Volume: 16  Issue: 3 - 2019
Hide Abstracts | << Back
1.Evaluation of Alchemilla persica Rothm. antidiabetic activity on mice induced by alloxan
Serkan Özbilgin, Hanefi Özbek, Neriman İpek Kırmızı, Burçin Ergene Öz, Ekin Kurtul, Bade Cevriye Özrenk, Gülçin Saltan İşcan, Özlem Bahadır Acıkara
Page 0
GİRİŞ ve AMAÇ: Alchemilla türleri Türk halk tıbbında diyabetin yanında birçok hastalığın da tedavisinde kullanılmaktadır. Bu cinse ait olan Alchemilla persica; Doğu Anadolu, Kafkasya, Kuzey ve Kuzeydoğu İran ile Kuzey Irak’ta yetişmektedir.
YÖNTEM ve GEREÇLER: Bu çalışmada Alchemilla persica’nın halk arasındaki kullanımını doğrulamak amacıyla; toprak üstü kısım ve köklerinin sulu-metanollü ekstrelerinin alloksan indüklü diyabetik fareler üzerindeki hipoglisemik etkileri test edilmiştir.
BULGULAR: Test edilen ekstrelerden hiçbiri kan glukoz düzeyini kayda değer biçimde düşürmezken, A. persica toprak üstü kısımları kan glukoz düzeyini 100mg/kg ve 200mg/kg dozlarda önemli ölçüde artırmıştır.
TARTIŞMA ve SONUÇ: Bu çalışma A.persica’nın antidiyabetik olarak kullanımını doğrulamamıştır.
INTRODUCTION: Alchemilla species are used in Turkish folk medicine for treatment of many disease together with diabetes. Alchemilla persica belonging to this genus, widely distributed in East part of Anatolia as well as Caucasica, north and northeast of Iran and north Iraq.
METHODS: In present study Alchemilla persica aerial part and root methanolic-water extracts were evaluated for their hypoglycemic activities on alloxan induced diabetic mice in order to verify its usage in folk medicine.
RESULTS: Any of the tested extracts did not exhibit significant lowering effect on blood glucose levels. On the other hand A. persica aerial parts increased blood glucose level at the döşe of 100 mg/kg and 200 mg/kg notably.
DISCUSSION AND CONCLUSION: A. persica usage for its antidiabetic activity is not confirmed in present study.
Abstract | Full Text PDF

RESEARCH ARTICLE
2.Synthesis and swelling behavior of sodium alginate / poly (vinyl alcohol) hydrogels
Demappa Thippaiah, Shivakumara Lachakkal Rudrappa
Pages 252 - 260
INTRODUCTION: Hydrogels are macromolecular networks able to absorb and release water/biological fluids in a reverse phase manner, in response to specific environmental stimuli. Such stimuli –sensitive behavior makes hydrogels interesting for the design of smart devices applicable to a variety of technological fields. They are able to absorb and retain 10-20% and upto 1000 times of water or biological fluids than their dry weight.
METHODS: The authors are synthesized sodium alginate/poly (vinyl alcohol) hydrogels. These hydrogels are characterized by FTIR, SEM, swelling properties of hydrogels in different pH, in salts, different temperature, different acids and bases.

RESULTS: The authors studied and reported that the swelling effects or variations such as effect of salts, acids, bases, temperature and pH. The effect of cross-linking agent glutaraldehyde shows that the 8 mL glutaraldehyde has the highest swelling rate as compare to that of 10 mL and 12 mL.
DISCUSSION AND CONCLUSION: In this work authors studied the swelling degree in different acids and bases. We are concluded that the degree of swelling is decreased with increase in the concentration of the glutaraldehyde and also depending on the concentration of the acids. The swelling degree of PVA/SA hydrogels are gradually increased with increase in concentration of acids (low p H). The swelling of hydrogels decreases with increase of pH ( > 7) or at high alkaline. In the effect of salt solutions the swelling behavior is found to be in the order: K+ > Na + > Ca2+ > Mg2+.
Abstract | Full Text PDF

