Myrtaceae family) grown in Iran exhibited significant activities against some Gram-positive and Gram-negative bacteria. Therefore, E. camaldulensis is an effective antibacterial and bactericidal agent in the treatment of infectious diseases

Effects of Thymoquinone on IL-6 Gene Expression and Some Cellular Signaling Pathways in Prostate Cancer PC3 Cells

Abstract: Background: Thymoquinone (TQ), a bioactive compound, has many pharmacological actions especially anticancer effects. Prostate cancer (PC) is one of the most common malignancies among males in the world. Objectives: The current study aimed at evaluating the effects of TQ treatment on interleukin-6 (IL-6) expression, IL-6 secretion, cell viability, phosphorylated extracellular signal–regulated kinases (pERK1/2), phosphorylated AKT (pAKT), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) signaling pathways in human prostate cancer PC3 cells. Materials and Methods: PC3 cells were cultured in different concentrations of TQ for 48 hours. Cell viability, expression, and secretion of IL-6 were assessed by MTT assay, real-time quantitative polymerase chain reaction (RT-q PCR) analysis, and the enzyme-linked immunosorbent assay (ELISA) technique, respectively. The changes of pERK1/2, pAKT, and pSTAT3 were determined using Western blot procedure. Results: Treatment with TQ caused the reduction of viability (inhibitory concentration [IC50] = 45 µM) and survival in PC3 cells. RT-q PCR had a significant reduction (P < 0.05) in IL-6 gene expression compared with the control cells (50%, 59%, 68%, and 70% at 30, 40, 45, and 50 µM of TQ, respectively). TQ treatment resulted in a significant decline (P < 0.05) in the secretion of IL-6 compared with the control cells (56.89%, 71.12%, 84.32%, and 85.89% at 30, 40, 45, and 50 µM of TQ, respectively). Western blot showed a reduction in the phosphorylated STAT3, AKT, and ERK proteins. Conclusions: The obtained results suggested that TQ can effectively reduce IL-6 signaling pathways (pSTAT3, pAKT, and pERK1/2). Also, TQ can decrease IL-6 gene expression, which leads to the reduction of cell proliferation and viability. Therefore, TQ may be beneficial to treat prostate cancer.

Safety Assessment of Osthole Isolated from Prangos ferulacea : Acute and Subchronic Toxicities and Modulation of Cytochrome P450

Abstract: Background: Osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural coumarin derivative, has exhibited various pharmacological properties. In addition, the possibility of its development as a promising lead compound for drug discovery has been proposed. However, there is little toxicological information regarding safety of repeated exposure to this coumarin. Objective: The present study evaluated the potential toxicity of osthole after acute and subchronic administration in rodents. In addition, we investigated the effect of osthole on different hepatic CYP gene expressions in male rats receiving the highest dose of osthole. Methods: In the acute toxicity study, single doses of osthole (100, 500, and 1000 mg/kg) were administered intraperitoneally to mice and the mice were then monitored for 14 days. In the subchronic toxicity study, osthole was administered orally to rats at doses of 5, 25, and 50 mg/kg/day for 45 days. Results: The results of acute study indicated that LD50 of osthole is about 710 mg/kg. There was no significant difference in body weight, relative organ weight, and hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes including in creatinine, potassium, glucose, albumin, and urea levels. The results of histopathological studies showed that all the removed organs, specially kidney, were affected by subchronic exposure to osthole. The change in the kidney included peritubular capillary congestion, hemorrhage in renal parenchyma, mild tubular dilatation, and mild interstitial infiltration of inflammatory cells. Furthermore, osthole treatment caused an induction in CYP1A2, CYP2E1, and CYP2C11. Conclusions: Finally, concerning the common classification of relative toxicity of chemicals, acute toxicity results suggested that osthole is a moderately toxic substance when administered i.p. The obtained data from subchronic study supported the evidence of renal function impairment by osthole. The no-observed adverse-effect level (NOAEL) of the extract for both male and female rats is considered less than 5 mg/kg.

