European Pharma Congress August 25-27, 2015 Valencia, Spain

Byung Hwa Jung has completed her Ph.D from Seoul National University at 2000 and postdoctoral studies from University of North Carolina at Chapel Hill, school of pharmacy at 2004. She is a principal researcher and Center Head of Molecular Recognition Research Center, at Korea Institute of Science and Technology (KIST). She is also an adjunct professor of University of Science and Technology. She has published more than 60 papers in reputed journals and serving as an editorial board member of repute.

Quantitative analytical method for the simultaneous detection of celecoxib and its two main metabolites, hydroxycelecoxib (celecoxib-OH) and celecoxib carboxylic acid (celecoxib-COOH),in rat plasma was developed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed. The plasma sample was prepared through simple protein precipitation, and the reconstitution solution (0.1% formic acid in 50% methanol) was optimized to achieve the best peak shape and recovery. The analytes were separated using an Atlantis T3 column (2.1 mm × 100 mm, 3m), and the mobile phase was composed of 10 mM ammonium formate in either 5% acetonitrile or 95% acetonitrile. The detection of the analytes was performed in alternating polarity switching mode using electrospray ionization. As celecoxib-OH and celecoxib-COOH were slightly unstable following freeze–thaw cycles and long-term storage at −80◦C in stability tests, every analysis was carefully conducted with one-freeze thaw cycle and a short storage duration (<1 week). Acceptable accuracy (<15%) and precision (<15%) were obtaine din intra- and inter-day validations. The method was successfully applied to the pharmacokinetic study of celecoxib, celecoxib-OH and celecoxib-COOH following the oral administration of celecoxib in rats at a dose of 10 mg/kg. Comparing the related pharmacokinetic parameters of celecoxib and its metabolites, celecoxib was quickly metabolized into celecoxib-OH and subsequently converted to celecoxib-COOH in short intervals. The AUCs for the two metabolites were less than 10% of that for celecoxib, indicating that the rate of celecoxib metabolism was low.

Youngjoo Kwon received a PhD in chemistry from University of Houston in 2002 with studying on the determination of structure of DNA complexed with anticancer molecule, neocarzinostatin. She was a Postdoctoral fellow at Baylor College of Medicine and extended her research interest into chemical genomics. She joined the faculty at College of Pharmacy, Ewha Womams University in 2005, where she is currently a Professor. She has published more than 82 papers in reputed journals and has been serving as an Editorial Board Member of four reputed journals.

Human topoisomerases (topos) resolve DNA topological problems, unavoidably caused during DNA transcription, replication, recombination, and segregation of two identical copies of genomes in two daughter cells following replication. Topos can be grouped into two types according to the number of strands cleaved in one round of action. Topoisomerase type I (topo I) cleaves one strand of a DNA double helix while topoisomerase type II (topo II) cleaves both strands of one DNA duplex to make another non-cleaved duplex pass through a transient, topoII-mediated break and then followed by re-annealing the cleaved strands. Topo II is distinct from topo I in that topo II acts as a homodimer, requiring Mg (II) and ATP hydrolysis for enzyme turnover and rapid kinetics; this enables it to cut both DNA strands simultaneously. In addition, topo II is the only enzyme available to disentangle the topological problems in chromosomes, which must occur during DNA replication, and to decatenate the replicated chromosomes by introducing transient double strand breaks. Therefore, topo II has been targeted to develop chemotherapeutic drugs for long time. We have been studying to develop topo I- and/or topo II-targeting anticancer agents by synthesis of various flexible terpyridine derivatives with extensive biochemical evaluation and structural analysis. Our results are described in detail in this poster.

USA and Postdoctoral studies from School of Medicine, University of Mississippi. He is the Professor of School of Medicine, Ewha Womans University, Korea. He has published more than 120 papers in reputed journals.

The function and the role of glucosylceramide have not been well studied in the central nervous system. This study was aimed to investigate the possible roles of glucosylceramide in memory function in aged mice. Glucosylceramide (50 mg/kg, p.o.) showed memory enhancing activity after 3-month treatment in the aged mice (C56BL/6, 18-20 month-old) through Y-maze, novel objective test and Morris water maze test. Long-term treatment of glucosylceramide decreased the expression of iNOS and COX-2 in the brain of aged mice. The LPS-induced mRNA level of iNOS, COX-2, IL-1 and TNF-was reduced by the acute treatment with glucosylceramide in adult mice. These results suggest that glucosylceramide plays an important role in anti-inflammatory and memory enhancement, and it could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

Inés María Díaz Hernández has completed her Pharmacy degree in 2014 at University of Salamanca. In 2014/2015 she is doing a master degree in Pharmacy and Pharmaceutical Technology at Complutense University of Madrid, with an experimental study entitled: “Development of Dexamethasone Nanocapsules in the Treatment of Leukemia”. The objective of this study is to prove the efficiency of the nanosystems in cell cultures.

Dexamethasone has demonstrated to be effective stimulating apoptosis in the treatment of lymphoblastic leukemias. Due to the resistances and side effects of this glucocorticoid the treatment is restricted and requires high dosages of the drug to be effective. A novel way of treatment is considered, formulating lipid nanocapsules loaded with dexamethasone, that will permit a controlled and selective release that decrease side effects, also facilitating their cell internalization avoiding resistance mechanisms. Lipid nanocapsules are formed of an oil nucleus compounds by Labrafac® in which the active ingredient is dissolved, surrounded by a phospholipid layer and external cover of a hydrophilic surfactant. Nanosystems are developed with phase inversion temperature method (PIT). Due to dexamethasone is not soluble in Labrafac®, a solubility study of the drug is carried out in a large numbers of organic solvents and oily vehicles, which result effectives: as organic solvent dimethyl sulfoxide (DMSO); and as oily vehicle: Capryol 90®. Two types of nanocapsules are obtained: (A) dissolving dexamethasone in DMSO before the other components incorporation, evaporating organic solvent because of temperature increasing during elaboration; and (B) dissolving dexamethasone in a mixture of Labrafac®: Capryol® (50:50). Both types of nanocapsules became effective for carrying dexamethasone and presented a half size of 50 nanometres with anunimodal distribution, even if with respect to nanocapsules (B) exists a 4 per cent of the population whose distribution is largest.

Gyu-Yong Song has completed his PhD from Chungnam National University and Postdoctoral studies from the Univiersity of Georgia. He is a Professor at College of Pharmacy, Chungnam National University and the leader of Chungnam National University’s LINC (Leaders in INdustry-university Cooperation) project group. He has published more than 30 papers in reputed journals and has registered more than 20 patents. He has performed a development of DMNQ derivatives, decursin derivatives, carbazole derivatives and flavon derivatives, related to Wnt signaling pathway, platelet aggregation, anti-aging and so on. He has carried out the processing of ginseng, such as black ginseng.

Ginseng leaves contain relatively large amount of ginsenosides as compared with ginseng roots. But these are almost discarded because of detection of residual agricultural pesticides. However, through extraction and isolation of ginseng leaves, we could secure lots of various standard-ginsenosides. Especially, ginsenoside-Re was obtained about 23g per 1kg of ginseng leaves. In this study, we performed to efficiently make rare ginsenoside-Rh4, -Rg6, -Rg4 and -Rk3 by using ginsenoside-Re. After ginsenoside-Re was added edible vinegar of pH 2.6, it was steamed at 140℃ under 0.16 Mpa for 2 h. The alteration of the steamed ginsenoside-Re was determined by HPLC analysis. It showed that ginsenoside-Re was perfectly disappeared and new ginsenoside-Rh4 was gained as major material. Also, it was gained a small quantity of ginsenoside-Rg6, -Rg4, -Rk3 and –(R/S)-Rh1. Four kinds of ginsenoisdes were isolated from the steamed ginsenoside-Re by chromatographic method and pure ginsenoside-Rh4, -Rg6, -Rg4 and -Rk3 were tested for anti-aging effects. As a results, it were identified that ginsenoside-Rh4 and -Rg6 significantly prevented wrinkle formation and the loss of collagen, fibers with increased type I collagen genes (COL1A1). Also, all of ginsenoside-Rh4, -Rg6, -Rg4 and -Rk3 showed anti-oxidant effect. In particular, ginsenoside-Rg4 exhibited the highest reactive oxygen species (ROS) scavenging activity on Raw 264.7. As shown these results, ginsenoside-Rh4, -Rg6, -Rg4 and -Rk3 can be new anti-aging agents in the cosmetic industry.