3.Palmitic Acid-Pluronic F127-Palmitic Acid Penta-Block Copolymer as a Novel Nanocarrier for Oral Delivery of Glipizide
Vipan Kumar Kamboj, Prabhakar Kumar Verma
Pages 265 - 272
INTRODUCTION: The aim of the present study is to develop nanotechnology-based oral formulations of Glipizide to enhance bioavailability and to eliminate the frequent oral administration of the conventional dosage form. Glipizide is an antidiabetic drug with short biological half-life with limited oral bioavailability. Noval Palmitic acid-Pluronic F127-Palmitic acid (PAF127) pentablock copolymer based prolonged release glipizide nanoparticles (GN) were prepared and screened for in vitro and in vivo studies.
METHODS: GN was prepared using novel PA-F127 pentablock copolymer by solvent evaporation technique. The prepared nanoparticles were evaluated for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, percentage yield, drug excipient compatibility using FTIR and DSC analysis, XRD, SEM, In vitro drug release studies, stability studies and in vivo pharmacokinetic studies.
RESULTS: The results of FTIR and DSC analysis revealed the absence of drug-excipient interactions. The optimized GN1 has particle size 242.60 ± 4.20 nm, PDI 0.171 ± 0.014 and zeta potential -21.41 ± 0.462 mV. Prepared nanoparticles were spherical in shape and showed semi-amorphous characteristics. In vitro release studies showed 34.43 ± 4.8 % drug was released in first 8 h, 56.11 ± 4.12 % glipizide were released further for 24 h. The GN1 was found to be stable at 5 ± 3 ºC up to three months. Pharmacokinetic studies showed that the orally administered GN1 were superior with Cmax 2.35 fold, tmax 1.6 fold, area under the curve (AUC0→∞) 3.3 fold and mean residence time (MRT) 1.2 fold as compared to pure glipizide (p < 0.05).
DISCUSSION AND CONCLUSION: The study concluded that the bioavailability of newly developed GN1 was successfully prolonged and frequent oral administration problem with conventional dosage form can be defeated for diabetes treatment.
Abstract | Full Text PDF

4.Anti-cancer and anti-inflamatory effects of Centaurea solstitialis extract on human cancer cell lines
Mehlika Alper, Hatice Güneş
Pages 273 - 281
GİRİŞ ve AMAÇ: Bitkilerden elde edilen doğal ürünler, kanser dahil çeşitli hastalıkların tedavisinde uzun yıllardır kullanılmaktadır. Centaurea solstitialis subsp. solstitialis’in Türk geleneksel tıppında yeri olduğu bilinmektedir. Bu araştırma, Muğla ilinden toplanan C. solstitialis’in çiçekli kısımlarından elde edilen etanolik özütün in vitro biyolojik etkilerini belirleyen ilk çalışmadır.
YÖNTEM ve GEREÇLER: Özütün Daudi, A549 ve HeLa kanser hücrelerine ve normal BEAS-2B hücre hattına karşı sitotoksik aktivitesi MTT testi ile belirlendi. Apoptotik hücre ölümü akış sitometri analizi ve kaspaz-3 aktivite deneyleriyle araştırıldı. Özüt ile muamele edilen hücreler tarafından üretilen anjiyojenik faktör VEGF salınımı ve sitokinlerden IL-lα, IL-6 ve TNF-α'nın salınımı ELISA testleriyle ölçüldü.
BULGULAR: Bitki özütü kullanılan tüm kanser hücre hatlarına karşı sitotoksik etki gösterirken, özüte karşı en duyarlı hücrelerin 63.18 μg/ml and 69.27 μg/ml olan IC50 değerleri ile sırasıyla HeLa ve Daudi hücreleri olduğu gözlendi. Seçici sitotoksisite HeLa ve normal BEAS-2B hücre hatları arasında tespit edildi. Bitki özütü S ve G2 fazlarında hücre döngüsü arrestine yol açtı. Buna ilave olarak, HeLa ve A549 hücrelerinde apoptotik hücre ölümü kaydedildi. Ayrıca bitki özütü A549 hücrelerinin VEGF salgılamasında anlamlı bir düşüşe yol açarken, A549 ile Daudi hücrelerinin IL-lα, IL-6 ve TNF-α salgılamasında önemli değişime neden oldu.
TARTIŞMA ve SONUÇ: Bu bulgular kanser tedavisi ve sitokin salgısının modülasyonunda gerekli olan doğal ilaçların geliştirilmesi için C. solstitialis'in çiçekli kısımlarının potansiyel bir kaynak olabileceğini göstermektedir.
INTRODUCTION: Natural products originating from plants have been used for many years in the treatment of various diseases including cancer. Centaurea solstitialis subsp. solstitialis is used in Turkish folk medicine. This study was the first to determine in vitro biological effects of ethanolic extract from flowering parts of C. solstitialis L. ssp. solstitialis collected from Mugla province.
METHODS: Cytotoxic effect was evaluated against Daudi, A549 and HeLa cancer cells and one normal BEAS-2B cell line using MTT assay. Flow cytometric analysis and caspase-3 activity assay were performed to detect apoptotic cell death. Angiogenic factor (VEGF) secretion and the release of IL-1α, IL-6 and TNF-α by the cells treated with the extract were measured using ELISA assay.
RESULTS: The extract exhibited cytotoxic activities against the all cancer cell lines used but HeLa and Daudi were the most sensitive cells with IC50 values of 63.18 μg/ml and 69.27 μg/ml, respectively. Selective cytotoxicity was observed between HeLa and normal BEAS-2B cell lines. The extract arrested the cell cycle at the S and G2 phases. In addition, apoptotic cell death was detected in HeLa and A549 cells. Moreover, the plant extract caused a significant decrease in VEGF secretion of A549 cells and a fluctuation in IL-1α, IL-6 and TNF-α secretion of A549 and Daudi cells.
DISCUSSION AND CONCLUSION: These observations suggest that flowering part of C. solstitialis may be a potential source in the development of natural drugs for the treatment of cancer and modulation of cytokine secretion.
Abstract