Ameliorative Effects of Red Lentil Extract on Sodium Arsenite-induced Oxidative Stress in Rats

Abstract: Background: Arsenic is a potent environmental toxic agent and leads to the development of various hazardous effects on human health. All human populations are exposed to arsenic and its compounds through occupational or environmental processes. Epidemiological studies also suggested that lentils through a numerous biological activities including antioxidant, anticancer, angiotensin-converting enzyme inhibition, as well as reducing blood lipid and the risk of cardiovascular diseases admit protection against chronic diseases. Objectives: The current study aimed at assessing the protective effect of the red lentil extract (RLE) on sodium arsenite (SA) induced oxidative stress in animals. Methods: Twenty-four Wistar male rats were divided into 4 groups. The first group (control group) received normal saline (2 mL/kg) per os for 25 days. Groups 2 - 4 were treated with SA (10 mg/kg) per os for 10 days; and the groups 3 and 4 received 100 and 200 mg/kg of RLE per os for 15 days, respectively, after treatment with SA. Results: Results showed that total phenolic content in crude RLE was 50.6 mg catechin equivalent/g of dry weight. In SA treated groups, serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lipid peroxidation (MDA) in the liver increased. Whereas, the activity of superoxide dismutase (SOD) and catalase and the content of sulfhydryl groups (SH-groups) significantly decreased in liver in the intervention group, compared with those of the control group (P < 0.05). Treatment with RLE reduced the serum level of AST, ALT, and ALP and the level of MDA in the liver, while the activity of the antioxidant enzymes and the level of SH-groups increased. Conclusions: It can be concluded that RLE restored the activity of antioxidant enzymes and serum markers in SA-treated rats, probably by scavenging free radicals and reducing oxidative stress as an antioxidant. © 2017, Jundishapur Journal of Natural Pharmaceutical Products.

Biological and Phytochemical Screening of Eremostachys azerbaijanica Rech.f. Aerial Parts

Abstract: Background: Eremostachys azerbaijanica rech.f. is an endemic species with an anti-inflammatory effect in Iranian folk medicine. Objectives: The aerial part extracts of Eremostachys azerbaijanica were investigated for their general toxicity, antibacterial and anti-proliferative activities. Moreover, preliminary phytochemical investigations were carried out on the extracts. Methods: Brine shrimp lethality test was performed to evaluate general toxicity. Anti-proliferative and anti-bacterial activities were evaluated by (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and disc diffusion methods. Additionally, all the extracts were tested for the presence of various phytoconstituents by different reagents. Results: In our research, the n-Hexane extract situated the greatest active part in the brine shrimp lethality test, whereas methanol (MeOH) extract didn’t show substantial effect. MTT assay was carried out on one normal cell line and 2 cancer cell lines including the human umbilical vein endothelial cells (HUVEC), the human colon adenocarcinoma (HT29), and the human lung carcinoma (A549), respectively. The end results indicated that the n-Hexane and dichloromethane (DCM) extracts possessed potent anti-proliferative effects against HT29 and A549 cell lines. Interestingly, none of these 3 extracts showed any important effect against HUVEC cells. As a final point, these 3 extracts didn’t have any antimicrobial activities against gram positive, gram negative, and Candida albicans species. Conclusions: n-Hexane extract had the maximum cytotoxicity against Artemia salina and A549 cells, whereas DCM extract was the most potent fraction against HT29 cell line. Preliminary phytochemical screening indicated that the DCM and n-Hexane extracts contained sterols, triterpenoids and cardiac glycosides, which might cause the observed anti-proliferative activity.