Rebeca Simancas Herbada has completed Pharmacy degree in 2014 at Complutense University of Madrid. In 2015 she finished a master degree in Pharmacy and Pharmaceutical Technology at the same University, with an experimental project (“Development of a hydrogel for oral administration”) supervised by Ana Isabel Torres Suarez and Ana Fernandez Carballido.

This work presents the synthesis of a poly (magnesium acrylate) hydrogel called PAMgA developed for oral drug delivery systems. The hydrogel synthesized had a concentration of 5 mM of cross-linker agent, ammonium persulfate (PSA) that confers long segments between linking points in the magnesium acrylate monomer (AMgA) chains. Budesonide is a corticosteroid with high glucocorticoid effect and weak mineralocorticoid effect, which provides antiinflamatory activity. It has low solubility in aqueous solutions because of its steroid structure. Tablets of PAMgA containing 9 mg of drug were elaborated. The swelling capacity and the percentage equilibrium water content (EWC) of PAMgA were determined by the gravimetric method; and the drug dissolution from tablets was evaluated using USP method 2. For all these assays three different media were used: distilled water, simulated gastric fluid at pH 1.2 (FaSSGF) and simulated intestinal fluid at pH 6.8 (FaSSIF), where 0.5% sodium lauryl sulfate (SLS) was used as surfactant in order to guarantee sink conditions. EWC obtained were higher at pH 6.8 (94.02 ± 0.03%) than at pH 1.2 (91.02 ± 0.05%) and than in water (88.94 ± 0.03%), probably due to the increase of the pH and the different ions that contains the media. Budesonide showed a lower dissolution rate from tablets at pH 6.8 although 100% of the drug was released after 24 hours in both media. These results make PAMgA hydrogel a good excipient for sustained drug delivery devices for oral administration.

Ana Isabel Fraguas Sánchez has completed her Pharmacy degree in 2012 at Complutense University of Madrid. In 2013 she finished a master degree in Pharmacy and Pharmaceutical Technology, with an experimental study entitled “Development of Cannabidiol Microparticles”. Currently, she is PhD student at Complutense University and she has published several papers related with cancer disease´s. She is the president of the Spanish chapter of American Association of Pharmaceutical Scientist (AAPS).

Cannabidiol (CBD) is the major nonpsychotropic cannabinoid presents in Cannabis sativa plant. It has proved to have a potential therapeutic utility in several kinds of tumors, due to its ability to inhibit or reduce the proliferation, adhesion, migration and invasion of cancer cells and to induce apoptotic effects. Breast cancer is one of the tumors where CBD has shown a high anticancer activity. However, despite its potential clinical interest it is difficult to develop an effective formulation with CBD because it has a low aqueous solubility and several stability problems. Systems as nanoparticles (Nps) may resolve these questions, and also may increase antitumor activity of cannabidiol. The aim of this work was to develop biodegradable nanospheres loaded with CBD for parenteral administration for the treatment of breast cancer. NPs were elaborated using poly-D, L-lactide-co-glycolide resomer (PLGA 502®) by nanoprecipitation technique and were characterized in terms of morphology, particle size, zeta potential, drug loading, entrapment efficiency and in vitro drug release. Formulations with 10% and 20% of CBD were prepared. Spherical, nonporous and uniform Nps were obtained, showing a particle size below 200 nm and a high drug loading and entrapment efficiency. The antitum

María Isabel Morales Calero has completed Pharmacy degree in 2014 at Sevilla University. In 2015, she has studied master degree of Pharmacy and Pharmaceutical Technology at the University Complutense of Madrid. The title of her experimental project is “In vitro release assays of controlled delivery systems”, supervised by Ana Isabel Torres Suárez.

Cannabidiol (CBD) is the main no-psychoactive component of Cannabis sativa, and the second most prevalent active component of this plant. Numerous studies have demonstrated the utility of CBD to treat many diseases such as cancer. Biodegradable microparticles are very interesting systems to get controlled and/or targeted drug release. Several polymers have being used to elaborate these delivery systems, such as poly-ε- caprolactone (PCL). The aim of this work was to evaluate the influence of the release medium composition on the CBD release from PCL microparticles for intramuscular administration. CBD-PCL microparticles were prepared by the emulsion-solvent evaporation method and were characterized in terms of size, by laser diffraction; shape and aggregation, by scanning electron microscopy; and loading and encapsulation efficiency of CBD, by HPLC. To evaluate the in vitro release of CBD from microparticles two different media were used: phosphate buffer, commonly used for these in vitro assays, and fluid simulated body (SBF), trying to represent the similar conditions that occur in vivo. The assay was carried out in a shaking water bath at 100 rpm and 37ºC during 20 days. Non-aggregated spherical microparticles were obtained with average size of 40 µm and encapsulation efficiency near 100%. In the release assay, an increase in the size of the microparticles in SBF was observed, while the size of microparticles in phosphate buffer decreased with time due to the release of CBD. However the release of CBD in phosphate buffer (87 %) was faster than the release in SBF (82 %) at 13 days.

In this study, the relationship between the alteration of electrolyte, especially potasium/sodium levels and the dose of diuretic antihypertensive drugs which were started to use in the hypertensive patients and they were followed and evaluated by cardiology clinics. Maintaining of the electrolyte level is important for the healthy functioning of the cardiovascular system. Statistical analysis of the clinical data was performed by SPSS 11.5 software. P value of < 0.05 were considered statistically significant. The age scale of 51 patients (27 female, 24 male) participated in the study was 29 and 77 (calculated %53.67± 11.2). The percentage of patients with ≥1 year is % 29.4, whereas the percentage of the patients with hypertension period < 1year is %70.6. During the monitoring, % 52.8 of patients has taken % ACEI + diuretic, %31.4 has taken ARB + diuretic, %4 has taken the combined + calcium channel blocker and % 2 has taken combined + beta-blockers theraphy. When the effect depends on the dose of diuretic used in the treatment was examined and compared, K value has showed a tendency of fall close to the border area, in patients taking 25 mg hydrochlorothiazide. However, no significant difference has been determined (p = 0.081). In the patients, even though there was a slope of hypokalemia with rising the dose of HCTZ, this has not reached statistically the significant value. Resulting from the findings, antihypertensive combinations including diuretics could be used safely in a short period of treatment. It should still be considered that the electrolyte imbalance may occur with increasing doses of diuretics. This is important and should be taken into the account in terms of treatment safety.

P Marcianes Moreno has finished her Pharmacy degree in 2012 at Complutense University of Madrid. In 2013 she completed a master degree in Pharmacy and Pharmaceutical Technology, with a research study entitled “Elaboration of Tolcapone Nanoparticles”. Currently, she is a PhD student at Complutense University.

Tuberculosis (TB) is a highly contagious persistent infection caused by M. Tuberculosis, which has higher mortality rate than any other infectious diseases. According to the WHO one-third of the population is infected and 1.8 millions of people die every year. TB appears mainly in the lungs but can also develop as extra pulmonary tuberculosis in the central nervous system (CNS). The control of resistant TB represents an important challenge, so it has showed that quinolones family such as Gatifloxacin (GAT) is an alternative treatment for resistant TB. However, this drug is low lipophilic which makes it difficult to cross the BBB. Nanocarriers can cross biological barriers like blood-brain barrier (BBB) and are a new strategy in treating TB to hydro soluble compound as GAT. The aim of our study was developed biodegradable GAT-loaded PLGA-labrafil nanoparticles (NPs) and study their transport through the BBB. NPs were prepared using poly D, L-lactic-co-glycolic acid Resomer (PLGA 502®) and prepared by nano precipitation technique. Particles were characterized by SEM, encapsulation efficacy and in vitro release at pH 7.4. SEM revealed that NPs were spherical and with smooth surfaces. Mean particles sizes were around of 189 nm and an encapsulation efficiency of 15%. Cerebral cortex images showed a marked increase of fluorescence when the surfactant-coated NPs were administered to rats. These results suggest that the formulations are adequate systems to access into the brain.

Young-Kyoon Kim PhD is currently a Professor at department of forest products & biotechnology in Kookmin University, Seoul, Republic of Korea.