5.An in vitro study on the cytotoxicity and genotoxicity of silver sulphide quantum dots coated with meso-2,3-dimercaptosuccinic acid
Deniz Ozkan Vardar, Sevtap Aydin, İbrahim Hocaoglu, Havva Yagci Acar, Nursen Basaran
Pages 282 - 291
GİRİŞ ve AMAÇ: Gümüş sülfür (Ag2S) kuantum noktaları (QDs), hem görüntüleme hem de ilaç/gen hedefleme için büyük aktiviteleri nedeniyle biyo-görüntüleme sisteminde oldukça gelecek vaad eden nanomalzemelerdir. Mezo-2,3-dimerkaptosüksinik asit (DMSA) ile kaplanmış Ag2S QD'lerin toksisitesi hakkında yeterli çalışma yoktur. Bu çalışmada Çin hamster akciğer fibroblast (V79) hücrelerinde DMSA ile kaplanmış Ag2S QD'lerin geniş bir konsantrasyon aralığında (5-2000 µg/mL) sitotoksisitesini belirlemeyi amaçladık.²
YÖNTEM ve GEREÇLER: Hücre canlılığı 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolium bromid (MTT) ve nötral kırmızı alım (NRU) deneyleri ile belirlendi. DMSA / Ag2S QD'lerin genotoksik ve apoptotik etkileri sırasıyla comet analizi ve gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) tekniği ile değerlendirildi.
BULGULAR: Ag2S QD'lerin en yüksek dozlarında (2000 μg/mL) hücre canlılığı MTT ve NRU deneylerinde sırasıyla 54.0±4.8% ve 65.7±4.1% olarak bulundu. Ancak hücre canlılığı 400 μg/mL (MTT deneyi) ve 800 μg/mL (NRU deney) üzerinde azalmıştır. İncelenen konsantrasyonlarda DNA hasarının DMSA/Ag2S QD'ler tarafından indüklenmediği belirlenmiştir. P53, kaspaz-3, kaspaz-9, bax, Bcl-2 ve survivin genlerinin mRNA eksprsyon düzeyleri 500 ve 1000 ug /mL DMSA / Ag2S QD'lere maruz kalan hücrelerde değişmiştir.
TARTIŞMA ve SONUÇ: DMSA / Ag2S QD'lerin yüksek dozlarda sitotoksik etkilerinin apoptotik yollarla ortaya çıkabileceği görülmektedir. Bununla birlikte, DMSA / Ag2S QD'ler, düşük dozlarda biyolojik olarak uyumlu görünmektedir, bu da onları hücre görüntüleme uygulamaları için uygun kılmaktadır.
INTRODUCTION: Silver sulfide (Ag2S) quantum dots (QDs) are highly promising nanomaterials in bioimaging system due to their great activities on for both imaging and drug/gene delivery. There are no enough study on the toxicity of Ag2S QDs coated with meso-2,3-dimercaptosuccinic acid (DMSA). In this study, we aimed to determine the cytotoxicity of Ag2S QDs coated with DMSA in Chinese hamster lung fibroblast (V79) cells over a wide range of concentrations (5-2000 µg/mL).
METHODS: The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays. The genotoxic and apoptotic effects of DMSA/Ag2S QDs (5-2000 μg/mL) were also assessed by comet assay and real time polymerase chain reaction (RT-PCR) technique, respectively
RESULTS: The cell viability were found to be 54.0±4.8% and 65.7±4.1% at the highest dose (2000 µg/mL) of Ag2S QDs using MTT and NRU assays, respectively. Although the cell viability decreased above 400 μg/mL (MTT assay) and 800 μg/mL (NRU assay), it was observed that DNA damage was not induced by DMSA/Ag2S QDs at the studied concentrations. The mRNA expression levels of p53, caspase-3, caspase-9, bax, Bcl-2, and survivin genes were altered in the cells exposed to 500 and 1000 µg/mL of DMSA/Ag2S QDs.
DISCUSSION AND CONCLUSION: It appears that the cytotoxic effects of DMSA/Ag2S QDs may occur at the high doses through the apoptotic pathways. However DMSA/Ag2S QDs appear to be biocompatible at low doses, which make them well-suited for cell labeling applications.
Abstract | Full Text PDF