The Effects of Pomegranate ( Punica granatum L.) Peel Methanolic Extract on Methotrexate Induced Changes in Hepatic Antioxidant Enzymes of Rats

Abstract: Background: Methotrexate (MTX), as one of the most pivotal drugs in treatment of some malignancies and autoimmune diseases, is associated with damages to different tissues particularly the liver tissue through impairing the balance between antioxidant and pro-oxidants. Pomegranate peel is a great source of polyphenols with antioxidant function that has recently become a center of attention. Objectives: The current study was undertaken to investigate the effects of MTX and pomegranate peel methanolic extract (PPME), alone and in combination, on liver antioxidants of rats. Methods: Antioxidant capacity, total phenolic and flavonoid contents of PPME were analyzed. 32 rats were divided into (1) control, (2) orally received 500 mg/kg PPME, (3) intramuscularly received 10 mg/kg MTX, and (4) PPME (for 18 days) and MTX (for 3 days beginning from the 10th day) groups. After the experimental period, the rats were euthanatized and tissue samples were obtained for antioxidant analysis. Results: PPME had a considerable antioxidant capacity, as well as total phenolic and flavonoid contents. There were low liver contents of Glutathione peroxidase (GPx) and Catalase and a high level of Malondialdehyde and Superoxide dismutase (SOD) in the Methotrexate group compared to the control group (P < 0.05). In the Methotrexate-PPME group, PPME could increase the GPx and Catalase contents and decrease the SOD content of the liver compared to the Methotrexate group. GPx of liver samples in the PPME group decreased (P < 0.05). GPx decreased and Malondialdehyde increased in the Methotrexate-PPME group compared to the control group (P < 0.05). Conclusions: Methotrexate can surprisingly increase SOD and Malondialdehyde and decrease Catalase contents. PPME can decrease GPx and relatively prevent the effects of Methotrexate on SOD and Catalase contents of the liver tissue. However, further studies are recommended.

Evaluation of Phytochemistry and Some Biological Activities of Aerial Parts and Seed of Scrophularia Umbrosa Dumort

Abstract: Background: Scrophularia umbrosa is a plant used as a traditional herb. Objectives: This study was designed to investigate the antimalarial activity and free radical scavenging of methanol, DCM and n-Hexane extract of aerial parts and seed, as well as total phenol, total flavonoid contents, and phytochemical identification. Methods: GC-MS technique were used for identification of the chemical compositions of the DCM and n-Hexane extract as well as HPLC and NMR techniques for methanolic extract. The hemozoin formation has been suggested as a desirable drug target to antimalaria sieve scheme. In the present study, we used the spectrophotometric assay to screen the potency of plant extracts. The DPPH method has been used for antioxidant activity screening of the extracts and fractions. AlCl3 and Folin -Ciocalteu reagents, respectively, were used for total flavonoid and total phenol contents of samples. Results: Our results showed that n-hexane and the MeOH extracts of the aerial parts, and seed did not display any impressive prevention of heme biocrystallization confidants, however, the DCM extract of aerial part, in the comparison with the blank, showed slightly antimalarial effects. Furthermore, fractions (20%, 40%, and 60%) of MeOH extracts of aerial part and seed of S. umbrosa had moderate to strong antioxidant activity and it is possible to conclude that there is a positive relation between phenolic and flavonoid compositions as well as antioxidant activity. GC-MS data showed that volatile portions of DCM and n-Hexane extracts of various organs from S. umbrosa are containing few identifiable compounds. In addition, Aucubin and Luteolin-7-O-rutinoside were also recognized from MeOH extracts. Conclusions: Based on the results, the fractions of extracts could be evaluated by 1HNMR for predicting of groups of natural compounds as well as interfacing chemical and biological assessments.

Effects of Crocin on Spatial Memory Impairment Induced by Hyoscine and Its Effects on BDNF, CREB, and p-CREB Protein and mRNA Levels in Rat Hippocampus