Acanthopanax sessiliflorus, is a smaller woody shrub and has traditionally been referred to have anticancer activity, but it has not been scientifically explored so far. Therefore the present study was aimed to elucidate the anticancer effect of Acanthopanax sessiliflorus stem bark extracts (ASSBE). The stem barks was extracted in methanol and then fractionated with hexane, butanol and water. Cytotoxicity of these fractions against MDA-MB-231 and MCF-7 human breast cancer cells was determined by MTT colorimetric assay. The hexane fraction of ASSBE showed greater activity towards both the human breast cancer cells compared to other two fractions at a minimal concentration of 50 µg/ml. Hence, we were further investigated the effects of this bioactive fraction, n-hexane (ASSBE-nHF) on breast cancer cells. ASSBE-nHF significantly reduced the proliferation of breast cancer cells assessed by counting cell numbers after 72 h treatment using hemocytometer. The Annexin V-FITC/PI, Hoechst 33342 staining, DNA fragmentation assays and immunoblotting of apoptosis markers like caspases showed ASSBE-nHF induces necrosis like cell death in MCF-7 and MDA-MB-231 cells. Further, ASSBE-nHF significantly increased the production of ROS and decreased the mitochondrial membrane potential (MMP) in MCF-7 cells. Similarly, it decreased the MMP in MDA-MB-231 cells, but had no effect on ROS production. The cytotoxic effect of ASSBE-nHF in MCF-7 cells was not significantly reversed even in the presence of n-acetylcysteine, an antioxidant. Moreover, ASSBE-nHF significantly decreased the levels of caspase 3, caspase 7, caspase 9, caspase 8, cyclin D1 and including the house keeping protein GAPDH represents the inhibition of protein synthesis in human breast cancer cells. Since, necrotic dying cells retain the process of protein synthesis, Acanthopanax sessiliflorus stem bark extracts induced cytotoxic effects in human breast cancer cells might be through endoplasmic reticulum stress response. In conclusion, the present findings provide evidence that ASSBE-nHF induces non-apoptotic cell death in human breast cancer cells via both ROS dependent and independent pathways associated with mitochondrial membrane depolarization.

Oh Won Keun has completed his PhD as studies about natural products chemistry from Korea Advanced Institute of Science and Technology (KAIST) and Postdoctoral studies from Baylor College of Medicine, USA. He works as Associate Professor at College of Pharmacy in Seoul National University, Korea. He has published more than 115 SCI (E) papers in reputed journals and has been serving as the director of Korea Bioactive Natural Material Bank (KBNMB) and also as an Associate Editor in Natural Product Sciences (NPS).

Bioassay-guided fractionation of Camellia japonica led to the isolation of six new 3,4-seco-28-noroleanane triterpenoids, 4,7, 17, 29-tetrahydroxy-16-oxo-3, 4-seco-28-norolean-12-en-3-oic acid (1) 4,7, 17, 29-tetrahydroxy-16-oxo-3, 4-seco-28-norolean-12-en-3-oic acid methyl ester (2) 4,7, 17-trihydroxy-16-oxo-3, 4-seco-28-norolean-12-en-3-oic acid n-butyl ester (3) 4,17, 29-trihydroxy-16-oxo-3, 4-seco-28-norolean-12-en-3-oic acid methyl ester (4) 4,17, 29-trihydroxy-16-oxo-3, 4-seco-28-norolean-12-en-3-oic acid n-butyl ester (5) and 17, 29-dihydroxy-16-oxo-3, 4-seco-28-norolean-4 (23), 12-dien-3-oic acid (6) and all of their molecular structures were elucidated by means of extensive spectrocopic analysis, including HRMS and 1D- and 2D-NMR data. In a rotenone model of Parkinson’ disease (PD), compounds 36 showed potential neuroprotective effects on SH-SY5Y neuronal cells. Specially, compound 5 showed the strongest protective effects, and Real time PCR and Western blot data revealed that this function may be related with its inhibitory effects on -synuclein aggregates. This study indicated a new class of chemical entities for developing bioactive compounds for PD treatment.

Kyong-Hwa Kang PhD is presently working as a Research Professor at Department of Marine Bio Convergence Science and Marine Bioprocess Research Center (MBPRC) at Pukyong National University, Busan, South Korea. She received her PhD from Pukyong National University in 2011, and conducted her postdoctoral studies at the same Laboratory. Her major research interests are investigation and isolation of protein and peptides from mainly marine microalgae and other marine sources.

The aim of this study was to investigate antihypertensive effect of bioactive peptides from skate (Okamejei kenojei) skin gelatin. The Alcalase/protease gelatin hydrolysate below 1 kDa (SAP) exhibited the highest angiotensin-I converting enzyme (ACE) inhibition compared to other hydrolysates. SAP can decrease systolic blood pressure significantly in spontaneously hypertensive rats. SAP inhibited vasoconstriction via PPAR-c expression, activation and phosphorylation of eNOS in lungs. Moreover, the expression levels of endothelin-1, RhoA, a-smooth muscle actin, cleaved caspase 3 and MAPK were decreased by SAP in lungs. Vascularity, muscularization and cellular proliferation in lungs were detected by immunohistochemical staining. Finally, two purified peptides (LGPLGHQ, 720 Da and MVGSAPGVL, 829 Da) showed potent ACE inhibition with IC50 values of 4.22 and 3.09 lM, respectively. These results indicate that bioactive peptides isolated from skate skin gelatin may serve as candidates against hypertension and could be used as functional food ingredients.

Kinetics of oxidation of [CrIII(CD)(H2O)52+] (CD = Carbidopa) with N-bromosuccinimide (NBS), was studied in an aqueous solution over ranges of complex and NBS concentrations of (1.0-5.0) ×10-4 mol dm-3and (0.5-5.0) × 10-2 mol dm-3, respectively, (0.2 - 0.3) mol dm-3 Ionic strength and (30 - 50)oC. The product of oxidation was examined using High Performance Liquid Chromatography (HPLC) technique, reversed-phase partition mode. The reaction is first-order with respect to [CrIII(CD)(H2O)52+] and [NBS]. The reaction rate increases with increasing pH values over the range studied. Thermodynamic activation parameters were calculated. Oxidation of [CrIII(CD)(H2O)5+2] by [NBS] found to obey the rate law d[CrVI]/dt = d [CrVI]/d t = {k5[MnII] + (k4 + k3/[H+])[NBS]}×[CrIII(CD)(H2O)5] . It is assumed that one step two- electron transfer takes place via an inner-sphere mechanism. A common mechanism for this reaction is proposed. With patients who administer Anti-Parkinson drug (CD), formation of [CrIII(CD)(H2O)5+2] in vivo can be expected due to CrIII is taken as a natural food element. So, this work provides an opportunity to identify the nature of such interactions in vivo similar as in vitro.

Orhan CORUM is a research assistant at University of Selcuk. He is still PhD student in the pharmacology department. He won scholarship at veterinary college of Dicle University. His Paste yo ur Logo here interest is cancer, pharmacokinetics and diabetes. Nowadays he is mostly cancer molecular studies.

Tulathromycin is widely used as extralabel in sheep, whereas there has no any data about safety in sheep. The aim of this research was to determine the safety of tulathromycin in sheep. In this research, single dose of 2.5 mg/kg tulathromycin was administered subcutaneously (SC) to 10 male yearling Merino sheep. Blood samples were obtained before (0. day, control) and after at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8 and 9 days. Hemogram values (White blood cell, red blood cell, platelet, hemoglobin, hematocrit), and cardiac (Troponin I, creatine kinase-MB mass), hepatic (Alkaline phosphatase, total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin) and renal (Blood urea nitrogen, creatinine) damage markers were determined from blood samples. There were no any clinical changes observed in sheep during experimental period. Increased troponin I level was determined (P<0.05) at 1st day, while decreased red blood cell counts, hemoglobin and hematocrit levels were measured at 6th day when compared to control (0. day) values. Statistically significance changes (P<0.05) were determined within reference range in hepatic (Total bilirubin, alanine aminotransfrerase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin) and renal (Blood urea nitrogen, creatinine) damage markers. In conclusion, tulatromycin may cause transient increase in the cardiac damage markers and changes in the blood picture. However, it is stated that single dose (2.5 mg/kg, SC) of tulatromisin may safe in sheep. Keywords: Sheep, tulathromycin, safety

Thioacetamide (TAA) administration is an established technique for generating rat model of liver damage. The aim of this study was to investigate the potential hepatoprotective effect of the ethanol extracts of the aerial parts of Allium paniculatum L. (A. paniculatum) and Capparis spinosa L. (C. spinosa) in experimental liver damage induced by TAA in rats. Forty two adult male Wistar rats were divided into seven groups. Rats of the 1st (normal control) and 2nd (TAA-intoxicated control) groups received the vehicle (1 mL/kg). Animals of the 3rd group (reference) received silymarin (50 mg/kg). The 4th to the 7th groups were treated with A. paniculatum and C. spinosa extracts (200 and 400 mg/kg, respectively). Rats were administered the vehicle, silymarin or extracts orally for 21 days and simultaneously administered TAA (except the 1st group) at subcutaneous dose of 50 mg/kg, 1h after the respective assigned treatments every 72 h. At the end of the experimental period, animals were sacrificed by cervical decapitation, blood samples were collected for biochemical assessment. Livers were dissected out for determination of their antioxidant status and for histopathological examination. Injection of TAA significantly elevated serum levels of ALT, AST, ALP and γ-GT and total bilirubin in hepatotoxic group compared to normal controls. In the liver, significantly elevated level of malondialdehyde (MDA), lowered levels of reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were observed in TAA-hepatotoxic group. Treatment of rats with A. paniculatum or C. spinosa displayed hepatoprotective effect in a dose dependent manner as evident by reduced levels of serum ALT, AST, ALP, γ-GT, BRN and hepatic MDA concentration, as well as higher CAT, GPx, SOD activities and GSH concentration compared to TAA-hepatotoxic controls. In conclusion, A. paniculatum and C. spinosa extracts attenuate hepatotoxicity induced by TAA. Keywords: Allium paniculatum, Capparis spinosa, thioacetamide Hepatoprotective, Hepatotoxicity.