6.Phytochemical screening, metallic ion content and from its impact on Anti psoriasis activity of Calendula officinalis and Phlebodium decumanum aqueous leaf extracts in animal experiment model
Kuntal Das, Someswar Deb, Tejaswini Karanth
Pages 292 - 302
INTRODUCTION: The aim of this study is to evaluate the influence of metal ions present in soil as well as in the leaves samples of Calendula officinalis and Phlebodium decumanum for the treatment of psoriasis.
METHODS: Looking at the objective, soils and leaves samples were estimated for metal ions by atomic absorption spectrophotometer to determine the influence in anti-psoriatic activity. Thereafter Imiquimod-induced dermatitis lesions were created in grouped mouse. Two plant extracts (aqueous) separately as well as in combinations and standard Retino-A (0.05%) were used. Psoriasis severity index (PSI) was evaluated by phenotypic (redness, erythema, and scales) and histological features (epidermal thickness). Further content of phytochemicals in terms of extract was correlated with the effect of psoriasis activity.
RESULTS: We observed redness, erythema and scales and the histological features and found a progressive reduction (P < 0.05) in the severity of psoriatic lesions (redness, erythema, and scales) from day 7 to 21st day and decreased epidermal thickness in animals treated with combined extracts at the dose of 200 mg/kg b.w. Furthermore plant samples procured from Nandi Hill’s, Bangalore, showed better uptake of metals with respect to Fe (2.05 mg/kg), Cu (0.78 mg/kg) and Zn (1.12 mg/kg) which showed positive impact on procurement of maximum amount of extracts that further correlated with the activity, indicated significant reduction of psoriatic lesions.
DISCUSSION AND CONCLUSION: Results revealed that significant dose dependent antipsoriasis activity of combined aqueous extracts of Calendula officinalis and Phlebodium decumanum as well as metal ions are also had impact on the procurement of extracts and said activity.
Abstract | Full Text PDF

7.Anti-Angiogenic activity of flunarizine by in ovo, in vitro and in vivo assays.
Chandana Kamili, Ravi Shankar Kakaraparthy, Uma Maheshwararao Vattikuti
Pages 303 - 309
INTRODUCTION: The involvement of T-type calcium channels in cell proliferation and the role of sodium channels in cell migration have been extensively studied in angiogenesis. In the present study Flunarizine, a dual sodium /calcium channel blocker; was selected to evaluate its anti-angiogenic potential. This can be therapeutically beneficial in the diseases caused due to pathologically excess angiogenesis.
METHODS: The anti-angiogenic activity of ion channel blocker was screened by chick chorioallantoic membrane assay (in ovo), Rat aortic ring assay, Endothelial Cell Proliferation Assay, Transwell Migration Assay, Matrigel Cord-Like Morphogenesis Assay (in vitro) and sponge impantation method (in vivo). The anti-angiogenic activity of the test drug was compared with the standard anti-angiogenic drug Bevacizumab and in addition, the test responses were compared with the angiogenic factor VEGF, at a maximal concentration of 500pM.
RESULTS: In the chorioallantoic membrane assay, number of branching points and angiogenic score were evaluated and significant results were observed at 10-5M and 10-4M. In the aortic ring assay reduction in the area of sprouts were observed with 5-10µM and a significant reduction in weight of sponges, number of blood vessels formed and hemoglobin content were observed at all the three tested concentrations of Flunarizine in the sponge implantation method. In the studies on Human umbilical vein endothelial cells the test drug (1-100 nM) showed significant inhibition of proliferation, migration and decrease in network length of cord like tubes in a dose dependent manner.
DISCUSSION AND CONCLUSION: Flunarizine has significant anti-angiogenic action by inhibiting the cell proliferation, migration and cord like tube formation, which have resulted by blocking the T-type calcium and sodium channels.
Abstract | Full Text PDF