Abstract: Background: Crocus sativus L., (Iridaceace), known as saffron, is used in traditional medicine for different purposes such asmemory improvment. Crocin is one of the pharmacologically active constituents responsible for many medicinal properties of saffron. Objectives: In this study, the effects of crocin, an active saffron constituent, on hyoscine inducedmemory impairment and its effect onprotein andmRNAtranscript levels of CREB (cAMP response element binding protein), BDNF(brain-derived neurotrophic factor), and phospho-CREB (p-CREB) were investigated in rat hippocampus. Methods: Rats were intraperitoneally treated with crocin (10, 20, and 40 mg/kg), normal saline (1 mL/kg), and rivastigmine (1.5 mg/kg) 30 minutes prior to hyoscine (1 mg/kg) for five days. The effects were studied on spacial learning and memory using Morris water maze. Protein and transcript levels of CREB and BDNF were analyzed using western blotting and qRT PCR methods, respectively. Results: Five days treatment with crocin (20 and 40 mg/kg) and rivastigmine significantly increased the presence of animals in target quadrant in probe trial on the 8th day compared to hyoscine. Crocin (20 mg/Kg) increased significantly BDNF and CREB protein and transcript levels compared to hyoscine. Conclusions: Crocin improved memory impairment induced by hyoscine through reduction of the latency to find the platform in the probe trial in Morris water maze test. Crocin improved memory probably due to the increase of BDNF and CREB protein and transcript levels. © 2017, Jundishapur Journal of Natural Pharmaceutical Products.

The Protective Effects of Hydro-Alcoholic Extract of Coriandrum sativum in Rats with Experimental Iron-Overload Condition

Abstract: Background: Development of a new iron-chelating medication may eventually serve as treatment of iron overload diseases, such as thalassemia and other iron related disorders. Coriander sativum, a plant rich of phenol and flavonoids, has an iron-chelating effect in-vitro. The ethanolic extract of C. sativum was investigated for its in-vivo ameliorating effect on hepatic damage in rats with experimental iron overload. Methods: Twenty-four adult male wistar rats were randomly divided to 4 groups: healthy control, iron overload, iron overload treated with deferoxamine, and 200 mg/kg of C. sativum extract, respectively. Assessments were performed for serum iron, ferritin, and serum markers of hepatic and cardiac damages, antioxidant enzyme, and lipid peroxidation levels. Results: The results indicated serum iron and ferritin concentration were significantly increased in the iron overload group compared to healthy controls (P < 0.05). Treatment with the C. sativum extract significantly decreased iron and ferritin concentration (P < 0.05). Histopathological changes in the liver, kidney, and the cardiac system, and iron accumulation in the liver were observed in the iron overload group compared to healthy controls (P < 0.05). Treatment with C. sativum extract significantly decreased biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and improved tissue damage and decreased iron accumulation in the liver compared to the iron overload group (P < 0.05). Conclusions: The study showed that the hydro-alcoholic extract of C. sativum has iron-chelating and liver protective effects similar to deferoxamine against experimental iron overload condition in rats.

Evaluation of Serum Vitamin D Levels in Patients with Vitiligo Undergoing NBUVB (Narrowband UV-B) Therapy

Abstract: Background: Vitamin D increases the contents of tyrosinase in cultured human melanocytes, which raises its possible role in modulating melanogenesis. Objectives: In this study, the level of 25 (OH) D was measured before and after NBUVB therapy and its relationship with outcome of NBUVB therapy in patients with vitiligo was also assessed. Methods: This study was conducted on 30 patients with generalized vitiligo (less than 30% body surface) and 30 healthy individuals without age and gender limitations. The patients received NBUVB therapy 2 times a week for 15 weeks. We measured the serum vitamin D level and involvement area (VASI score, vitiligo area, and severity index) at baseline and 30 sessions post treatment. Results: The level of vitamin D increased significantly compared to baseline measurements. Vitamin D level changes were not significantly associated with clinical outcome in which VASI score decreased. Conclusions: Vitamin D did not improve clinical outcomes. Thus, we suggest that further studies be conducted to understand the mechanisms of pigmentation due to NBUVB therapy in vitiligo.