Objective and Design: The purpose of this study was to evaluate the anti inflammatory, anti-arthritic and analgesic effects of antidepressants. Methods: Carrageenan model was used to assess effect on acute inflammation. Paw volume were measured at 1, 2, 3 and 4th hour post challenge. Anti-nociceptive effect was evaluated by hot plate method. Chronic inflammation was developed using Complete Freund's Adjuvant (CFA). The animals were injected with Freund’s adjuvant in sub-plantar tissue of the right posterior paw. Paw volume, ankle flexion scores, adjuvant-induced hyperalgesia and serum cytokine levels were assessed. Results: Results obtained demonstrate that mirtazapine, venalfaxine and escitalopram significantly and dose-dependently inhibited carrageenan-induced rat paw oedema. Mirtazapine, venalfaxine and escitalopram increased the reaction time of rats in hot plate test. We observed an increase in paw volume, ankle flexion scores, thermal hyperalgesia, serum levels of interleukin-1β, PGE2 and TNF-α, induced by intraplantar CFA injection. Regular treatment up to 28 days of adjuvant-induced arthritic rats with mirtazapine, venalfaxine and escitalopram showed anti anti-inflammatory and analgesic activities by suppressing the paw volume, recovering the paw withdrawal latency, and by inhibiting the ankle flexion scores in CFA-induced rats. In addition significant reduction in serum levels of interleukin-1β, PGE2 and TNF-α level in arthritic rats was reduced by treatment with drugs. Conclusion: These results suggest that antidepressants have significant anti-inflammatory and anti-nociceptive effects in acute and chronic models in rats, which may be associated with the reduction of interleukin-1β, PGE2 and TNF-α levels.

Burak DiK is pursuing his PhD education from Selcuk University and he will complete PhD education in this year. He works as Researcher Assistant in Selcuk University, Faculty of Veterinary Medicine. He has published more than 13 papers in reputed journals and he has been working some repute project.

The aim of this research was to determine the effect of Corynebacterium cutis lysate on cytokine levels including hemogram parameters in sheep. In the research, 10 male yearling Merino sheep was used. Recommended dose (8 mg, 0.4 mL) of Corynebacterium cutis lysate (Ultra-corn® Inj.) was administered subcutaneously at a single dose to each animal. Before (0 hour, control) and after the treatment, blood samples were obtained from v. jugularis at 2, 4, 8, 12, 24, 48, 72 and 96 hours. Concentrations of serum tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, IL-6 and IL-10 were measured with ELISA reader, while hemogram values (white blood cell, red blood cell, platelet, hematocrit, hemoglobin) were determined with hemocell counter. Corynebacterium cutis lysate caused fluctuations on the cytokine levels (P>0.05) and did no effect the hemogram parameters. In conclusion, it may be stated that treatment of Corynebacterium cutis lysate has no statistically significance effect on the cytokine levels, and detailed researches are need to determine the effect of Corynebacterium cutis lysate on the passive immunity.

The influence of agilent C18 stationary phases on the separation of ibuprofen, naproxen and ketoprofen compounds with a water rich mobile phase over high temperature has been critically investigated. The van’t Hoff relationships between the retention factors and reciprocal temperature were found to depend on the range of temperature used. The thermodynamic parameters of the separation step were calculated. Different parameters as flow rate, types of organic modifier, injection volume and types of buffer investigated. The method was suitably validated and successfully applied to the determination of ketoprofen, naproxen, and ibuprofen in several analgesic/antiphlogistic pharmaceutical formulations. The method has been validated according to accuracy, precision, specificity and linearity and reproducibility

Juan Aparicio-Blanco is a PhD student graduated in Pharmacy at Complutense University (Madrid) with Best Academic Record Award at the Faculty of Pharmacy and specialized afterwards in the field of Pharmaceutical Technology. He is a Researcher in the project “Design of novel brain-targeted anticancer-loaded nanocarriers to handle most troublesome brain tumors” at the Pharmaceutical Technology Department. He is the Researcher in Institute of Industrial Pharmacy, Complutense University of Madrid, Spain. His Pre-doctoral fellow is granted by the Spanish Ministry of Education and Culture (FPU13/02325).

Since recently, many authors in the field of nanomedicine seem to have put the focus on lipid nanocapsules (LNC), nanocarriers consisting of an oily core provided with a surfactant shell. Both their nanometric size and their lipophilic nature may potentially play a key role to enable intravenous administration of lipophilic drug substances. Given the fact that intravenous administration allows release times to be prolonged much longer than with oral administration, the goal to be pursued by means of the present study is to evaluate the aptness of these novel nanocarriers to extend drug release over time, taking cannabidiol (CBD), the main non-psychotropic cannabinoid, as a model of lipophilic drug substance to encapsulate. To that aim, 50 nm-sized CBD-loaded LNCs were developed according to an expanded phase inversion method. Thermo stability of the drug substance under the heating conditions required by the mentioned solvent-free technique and the encapsulation efficiency of the drug-loaded nanocarriers were determined. So as to test the feasibility of LNC to serve as controlled drug delivery systems of CBD, in vitro release kinetics assays were performed by a dialysis method, since no centrifugation procedure has proven to date successful in separating nanoparticles from an aqueous medium. Phosphate buffer solution pH 7.4 added with polysorbate 80 was chosen as release medium in order to mimic physiological conditions with the highest accuracy and to ensure sink conditions by enhancing CBD solubility in water. Our results revealed that LNC efficiently extend CBD release at least over fifteen days under the assayed conditions.

Irmak DiK commenced her PhD from Selcuk University and she will complete it in the next year. She works as a researcher assistant in Selcuk University, Faculty of Veterinary Medicine. She has published more than 8 papers in reputed journals and she has been working on some project.

Chemical extract of Nerium oleander (NO) is identified as in vitro antibacterial and antifungal, while there is not any study about antiviral effect of NO. The aim of this study was to evaluate in vitro effect of NO distillate (NOD) on different viruses [(Bovine Herpesvirus-1 (BHV-1), Herpes Simplex Virus-1 (HSV-1), and Bovine Adenovirus-1 (BAV-1)]. Lyophilized NOD was dissolved at concentration of 10mg/mL with distillated water and filtered. Vero and MDBK cells were grown at 37ºC in DMEM containing 10% FCS, 10mg/mL of streptomycin, 10000IU/mL penicillin G, nystatin 1250 IU/mL. 50µL of NOD was treated with 50µL 100 TCID50 diluted BHV-1, HSV-1 and BAV-1 in 96-well plates. After treatments, Vero and MDBK cells (3x105/mL) were added to wells at 4th, 8th, 12th, 24th and 36th, respectively. Other wells were evaluated as cell control (CC), virus control (VC) and NOD control. Plate was incubated in 5% CO2 incubator at 72h after cells were seeded. All wells were examined daily on an inverted microscope. In NOD control and CC were not observed any CPE, whereas CPE was determined in all of BHV-1, HSV-1, and BAV-1 controls. In conclusion, it may be stated that NOD has antiviral activity to BHV-1 and BAV-1. Although NOD has no antiviral activity against to HSV-1 with this method, methalonic extract of Neriumindicum has antiviral activity against to herpes simplex viruses. However, different viruses or methods should be investigated for determine antiviral effect of NOD.