8.Superior solubility and dissolution of zaltoprofen via pharmaceutical cocrystal
Prabhakar Panzade, Giridhar Shendarkar
Pages 310 - 316
GİRİŞ ve AMAÇ:
Amaç: Farmasötik kok kristal, zayıf çözünür ilaçların çözünürlüğünü ve çözünmesini arttırmak için umut veren bir araçtır. Zaltoprofen yaygın çözünürlüğe sahip nonsteroid antiinflamatuar ilaçtır. Bu çalışma, çeşitli koformerlerin taranması yoluyla farmasötik kokteyli aracılığıyla zaltoprofenin çözünürlüğünü ve çözünmesini arttırmak için üstlenilmiştir.
YÖNTEM ve GEREÇLER: Gereç ve Yöntem: Kuru öğütme yöntemi ile 1: 1 ve 1: 2 oranında ilaç: koformer oranında zaltoprofen kristalleri hazırlandı. Erime noktası ve kristalin fazın çözünürlüğü belirlendi. Potansiyel kristaller diferansiyel tarama kalorimetrisi (DSC), kızılötesi spektroskopi (IR) ve toz X ışını kırınımı (PXRD) ile karakterize edildi. Coriztaller çözünme hızına ve stabilite çalışmasına tabi tutuldu.
BULGULAR: Sonuçlar: Zaltoprofen-nikotinamid (ZFN-NIC) Cocrystals erime noktasında ve çözünürlükte sapma göstermiştir. Kristaller, nikotinamid ile hem 1: 1 hem de 1: 2 oranında elde edildi. Kızılötesi analizi, zaltoprofenin karakteristik bantlarının kaymasını belirgin bir şekilde gösterdi. Kristallerin kristallenmesi XRPD paterninden belirgin olarak görülmüştür ve 2θ değerindeki yoğun zirvelerdeki kayda değer farklılıklar gözlenmiştir. Kristallerin DSC spektrumları, erime noktasına benzer değiştirilmiş endotermler sergiledi. Kristaller, daha hızlı çözünme oranı ve saf ilaçla karşılaştırıldığında çözünme derecesinde% 55 artış gösterdi. Kristaller, oda sıcaklığında ve hızlandırılmış koşullarda kararlı bulundu.
TARTIŞMA ve SONUÇ: Sonuç: Hazırlanan kristaller, saf ilaca kıyasla daha fazla çözünürlük ve çözünme sergilemiş ve oda sıcaklığında ve hızlandırılmış koşullarda sabit bulunmuştur.
INTRODUCTION: Objective: Pharmaceutical cocrystal is a promising tool to enhance solubility and dissolution of poorly soluble drugs. Zaltoprofen is nonsteroidal anti-inflammatory drug with prevalent solubility problem. The present study was undertaken to enhance the solubility and dissolution of zaltoprofen through pharmaceutical cocrystal by screening various coformers.
METHODS: Materials and Methods: Cocrystals of zaltoprofen were prepared in 1: 1 and 1: 2 ratio of drug: coformer by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystals were characterized by differential scanning calorimetry (DSC), infrared spectroscopy (IR) and powder X-ray diffraction (PXRD). Corystals were subjected to dissolution rate and stability study.
RESULTS: Results: Zaltoprofen-nicotinamide (ZFN-NIC) Cocrystals demonstrated deviation in melting point and solubility. The cocrystals were obtained in both 1: 1 and 1: 2 ratio with nicotinamide. The analysis of Infrared noticeably indicated the shifting of characteristic bands of zaltoprofen. Crystallinity of cocrystals was evident from the XRPD pattern and notable difference in 2θ value of intense peaks. DSC spectra of cocrystals exhibited altered endotherms analogous to melting point. Cocrystals showed faster dissolution rate and 55% increase in the extent of dissolution compared to pure drug. The cocrystals were found stable at room temperature and accelerated conditions.
DISCUSSION AND CONCLUSION: The prepared cocrystals exhibited greater solubility and dissolution as compared to pure drug and found stable at room temperature and accelerated conditions.
Abstract