The Vitamin E Preventive Effect on Taxol-Induced Neuropathy Among Patients With Breast Cancer: A Randomized Clinical Trial

Abstract: Background: Chemotherapy-induced neuropathy is one of the most severe complications of cancer drug therapies causing a number of problems for patients and making treatment limitation decisions problematic. One of the most important drugs used in breast cancer chemotherapy regimens, Taxol is considered as the most common cause of neuropathy in such cases. The aim of this study was to evaluate the effect of vitamin E on reducing the Taxol-induced neuropathy development among patients with breast cancer. Methods: The randomized clinical trial (RCT) included 70 patients with breast cancer who received Taxol chemotherapy regimens. They were assigned to one of the two groups: a group without vitamin E feeding (Group I) and a group with vitamin E treatment at a daily dose of 400 IU bid (Group II). Electrophysiological testing of all patients was performed before starting medications and again 3 months post-treatment. The data were compared between the groups. Results: Vitamin E feeding had no significant effect on amplitude, latency, and CV of tibial and peroneal nerves (P > 0.05), while the delta amplitude of sural nerve was significantly lower among patients taking vitamin E supplements (P = 0.007). Conclusion: We suggest the inhibitory effect of vitamin E on the progression of Taxol-induced neuropathy, by slowing the speed of progression, among breast cancer patients by improving the function of the nervous system.

Antibacterial Evaluation and Biochemical Characterization of Thais savignyi Gastropod Extracts from the Persian Gulf

Abstract: Objectives: This study aimed to screen Thais savignyi whole body extracts for antibacterial activity against clinical isolates of some human pathogenic bacteria and analyze its biochemical compounds, including carbohydrate, proteins, alkaloids, cholesterol, unsaturated fatty acids, as well as functional groups and elements. Methods: Well agar diffusion was used for screening of acetone and methanol extracts against clinical isolates of E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus cereus, and Staphylococcus aureus. Biuret and SDS-PAGE methods were applied for quantitative and qualitative protein evaluation. Anthrone method was used for quantitative and qualitative analysis of carbohydrates. Wagner and Mayer's reagents were employed for alkaloid screening. The Liebermann-Burchard test was performed for the detection of cholesterol, infrared for identifying functional groups, and Dumas method for elemental analysis. Results: Acetone and methanol crude extracts at 0.2 mg/mL concentration inhibited the growth of all the test bacteria; however, the methanol extract was more effective than the acetone extract. The maximum zone of inhibition of the methanol extract was observed against B. cereus (16 mm). Minimal inhibitory concentration of the most effective fraction ranged between 12.5 and 100 µg/mL. Elemental analysis of the bioactive fraction showed 41.55% carbon, 9.49% hydrogen, 6.13% nitrogen, and 1.64% sulfur. IR spectra confirmed the presence of aliphatic, alkenes, secondary amines, and disulfide groups in the most effective fraction of methanol extract of Thais savignyi. Carbohydrate and protein analysis revealed 4.5% carbohydrate and 9% protein. SDS-PAGE disclosed 5 separate bands with 70, 53, 41, 30, and 22 kilodaltons. Wagner and Mayer test showed the presence of alkaloids; mercuric and iodine solutions indicated the presence of unsaturated fatty acids; cholesterol was detected by Liebermann-Burchard reaction and Salkowski test. Conclusions: The findings of this study suggest that Thais savignyi has antibacterial potential and can be recommended as a source of bioactive compounds of medicinal value.

Tailored Hydrogel Microbeads of Sodium Carboxymethylcellulose as a Carrier to Deliver Mefenamic Acid: Transmucosal Administration

Abstract: Background: Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs produce an enhanced hazard of severe gastrointestinal adverse effects, specifically in elderly patients. Objectives: The current study aimed at formulating mucoadhesive microparticles of mefenamic acid to improve the therapeutic efficacy and patient compliance Methods: The microparticles were prepared by ionic gelation method sodium carboxymethyl cellulose (Na CMC) polymer. In the current study, the buccoadhesive microspheres holding various polymer-to-drug ratios were prepared and characterized by the following properties: encapsulation efficiency, FTIR (Fourier transform infrared) flowability, particle size, degree of swelling and surface pH, DSC (differential scanning calormetric), mucoadhesive property, retentive time, and release of drug Results: The best polymer-to-drug ratio in the microspheres was 4:1 (as F3). The production yield of F3 microparticles showed a mean of 99.30%, with a particle size of 1905.46 µm and loading efficiency of 46.56%. The DSC showed that the mefenamic acid-loaded microparticles changed to amorphous form. Based on the FTIR results, the drug maintained its chemical stability during the encapsulation process. It was found that the prepared F3 microparticles had more release rate than the microparticles of F1, F2, and untreated mefenamic acid powder (P < 0.05). The microparticles exhibited very good retention time properties. The results of mucoadhesive strength and surface pH of discs showed better characterization of microparticles in buccal administration. Conclusions: The formulations were appropriate candidates to improve microparticles for the remedial purposes.