Jeong Hill Park has completed his PhD from Seoul National University, Korea. He is the Professor of College of Pharmacy, SNU. He has published more than 230 papers and 30 patents

Jeong Hill Park has completed his PhD from Seoul National University, Korea. He is the Professor of College of Pharmacy, SNU. He has published more than 230 papers and 30 patents

A K Güliz has completed her Msc studies from Ege University Faculty of Science Biochemistry Department and initiated her PhD studies in 2010 in the same department. She has been working as a research assistant in Ege University Faculty of Science Biochemistry Department since 2010 and also as a researcher in Ege University Pharmacokinetic Drug Development & Research Center (ARGEFAR) Biosimilar Products Department Proteomics Unit since 2013. She is a funded researcher in two projects about nanoparticular anticancer agent researches.

In the last two decades, a number of nanoparticle-based therapeutic agents have been developed for the treatment of cancer. These nanoscale agents may provide more effective and/or more convenient routes of administration, lower therapeutic toxicity, extend the product life cycle and ultimately reduce health care costs. Folate-targeted drug delivery has become an alternative therapy for the treatment of various cancers, especially ovarian cancer. Folate receptors are known to be responsible for cellular accumulation of folate and folate analogs with high binding affinity. The anthracycline antibiotic doxorubicin has a broad spectrum of antineoplastic action and a correspondingly widespread degree of clinical use. Magnetic nanoparticles are being of great interest due to their unique purposes. For magnetic targeting, magnetic nanoparticle introduced first in the body and then under the influence of external magnets, it is possible to guide nanoparticles to a particular targeted site. Red blood cells derived vesicles maintains the material biocompatibility and preserves the complex protein makeup of RBCs essential for their bio-functionalities. The aim of work is to develop biocompatible nanoparticulate system that can be controlled by the external magnetic field and can be targeted via folate ligand in order to reach ovarian cancer. Red blood cells were used for biocompatibility of glucose/gluconic acid coated and doxorubicin loaded magnetic nanoparticles. In addition folate ligand was linked to the nanoparticulate system. That nanoparticulate system can be effective potential doxorubicin carrier for targeted ovarian cancer therapy.

Acknowledgement
We would like to thank for financial support received from The Scientific and Technological Research Council of Turkey (Project ID: 113Z165).

Habibe Yilmaz has completed her Msc studies in 2012 from Ege University Faculty of Science Biochemistry Deparment and initiated her PhD studies in 2012 in the same department. She is also started to work in Helvacızade Food, Drug and Chemistry Company as a researcher in AR&GE and Product Development Department in April 2013. At the same time, she also started to work in Ege University Pharmacokinetic Drug Development & Research Center (ARGEFAR) as a researcher in Biosimilar Products Department Proteomics Unit. She is a funded researcher in two projects about nanoparticular anticancer agent researches.

Last international statistics stated that the number of cancer patients will be more that 15 million in 2020. Depending on the location and the stages, most cancer types can be treated with applications such as surgery, radiotherapy and chemotherapy. Pharmacologically active anticancer drugs reach to tumor tissue with low specificity and dose-dependent toxicity in chemotherapy applications. These methods have some disadvantages. An anthracycline antibiotic doxorubicin which has a wide range of usage is administers to patients intravenously either alone or in combination with other drugs. It is used for treatment of breast, ovary, bladder, bronchiogenic lung, thyroid, gastric cancer, soft tissue, osteogenic and Kaposi’s sarcoma, neuroblastoma, Wilm’s tumor, Hodgin and non-Hodgin lymphoma, acute lymphoblastic and acute myeloblastic leukemia. Doxorubicin has many side effects such as cardiotoxicity and myelo suppression, it leads to a very narrow therapeutic index of the drug. Another important issue is unwanted drug resistance as well as these effects. At the present time, by using nanoparticular drug delivery systems, it is possible to reach lower dose of drug usage and making less harmful. Under this project, primarily, α-D-glucose coated iron oxide nanoparticles were synthesized. Doxorubicin was loaded to prepared glucose coated magnetic iron oxide nanoparticles via hydrazone bond. At this stage of the formulation, obtained product will have potential for concentrating in the desired site with an external magnetic field.

Acknowledgment:
We would like to thank for financial support received from The Scientific and Technological Research Council of Turkey (Project ID: 113Z165).

Åženay ÅanlÄer has completed her PhD in 2000 at Ege University Faculty of Science Biochemistry Department on Encapsulation of enzyme systems in erythrocytes. In 2007, she was appointed as an Assistant Professor and in 2013 she was appointed as a Professor at Ege University Faculty of Science Biochemistry Department. She is also a consultant in Ege University Pharmacokinetic Drug Development & Research Center (ARGEFAR) since 2013. Her main research interests are nanoparticular drug delivery systems for cancer therapy, proteomics, enzymology and drug design

Pharmacologically active anticancer drugs reach to tumor tissue with low specificity and they have dose-dependent toxicity in chemotherapy applications. Classical drug administration routes are oral and intravenous. Orally taken tablets or capsules result in irregular pharmacokinetic due to the metabolic pathways and they frequently damage healthy tissues due to low specificity. After the developments in nanotechnology, it is possible reduce these harmful side effects by using nano particular drug delivery systems. When iron oxide (magnetite) nanoparticles are loaded with some anticancer drugs, the drug loaded iron oxide nano particles can be directed to tumor tissues via an external magnetic field and this may mostly eliminate the side effects of classical oral treatment. In the present study, we computationally investigate interactions of Fe3O4 (magnetite) surface with pemetrexed and pazopanib drug molecules that are both separately conjugated with small specifically designed peptide link. In particular, we present thermodynamic, geometrical and electronic properties of the drug-peptide complex interacting with model Fe3O4 surface predicted by several molecular modelling methods (including semi empirical methods and DFT).

Acknowledgement:
We would like to thank for financial support received from The Scientific and Technological Research Council of Turkey (Project ID: 213M672).

Yeliz Yildirim has completed her PhD studies in 2009 from Ege University Faculty of Science Physical Chemistry Department. She is an Associate Professor since 2014 from Ege University Faculty of Science Chemistry Department. At the same time, she also started to working in Ege University Pharmacokinetic Drug Development & Research Center (ARGEFAR) as a researcher in Imaging Department Pre-phase Unit.

Lung cancer rate is still 12.8% of all cancers in the world, and cause of 17.8% of all cancer deaths'. Cancer is the beginning uncontrolled cell division. For the emergence of cancer, tumor cells must gain other malignant properties as well as invasion and metastasis. For this purpose, cancer cells use matrix metalloproteinases to surpass the barrier that contains extracellular matrix elements. Pemetrexed is a common drug used in combination with cisplatin and it is known that it has oodless side effects as the other anti cancer agents. It has many side effects such as changes in blood cell counts, diarrhea, vomiting, pain, redness, swelling or sores in the mouth, nausea, decreased appetite, fatigue, skin rashes, hair loss, constipation, loss of sensation, kidney failure and liver test abnormalities. Pazopanib is a new generation anti cancer drug and, many phase studies have been found in clinical trial for the treatment of lung cancer screening, especially in combination with numerous drugs. Pemetrexed is also one of the drugs that are investigated in the use combination with pazopanib. Therefore, pazopanib and pemetrexed have been selected under the project. Under this project, at the first step magnetite nanoparticles functionalized with active amine groups. At the same time, anticancer agents were covalently bonded to a specifically designed peptide which is a substrate of a selected matrix metalloproteinase. In the final stage we attached peptide-drug conjugates to magnetic nanoparticles via amide bond.

Acknowledgement:
We would like to thank for financial support received from The Scientific and Technological Research Council of Turkey (Project ID: 213M672).

Sathish Amirthalingam, BPharm, MPharm, PhD, PGDHM, is a clinical pharmacist from India and currently working in International Medical University, Malaysia. He was a state first and distinction research scholar in Post-Graduation level. He has a teaching and professional experience of 13 years in the field of pharmacy. He received 6 awards from various bodies from pharmacy fields including state and national levels for best research paper and research project. He had written 2 books in pharmacy field like clinical pharmacy and pathophysiology for pharmacy students. He has published 21 national and international papers, 2 copyright of his innovative clinical software and he has presented 18 papers in national and international conferences. He has guided 4 under graduate, 8 post graduate projects and he is guiding 4 more under graduate projects currently. He also associated with life member in various professional bodies like IPA, IHPA and he was a member of board of studies in Dept. of pharmacology, S.P.University.