Efficacy Evaluation of Nebulized Magnesium, as an Additional Complementary Treatment, in Clinical and Peak Flow Metric Improvements of Acute Asthma Attack: A Randomized Double-Blinded Clinical Trial

Abstract: Background: Exacerbation of acute asthma attacks is a medical challenging problem that affects health systems all around the world. According to the reports, acute asthma has allocated about 1 to 12% of adults’ referral to the emergency departments by itself. This study aimed to investigate the effect of additional nebulized magnesium sulfate, as an additional complementary treatment, on the management of acute asthma attack. Due to controversies and the fact that previous research has been unable to confirm the benefits of routine use of magnesium in the course of treatment of asthma acute phase, this trial was conducted. Methods: Patients with a possible clinically suggested acute asthma attack, aged 18 to 65, were divided into two groups of intervention and control. An initial peak flow meter evaluation at arrival identified the severity of patients’ asthma attack. 148 patients with moderate to severe attacks were included in the study in two groups. Patients of the control group received standard asthma treatment consisting of nebulized albuterol 2.5 mg and nebulized ipratropium bromide 0.5 mg, both in minutes 0, 20, and 40 after arrival and oral single-dose prednisolone 50 mg at arrival. Patients of the case group received additional doses of nebulized magnesium sulfate 0.3 g in minutes 0, 20, and 40 after arrival in addition to the standard treatment performed on the control group. The clinical setting of dyspnea Borg scale in both the case and control groups, as well as their PEFR and FEV1 values, were recorded during the trial in minutes 0, 20, 40, and 60 after arrival. Chi-square, T-test, and Mann Whitney test were applied for data analysis. Results: The study was conducted on 148 subjects who were divided into two groups of 75 and 73 as case and control groups, respectively. PEFR values in minutes 40 and 60 after arrival were 295.04 and 336.2 in the case group and 249.64 and 282.86 in the control group, and there was a significant difference in the PEFR improvements between the case and control groups (P < 0.001). In addition, FEV1 in minutes 40 and 60 after arrival was respectively 2.26 and 2.66 in the case group and 1.88 and 2.23 in the control group. There were significant differences in FEV1 improvements between the case and control groups (P < 0.001). Conclusions: According to the results of this study, it can be concluded that administration of nebulized magnesium sulfate as an adjunctive medication to the standard treatment is beneficial in the management of moderate to severe acute asthma attacks and significantly leads to better control of acute attack in short term.

Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease

Abstract: Background: Alzheimer’s disease (AD), the most typical type of dementia and memory loss, is a complicated and progressive neurodegenerative disorder. Due to the multi-factorial etiology of AD, the multi-target-directed ligand (MTDL) approach can be a potential method in seeking new drug candidates for this disease. Methods: In this study, over 200 tacrine-naphtoquinone hybrids have been designed and their drug-likeness, molecular docking, and descriptor analysis were conducted to find out a drug candidate with less toxicity and better binding affinity than tacrine. The Docking analysis was conducted using human acetylcholineesterase (1ACJ), human butyrylcholineesterase (4BDS), and β-secretase (BACE1) (1w51) enzymes using Autodock 4.2 and Vina. Results: Promising results were obtained on the types of interactions. Based on molecular docking on 3 targets as well as protein ligand interaction fingerprint (PLIF) studies, the compounds with better results were introduced as good candidates for synthesis. The validity of docking protocols was confirmed using a set of familiar active ligands and decoys on these targets by means of 2 known statistical metrics such as the receiver-operating characteristic (ROC) and Enrichment Factor (EF). Conclusion: Structure activity relationship (SAR) studies, in these class of compounds, show that the hydroxyethylamine, as a linker, is an essential group to improving binding site to AChE and BACE-1 targets.