Topical antibacterial drugs are generally used to treat superficial bacterial infections. In Malaysia, topical antibacterial drugs are mostly available as over-the-counter (OTC) products that enable the patients to gain access easily. Since indiscriminate use of topical antibacterial drugs had been recognized as a factor to drive antibacterial resistances, the roles of community pharmacists (CPs) are vital to ensure the appropriate use of these medications. Therefore, this study was conducted to assess the perceptions and experiences of CPs in Kedah state, Malaysia on the dispensing of topical antibacterial drugs. A cross-sectional study involving a pre-validated questionnaire was conducted in community pharmacies within Kedah state, Malaysia. 53.4% of CPs in Kedah state perceived that topical antibacterial is not necessary for every topical bacterial infection. Patients’ information gathering and patient counselling were agreed to be important. Fusidic acid was the most frequently dispensed topical antibacterial drug while superficial wound was reported to be the most frequently encountered topical bacterial infection. 12.60% of CPs encountered antibacterial resistance cases but none of them reported. The drug that was having resistance issue was identified to be Neomycin. CPs in Kedah state generally had the right perceptions on the dispensing of topical antibacterial drugs. However, their knowledge on the rational use of topical antibacterial drugs and vigilance on the antibacterial resistance issue should be improved. Nevertheless, vigilance of CPs on antibacterial resistance issue was low. Thus, more training and educational programmes should be implemented to promote rational antibiotic use and improve CPs’ vigilances on antibacterial resistance issues

Raoufa A I Abdel Rahman has completed her PhD in 2003 at Alexandria University, Faculty of Agriculture, Genetics Dep., throught a collaborative scholarship with University of Georgia, Athens, USA. She completed a research project entitled "Exploring IRES mediated discistrons for the phytoremediation of Mercury". Currently, she is the director of Pharmaceutical Bio-products Research Dep., City of Scientific Research and Technology Applications, Alex., Egypt. Her main research interests are using plant tissue culture and genetic engineering techniques to conserve rare and endangered plant species, as well as enhancement the productivity of important pharmaceutical compounds from plants. She is working in several projects dealing with the production of antiviral, anticancer, and antioxidant compounds from plants using in-vitro cultures.

Over the past three decades, plant cell and tissue culture and plant biotechnology techniques have proved to be a valuable tool for study biosynthesis and production of plant secondary products. Rosmarinic acid (RA) is a natural phenolic compound produced by variety species of Lamiaceae and Boraginaceae families. In the recent few years, RA has attracted attention due to its antiviral, antibacterial, anti-inflammatory and anti-allergic activities. In the present study, the efficiency of using plant tissue culture techniques as a promising alternative method for the production of RA from basil and lemon balm was tested. Callus and shoot cultures were established using different types of explants and medium composition to test the optimum condition for their production. Results showed that leaf explants were the best explants for callus production. MS medium containing 1mg/l BA and 1mg/NAA (MS2) was the best medium for callus growth in lemon balm while MS4 was the optimum media for basil. Stem segments and shoot tips were used as explants for production of shoot cultures in lemon balm and basil. RA levels were determined in control, callus and shoot cultures. Results showed that callus and shoot cultures accumulated higher levels of RA compared to control. RA levels ranged from 9.42±1.27 to 38.25±0.73 ug/mg plant dry weight. Shoots produced 3 and 2.7 folds higher rosmarinic acid levels compared to control in lemon balm and basil. The overall results indicated that plant tissue culture is an efficient tool for RA production from basil and lemon balm plants.

Clematis flammula is a plant widely used in traditional medicine in Algeria to treat gout and various inflammatory disorders. Hyperuricemia and gout are classically treated by drugs such as febuxostat and allopurinol that favour the elimination or degradation of uric acid (UA) through the inhibition of xanthine oxidase (XO). However, these synthetic drugs could cause adverse side effects which instigated researchers to seek alternative plant-derived molecules. In this perspective, hypouricemic activities of ethanol and aqueous phase of ethyl acetate leaf extracts of C. flammula were examined in oxonate-treated mice. Male mice were randomized into 10 groups (n=6), 5 were administered extract only and 5 rendered hyperuricemic with an intraperitoneal injection of oxonate (oxo) (250 mg/kg). The latter inhibits uricase, an enzyme that catalyses the conversion of uric acid to allantoine. The hyperuricemic groups were administered orally carboxymethyl cellulose (CMC) at (0.8%), extracts (100, 200 and 400 mg/kg) and allopurinol respectively, one hour after they received oxo. CMC (0.8%) is considered to be the vehicle in which extracts and allopurinol (10 mg/kg) were dissolved. The duration of the treatment was three days at the end of which the mice were scarified. Blood was collected for serum analysis of uric acid content and livers were excised to determine XO/XDH activity. A significant reduction of uric acid in mice treated with C. flammula extracts was observed, from 4.50±0.19 mg/dl in hyperuricemic non-treated mice to 0.69±0.06, 0.69±0.06 and 1.39±0.18 mg/dl in the hyperuricemic groups pre-treated respectively with 100, 200 and 400 mg/kg of ethanolic extract. The hypouricemic effect of the aqueous phase of ethyl acetate was more prominent leading to a higher reduction of uric acid leading to 1.29±0.22, 1.29±0.16, 1.76±0.3 mg/dl in hyperuricemic mice treated with 100, 200 and 400 mg/kg of the extract, respectively. Allopurinol, on the other hand, reduced uric acid level to 0.33±0.02 mg/dl. Regarding XO/XDH activity in the liver of oxonate-treated mice, no inhibition of that activity was noticed for those groups fed with the ethanolic extract. However, a strong inhibition on hepatic XO was exerted by aqueous of ethyl acetate by 68.84%. 74.46, 71.95 and 73.16% at 100, 200 and 400 mg/kg respectively, while its percentage inhibitions on XDH were of 61.15, 70.31 and 62.07% suggesting that the extract’s hypouricemic effect might be related to enzyme inhibition. Allopurinol, on the other hand showed a higher inhibition of xanthine oxidase than the extract (80.54 and 77.61% on XO and XDH respectively).

Pseudomonas aeruginosa is a pathogen commonly present in the lungs of patients with chronic airway infection in cystic fibrosis (CF). Pseudomonas aeruginosa produces proteins called proteases that are associated with virulence and disease progression. These proteases were recently shown to recognize and specifically cleave peptides comprising three glycines (3xGly). We believe that this feature can be used to facilitate the specific site-specific delivery of theraupetic agents to the lungs of CF patients. More specifically, nanoparticles capped with 3xGly peptides will release the loaded content only upon proteolytic activity of P. aeruginosa present in the lungs thus providing site specific release of the drug. Furthermore, we have studied the potential of nanoparticles for delivery of antibacterials to Gram-negatives to eradicate P. aeruginosa infection in in vitro models for host-pathogen interactions in the lungs.

The Wnt/β-catenin signaling pathway is associated with the development of embryos and regulates the proliferation and differentiation of cells. Abnormal activity of this pathway and the growth of β-catenin-dependant transcription induce various tumors development including colon and prostate cancer. In this study, it were synthesized the (+)-decursin derivatives originating from decursin, isolated from Angelica gigas, and screened in a cell-based assay for detection of relative Luciferase reporter activity. As a result, decursin derivative (8b), introduced substituent of 3-acetoxy cinnamoyl group, showed the most potent inhibitory activity (97.0%) for Wnt/β-catenin pathway. In structure activity relationship (SAR), it shows that double bond, included in cinnamoyl group of decursin derivatives, is necessary for of Wnt/β-catenin pathway. Also inhibitory activities are most effective, when functional groups locate ortho- or meta-positions, substituted on benzene ring of cinnamoyl group. In HEK293 reporter cells, it was revealed that 8b inhibited dose-dependently CRT induced by Wnt3a (IC50 = 9.85 M) and decreased of intracellular β-catenin’s protein level. Also, 8b decreased dose-dependently cytosolic β-catenin’s protein level in PC3 prostate cancer cell. And it acted as promoter of the degradation of β-catenin and suppressed the expression of Cyclin D1 and c-myc, which are downstream target genes of β-catenin. As shown these results, compound 8b may lead to candidate of new anti-tumor agents for prostate cancer.

Jong-Hoon Kim has completed his PhD from Konkuk University. He is the Associated Professor in Chonbuk National Univeristy, Republic of Korea. He has published more than 70 papers in reputed journals and has been serving as an Associated Editor of Journal of Ginseng Research.

The objective of our present research was to identify the novel therapeutic target for diabetic cardiomyopathy. To achieve this level of identifications we try to inspect the genes related to metabolism and its crucial title role in the cardiac functions during diabetes. In this study, via microarray analysis we observed the significant rises of metabolic gene expression such as acyl-CoA thioesterase 1 level in the myocardia of db/db mice when compared to normal group of animals. Consequently, gain-of-function and loss-of-function approaches in db/db mice were studied via acyl-CoA thioesterase 1 gene expression level in cardiac functions. Present investigations also exemplify the significant anti-diabetic potential of ginseng total saponin (GTS). Though, the multifaceted connection between the anti-diabetic effects of Korean red ginseng (KRG) and its sound effects on the level of metabolic gene expression on anti-diabetic animal’s heart has not identified. Henceforth, in current research we attempt to assess the link between the anti-diabetic effects of KRG and the level of metabolic gene expression profiles in the heart of db/db mice. Apoptosis-related genes including Cideb, Bdnf, Myc, Cd74, Inhbb, Lcn2, Cyfip2, Aen, Prune2, Spp1, Gadd45b, and Sphk1 were significantly reduced along with considerable increases of the levels of Gas1, Angptl4, Fn1, Tpx2, Egfr, Snai2, Sfrp2, Gas1, and Lpar1 genes after KRG treatment. Above indicated interesting outputs elucidated that the genes in charge for apoptosis and inflammation processes were down-regulated at significant manner by KRG treatment. From these observations we can concluded that the KRG treatment potentially defending diabetes correlated cardiac problems at the level of its genome.

A K Güliz has completed her Msc studies from Ege University Faculty of Science Biochemistry Department and initiated her PhD studies in 2010 in the same department. She has been working as a research assistant in Ege University Faculty of Science Biochemistry Department since 2010 and also as a researcher in Ege University Pharmacokinetic Drug Development & Research Center (ARGEFAR) Biosimilar Products Department Proteomics Unit since 2013. She is a funded researcher in two projects about nanoparticular anticancer agent researches.

Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. Ovarian cancer cells can develop folate receptors that are not overexpressed on somatic cells, making it possible to exploit these receptors for anticancer therapy. In addition magnetic agents can be directed to tumor tissues via an external magnetic field and this may mostly eliminate the side effects of classical oral treatment. Doxorubicin is used for ovarian cancer therapy but its usage is limited due to the side effects. Recent advances in molecular and cellular biology have inspired scientists and nanotechnologists to model nanocarriers after red blood cells, which are nature’s long circulating delivery vehicles. Properties of red blood cells such as their structure and surface proteins have been taken as design cues to devise the next-generation delivery platforms. In this work we aimed to design a novel biomimetic doxorubicin nanocarrier system that targeted with magnetically and biomolecularly via folate ligand for ovarian cancer therapy. Magnetic nanoparticles were prepared with the combination of magnetite, polysaccharide and polyethylene glycol. Doxorubicin was loaded to this carrier system. Finally, red blood cells and folate ligand were used to acquire biomimetic properties and biomolecularly targeting, respectively. This biomimetic doxorubicin nanocarrier could have potential for effective ovarian cancer treatment.

Acknowledgement:
We would like to thank for financial support received from the Research Foundation of Ege University (Project ID: 12 FEN 028).

Dae-Duk Kim has completed his PhD in 1995 from Rutgers-The State University of New Jersey in the USA and worked as a Post-doctoral fellow at the University of Washington in Seattle. He was a faculty member of the College of Pharmacy at Pusan National University until he transferred to his current position at Seoul National University in 2003. He has published more than 150 papers in peer-reviewed international journals, and has served as the Editor-in-Chief of the Journal of the Pharmaceutical Investigation.

Deoxycholic acid (DOCA) and 3-aminomethylphenylboronic acid (AMPB)-conjugated self-assembled nanoparticles (NPs) of chondroitin sulfate A (CSA) were prepared for tumor targeting and penetration. The hydrophobic DOCA derivative was conjugated to the hydrophilic chondroitin sulfate A (CSA) backbone, followed by conjugation of AMPB to CSA-DOCA. Loading doxorubicin (DOX) to these CSA-DOCA and CSA-DOCA-AMPB NPs resulted in NPs of around 230 nm mean diameter, narrow size distribution, negative zeta potential, and relatively high drug encapsulation efficiency (up to 85%). CSA-DOCA and CSA-DOCA-AMPB NPs exhibit improved in vitro cellular uptake and penetration as evidenced by confocal laser scanning microscopy and flow cytometry. In vivo tumor targeting and penetrating by these NPs, based on both CSA-CD44 receptor and boronic acid-sialic acid interactions, was revealed using near-infrared fluorescence (NIRF) imaging in the tumor-xeno grafted mouse mode. Both passive and active strategies seem to have contributed to the in vivo tumor target ability of the NPs. These NPs could be a promising theranostic nanoplatform for cancer therapy and imaging.

Eun-Hwa Sohn has completed his PhD from Sungkyungkwan University. She has researched pharmacological effects of natural substances and their mechanisms on inflammation. She works at the department of herbal medicine resource as a chair in Kangwon National University. She is on the Editorial Board of Korean Journal of Plant Resources. She has over 100 publications including a book, book chapters and peer reviewed articles.

An allergy is a hypersensitivity disorder of the immune system. Arctium lappa L., known as a burdock, is a popular edible vegetable but its anti-allergic potential remains unknown. In this study, the anti-allergic effect of A. lappa extracts was determined using Sprague-Dawley rats, ICR mice, and RBL-2H3 mast-like cells. Among fractions extracted with several solvents, EtOH fraction of A. lappa (ALE) at 100 μg/ml showed the maximal inhibitory effect on β-hexosaminidase release and the high cell viability in RBL-2H3 cells. Administration of ALE (100 mg/kg) highly suppressed the passive cutaneous anaphylaxis (PCA) induced by anti-DNP-specific IgE insult in rats, and attenuated the compound 48/80-induced systemic allergic reaction, anaphylaxis, and histamine release in mice. In order to identify the active compound from ALE with anti-allergic action, we subsequently performed further fractionation with determining β-hexosaminidase assay in every sub-fractions and its main active component was identified as an oleamide. Oleamide attenuated the secretion of histamine and β-hexosaminidase, and the production of allergic-related cytokines such as IL-4 and TNF-α in RBL-2H3 cells treated with compound 48/80 or A23187/PMA. In addition, oleamide administration suppressed FcεRI-tyrosine kinase Lyn-mediated pathway. The anti-allergic effect of ALE and its bioactive component oleamide may have beneficial effects in the treatment of human allergic diseases

Hyeon-Joong Kim has completed his bachelor's degree from Konkuk University and got a veterinary medical license at the age of 24 years. He studies at Konkuk University College of Veterinary Medicine as a PhD candidate from 2011. He is the writer of science webzine, Science-on, and he has published 6 papers in reputed journals.

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer’s disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using AD animal models. Gintonin induced [Ca2+]i transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated [Ca2+]i transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin (25, 50, or 100 mg/kg/day, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 2 weeks) also significantly attenuated amyloid-β protein (Aβ)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments, such as decreased acetylcholine concentration, decreased ChAT activity and immunoreactivity, and increased AChE activity. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to Aβ and could be utilized for AD prevention or therapy.

Raoufa A I Abdel Rahman has completed her PhD in 2003 at Alexandria University, Faculty of Agriculture, Genetics Dep., throught a collaborative scholarship with University of Georgia, Athens, USA. She completed a research project entitled "Exploring IRES mediated discistrons for the phytoremediation of Mercury". Currently, she is the director of Pharmaceutical Bio-products Research Dep., City of Scientific Research and Technology Applications, Alex., Egypt. Her main research interests are using plant tissue culture and genetic engineering techniques to conserve rare and endangered plant species, as well as enhancement the productivity of important pharmaceutical compounds from plants. She is working in several projects dealing with the production of antiviral, anticancer, and antioxidant compounds from plants using in-vitro cultures.

Over the past three decades, plant cell and tissue culture and plant biotechnology techniques have proved to be a valuable tool for study biosynthesis and production of plant secondary products. Rosmarinic acid (RA) is a natural phenolic compound produced by variety species of Lamiaceae and Boraginaceae families. In the recent few years, RA has attracted attention due to its antiviral, antibacterial, anti-inflammatory and anti-allergic activities. In the present study, the efficiency of using plant tissue culture techniques as a promising alternative method for the production of RA from basil and lemon balm was tested. Callus and shoot cultures were established using different types of explants and medium composition to test the optimum condition for their production. Results showed that leaf explants were the best explants for callus production. MS medium containing 1mg/l BA and 1mg/NAA (MS2) was the best medium for callus growth in lemon balm while MS4 was the optimum media for basil. Stem segments and shoot tips were used as explants for production of shoot cultures in lemon balm and basil. RA levels were determined in control, callus and shoot cultures. Results showed that callus and shoot cultures accumulated higher levels of RA compared to control. RA levels ranged from 9.42±1.27 to 38.25±0.73 ug/mg plant dry weight. Shoots produced 3 and 2.7 folds higher rosmarinic acid levels compared to control in lemon balm and basil. The overall results indicated that plant tissue culture is an efficient tool for RA production from basil and lemon balm plants.