The Contractive Effect of Rubia tinctorum L. Extract on the Isolated Aorta Smooth Muscle and Its Protective Effect Against the Damage Caused by Hyperglycemic Solution in Rat

Abstract: Background: Few past studies have indicated antispasmodic and anti-oxidative effects of some species of Rubiaceae. Objectives: This study aimed to investigate the effect of hydroalcoholic extract of Rubia tinctorum L. (madder) root on the rat-isolated aorta and possible protective effects against the damage caused by hyperglycemic environment. Methods: The isolated thoracic aorta ring (with or without endothelium) was treated with phenylephrine (10-6 M) or KCl (80 mM) plus madder (0.1, 0.5, 1, and 5 mg/mL) and madder alone. The effect of madder alone and combined with phenylephrine (10-6 M) was studied in Ca2+-free Krebs. To investigate the effect of madder on aorta under oxidative stress, the aorta response to acetylcholine (10-5 M) following three hours incubation with high glucose (44 mM) with or without madder (0.5 mg/mL) was measured. Results: Madder did not have any significant effect on pre-contracted aorta with phenylephrine or KCl; however, madder alone could contract aorta concentration dependently (P < 0.01). In Ca2+-free Krebs, the contractile responses of aorta to madder or madder plus phenylephrine reduced up to 60% (P < 0.05). After three hours incubation of aorta ring with high glucose, aorta response to acetylcholine was vasoconstriction. Adding 0.5 mg/mL madder to hyperglycemic solution apparently preserved acetylcholine vasodilatory effect on aorta (P < 0.01). Conclusions: Our findings suggest that madder induces a vasoconstriction effect on aorta in vitro, which probably is related to facilitated entry and sensitivity of muscle cells to calcium. Madder also may have protective effects in aorta, probably against oxidative damage of high concentration glucose.

Withania coagulans Protects Striatum from Oxidative Damages Induced by Global Brain Ischemia in Rat

Abstract: Background: Withania coagulans is a traditional plant that possesses diverse pharmacological characteristics including anti-hyperglycemic, anti-hyperlipidemic, antitumor, anti-inflammatory, and antioxidant effects. Objectives: This study evaluated the effect of preischemic administration of Withania coagulans extract (WCE) on antioxidant status and histopathological alteration of the striatum region in rat model of brain global ischemia reperfusion (I/R). Methods: 48 male Wistar rats were divided into four groups (n = 12): Control, Sham operated (Sham), I/R, and WCE + I/R. The animals received WCE or distilled water by oral gavage for 30 days before I/R except the control group. I/R was induced by two common carotid obstructions for 30 minutes. Three days following I/R, the animals were sacrificed, the brain was removed, and striatum was dissected out. Antioxidant statuses such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and malondialdehyde (MDA) level were measured and histological alteration was investigated in corpus striatum by Nissl and TUNEL staining. Results: The results showed that the CAT, SOD, and GPx activities decreased and MDA level increased in I/R group compare to the control group. Preischemic administration of WCE significantly decreased MDA level and increased antioxidant statuses in the striatum region compared to I/R group (P < 0.001). Histopathological analysis revealed that pretreatment with WCE markedly decreased necrotic and apoptotic neurons (P < 0.001) in striatum and reduced white matter injury induced by I/R. Conclusions: We concluded that WCE by its antioxidant and anti-inflammatory effects could modify ischemia reperfusion damage in rat striatum.

Ethnobotanical Survey: A Comprehensive Review of Medicinal Plants Used Against Gastrointestinal Disorders in Niger, West Africa

Abstract: Context: Gastrointestinal tract, a part of thehumandigestive system, is an important organ that is vulnerable to different disorders contributing substantially to morbidity and mortality rates worldwide, including in Niger. The majority of the people in Niger still use local medicinal plants to treat these ailments. This study aimed at reviewing the past and actual knowledge about the medicinal plants used to treat gastrointestinal disorders by Nigerien people of different provinces. Evidence Acquisition: Relevant data about the plant species used to treat gastrointestinal tract disorders were extracted from different studies and reports of the past and current ethnobotanical surveys conducted in Niger for a comprehensive review and a national scale analysis of their use. A statistical approach was used to determine the relative importance index in order to rank all species according to their usefulness. Results: A total of 140 plant species belonging to 50 families were recorded as being used by the Nigerien population to treat gastrointestinal disorders. Combretaceae (16/50), Mimosaceae (14/50), Caesalpiniaceae (13/50), and Fabaceae (12/50) were the botanical families with the most used species. In this review, Lannea acida, Acacia nilotica, Balanites aegyptiaca, Bauhinia rufescens, Boswellia dalzielli, Combretum micranthum, and Ziziphus mauritiana were ranked as the most cited plants. Phytochemical analyses of the plant extracts revealed the presence of tannins, terpenoids, steroids, and alkaloids in most of the plant species. Conclusions: The review and analysis of the medicinal plants reported through several ethnomedicinal surveys conducted in Niger have permitted to precisely provide substantial detailsonthe medicinal use of certain plants best to treat gastrointestinal disorders. These baseline comprehensive data could certainly attract most investigators to initiate further research that might lead to the development of new lead-drugs for the treatment of gastrointestinal disorders.

Virus Reduction of Human Plasma-Derived Biological Medicines

Abstract: Context: Biological plasma-derived medicines play an important role in the treatment and also prevention of many diseases. The technique implemented to produce such medicines should ensure to minimize the risk of pathogen infection. A very crucial step is the removal or inactivation of highly pathogenic plasma viruses, and only achieving the highly pure product is not adequate. Evidence Acquisition: In the current study, a wide range of physical, chemical, and physicochemical methods of virus inactivation and virus removal were studied to minimize the virus contamination risk in plasma-derived medicines. Results: The virus removal or virus inactivation procedures showed that they were the quite effective techniques in pathogen reduction. But, some of these methods such as solvent/detergent were only effective on lipid-enveloped viruses, while other techniques can be effective both for lipid-enveloped and non-enveloped viruses. Conclusions: To inactivate or remove the most range of viruses, at least 2 different virus inactivation or virus removal techniques should be implemented. But, still emerging new pathogens cause a serious challenge in terms of blood safety, and consequently, safety of human plasma-derived medicines.

A Comparison between the Analgesic - Sedative Effects of Ketamine and Nitrous Oxide in Bones’ Fracture Pain Control: A Randomized Clinical Trial

Abstract: Background: Analgesics such as opioids are commonly used for pain control in emergency departments. correlated respiratory side effects and central nervous system depression confine opioids application as analgesic medication. New pain control choices such as Nitric oxide and Ketamine may be alternatives. This study evaluates efficacy of Nitric Oxide versus Ketamine in purpose of pain reduction in limbs fractures. Methods: In a randomized clinical study, 75 patients that were referred to the emergency department with pain, which has been caused by bone fractures, were randomly assigned into 2 groups: receiving ketamine with an intravenous bolus dose of 0.3 mg/kg versus mixture of 50% nitrous oxide/50% Oxygen. The pain score in the groups were measured and compared by the Visual Analog Scale consecutively at arrival and 5, 10, 15 minutes after intervention. Results: Fifteen minutes after the intervention, the score of pain in patients receiving ketamine, reached 2.5 from 8.86 at the baseline. This is while in the second group, 15 minutes after the treatment, reached to 5.02 from 9.52 at the baseline. The amount of pain reduction in both groups was statistically significant. A point-by-point comparison of the amount of the pain did not show significant differences in both groups. Conclusions: The findings of this study showed that both ketamine and Nitrous Oxide/Oxygen mixture are effective in alleviating the pain of patients with limb’s fracture, however, there is no precedence between these medications as a pain killer.