Jungsook Cho has completed her PhD from State University of New York at Buffalo, USA and has been engaged as a Professor at Dongguk University, S Korea, since 1996. She is the director of Drug Target Control Research Center.

CCL2, a member of the CC-chemokine subfamily, plays an important role in recruiting leukocytes to inflammatory sites. Studies have suggested that CCL2 and its major receptor CCR2 are associated with a variety of neurological disorders. However, emerging evidence indicates that CCL2 exerts neuro modulatory actions and plays a neuroprotective role in certain injuries and insults, although the underlying mechanism remains elusive. The present study investigated the neuroprotective effects of CCL2 against excitotoxic insult and elucidated the intracellular signaling cascades triggered by this chemokine using primary cultured rat cortical neuronal cells as a model. CCL2 alone had no effect on viability and caspase 3 activity of the cultured cells under the prevailed experimental conditions. Rather, it significantly attenuated excitotoxic neuronal damage as well as reactive oxygen species production induced by N-methyl-D-aspartate (NMDA)-or L-glutamate, and inhibited the NMDA-induced activation of caspase 3. CCL2 induced phosphorylation of MEK1/2, extracellular regulated kinase (ERK)1/2, p90RSK, and Aktin concentration- and time-dependent manners. CCL2-induced activations of ERK1/2 and p90RSK were inhibited by U0126, a MEK1/2 inhibitor, suggesting that CCL2-triggered activation of p90RSK is mediated through the MEK/ERK signaling pathway. CCL2-induced phosphorylations of Akt, ERK1/2, and p90RSK were inhibited by the broad spectrum PI3K inhibitors wortmannin and LY294002, as well as the PI3Kγ inhibitor AS605240, suggesting that these three kinases are downstream modulators of PI3Kγ in the CCL2 signaling pathway. Taken together, these findings contribute to the understanding of the neuroprotective role of CCL2 and its signaling pathways in the brain where PI3Kγ plays a vital role.

Kim Jinwoong has completed his PhD under the guidance of A Douglas Kinghorn from University of Illinois at Chicago, USA. He served as the Director of BK21 Applied Pharmaceutical Life Sciences Research Division (2006-2013), Associate Dean (2005-2007), College of Pharmacy in Seoul National University. He also worked as president in Korean Society of Pharmacognosy. He has published more than 120 SCI (E) papers in reputed journals and has been served as the Editorial Advisory Board Member in Planta Medica, J. Ethnopharmacology, Drugs of the Future, and Anti-Cancer Agents in Medicinal Chemistry.

Swine based agro-industries throughout the world are in big threat of new PEDV infection due to lack of efficient prophylactic defenses as well as dependable curing agents. Bioactivity-guided fractionation of a methanol soluble extract from radix of Saposhnikovia divaricata led to the isolation of three new (13) together with ten known coumarins (413). The structures of new isolates (13) were established by extensive spectroscopic analysis and their absolute configurations were assigned based on ECD spectra calculation and analysis. Among all isolates, hyuganin C (5), revealed strongest inhibitory effect on PEDV replication. Quantitative real-time PCR data showed inhibitory effect of 5 on genes responsible for synthesis of PEDV vital structural proteins (GP6 nucleocapsid, GP2 spike, and GP5 membrane) in a dose-dependent manner. Also, compound 5 demonstrated the inhibitory effect on PEDV GP6 nucleocapsid and GP2 spike protein synthesis as analyzed by western blotting. This study represents a new class of chemical entities for developing anti-PEDV agents.

Hyun Jung Koo has completed her PhD from Sungkyunkwan University, School of Pharmacy and Postdoctoral studies from Gachon University, Republic of Korea. She is the Assistant Professor of Korea National College of Agriculture and Fisheries, Department of Medicinal and Industrial Crops. Her research interests have focused on discovery and identification of novel drug sources from medicinal plants and investigate molecular mechanisms of diseases. She published more than 20 papers in reputed journals.

Nonalcoholic fatty liver disease (NAFLD) has been recognized as the most common hepatic inflammatory disorders caused by an accumulation of fat deposits in the liver. COX-2 expression is related to the inflammatory phenomena in the early phases of chronic liver diseases and to the induction of hepatocarcinogenesis. The present study investigated the anti-inflammatory effects of a root extract of Cynanchum wilfordii in order to elucidate the molecular mechanisms of action of the protective properties on NAFLD. Mice were randomly divided into 6 groups with 6 mice in each group: (1) normal control chow diet plus vehicle (NC) (2) high-cholesterol diet with 10% fructose in the drinking water (HCD+FRU) (3) HCD+FRU plus 50 mg/kg b.w./day (4) HCD+FRU plus 100 mg/kg b.w./day of CWE (5) HCD+FRU plus 200 mg/kg b.w./day of CWE or (6) HCD+FRU plus 10 mg/kg b.w./day of simvastatin via oral gavage for 12 weeks. Our results indicate that the severity of histological changes and lipid accumulation in the liver were decreased by CWE treatment. Moreover, GOT, GPT, and cholesterol levels showed significantly and dose-dependently reduced in the CWE treatment groups (50, 100, and 200 mg/kg) compared with HCD. We observed a significant high expression of COX-2 in the liver of HCD group and administration of CWE significantly reduced the expression of COX-2. These results suggested that the root of C. wilfordii may be used for the prevention and treatment of nonalcoholic fatty liver disease.

Aravinthan Adithan has completed his MS from Bharathidasan University, India. He is a student for PhD course in Chonbuk National Univeristy, Republic of Korea. He has published more than 5 papers in reputed journals.

Present study aimed to discover the protective role of ginsenoside Rb1 against homosysteine (Hcy) induced apoptosis in rats bone marrow derived endothelial progenitor cells (EPCs). A Panax ginseng contains huge numbers of ginsenosides crucial constituents for its pharmacological potential. In the market, presently existing cardioprotective drugs exhibits considerable noxious effect after the treatments. People everywhere in the globe looking for natural products mediated remedies against cardiac diseases. To fulfill this investigation, in the presence or absence of ginsenoside Rb1 along with Hcy at a concentration of 200 µM, EPCs were incubated for the time duration of 24 h. Immunoblotting assays were conducted in order to identify the antiapoptotic activities of ginsenoside Rb1 against Hcy treated EPCs. Bax and caspase-3 as a proapoptotic markers and Bcl-2 as an antiapoptotic marker were analyzed by immunoblotting. FACS examination also articulates that the substantial rises of apoptosis initiation over induction of Hcy. On the other hand, pretreatment of ginsenoside Rb1 displays extensive increases of Bcl-2 along with reductions of Bax and caspase-3 markers. Ginsenoside Rb1 pretreatment also rises of survival rate of EPCs at significant manner. All the above observations indicated that the Hcy induced apoptosis in EPCs were potentially declined by the treatment of ginsenoside Rb1.

Boo-Yong Lee has completed his PhD from Korea University and Postdoctoral studies from University of Georgia, School of Food Science. He is the Professor of Dept. of Food Science and Biotechnology, CHA University. He has published more than 130 papers in reputed journals and has been serving as an Editorial Board Member of The Korean Society of Ginseng, Korean Society of Food Science and Technology, and The Korean Society of Food Science and Nutrition.

Ecklonia cava, a kind of brown alga native to Korea and Japan seas, includes biologically active polyphenols. The effect of SeapolynolTM (SN) extracts in Ecklonia cava and dieckol (DK), a major component of SN has shown anti-diabetic effects on C57BL/KsJ-db/db mice. 5 weeks old male db/db mice were divided into six groups, control (db/db), Rosi (db/db+rosiglitazone 10mg/kgBW/day), SNLD (db/db+SN 60mg/kgBW/day), SNHD (db/db + SN 150mg/kgBW/day), DKLD (db/db + DK 30mg/kgBW/day), DKHD (db/db + DK 120mg/kgBW/day) administered mice. SN and DK supplementation groups significantly reduced final body weight, water intake, fasting blood glucose, plasma insulin, and c-peptide levels but to the contrary increased plasma adiponectin levels. Plasma lipid profiles including triacylglycerol, total cholesterol, HDL and LDL-cholesterol reduced SN and DK treatment groups. Moreover, administration of SN and DK activated insulin receptor substrate-1 (IRS-1) signaling pathway and glucose transporter type 4 (GLUT4) associated with insulin sensitivity and blood glucose regulation in visceral fat of diabetic mice. This study suggests that SN and DK administration might have potential anti-diabetic effects by regulation of IRS-1 signaling pathways in type 2 diabetes.