9.Effect of Aerial Parts and Root Extracts from Four Ferulago Species on Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats
Songül Karakaya, Didem Yılmaz Oral, Serap Gur, Hayri Duman, Ceyda Sibel Kılıc
Pages 317 - 325
GİRİŞ ve AMAÇ: Ferulago türleri Türkiye'de afrodizyak olarak kullanılmaktadır, bu nedenle in vivo ve in vitro olarak dört Ferulago türüne ait ekstrelerin korpus kavernosum (CC) üzerindeki gevşetici etkisini göstermeyi amaçladık.
YÖNTEM ve GEREÇLER: 30 yetişkin erkek Sprague-Dawley sıçanlar kontrol ve diyabetik olarak iki gruba ayrıldı ve diyabet grup 40 mg/kg streptozotosin’in intraperitonal tek seferlik enjeksiyonu ile indüklendi. Kavernosal sinirlerin uyarılmasıyla in vivo erektil yanıtlar elde edildi ve sıçanlarda intrakavernozal ekstraktların enjeksiyonu sonrasında tekrarlandı ve veriler intrakavernozal basınç (ICP)/ortalama arteriyel basınç (MAP) ve toplam ICP olarak ifade edildi. CC striplerin gevşetici ve kasılma yanıtları, ekstrelerin varlığında veya yokluğunda analiz edildi.
BULGULAR: Ekstreler hem kontrol hem de diyabetik sıçanlar üzerinde aktif olduğu bulundu. Ekstreler ile alınan (özellikle Ferulago bracteata kök metanol ekstresi) maksimum gevşeme yanıtları (% 98.30 ± 2.6) L-NAME (44.8 ± 1.8) ile inkübasyondan sonra azalmıştır. ODQ, çözünebilir guanilat siklaz inhibitörü, kontrol sıçanlarından CC'de ekstrelerin indüklediği maksimum gevşemenin% 77'sini inhibe ettiği görülmüştür.

TARTIŞMA ve SONUÇ: Sonuç olarak bu türler erektil disfonksiyonda kullanılabilir ve sentetik ilaçlara karşı bitkisel alternatif oluşturabilirler.
INTRODUCTION: The Ferulago species are used as an aphrodisiacs in Turkey so we aimed to demonstrate in vivo and in vitro the relaxant effect of four Ferulago species extracts on corpus cavernosum (CC).
METHODS: A total of 30 adult male Sprague-Dawley rats were divided into control and diabetic group which were induced by single intraperitoneal injection of 40 mg/kg of Streptozotocin. In vivo erectile responses were utilized by the stimulation of cavernosal nerves and repeated after intracavernosal injection of extracts in rats and datas were expressed as intracavernosal pressure (ICP)/ mean arterial pressure (MAP) and total ICP. The relaxant and contractile responses of CC strips were analyzed in the presence or absence of extracts.
RESULTS: It was found that extracts were active both control and diabetic rats. The extracts (especially, methanol extract of root from Ferulago bracteata)-induced maximum relaxation responses (98.30 ± 2.6%) were decreased after incubation with L-NAME (44.8 ± 1.8). ODQ, soluble guanylate cyclase inhibitor inhibited 77% of extracts-induced maximum relaxation in CC from control rats.
DISCUSSION AND CONCLUSION: In conclusion these species can be utilized in erectile dysfunction and may exhibit a herbal alternative to synthetic drugs.
Abstract

10.Development and Optimization of Floating Multiparticulate Drug Delivery System of Norfloxacin
Rakesh Kumar Mishra, Tanaji Dilip Nandgude, Vaibhav Shivajirao Salve
Pages 326 - 334
INTRODUCTION: Norfloxacin is an synthetic broad-spectrum antibacterial drug having poor bioavailability and pH-dependent solubility. The purpose of present study was to develop gastroretentive floating multiparticulate drug delivery system of Norfloxacin.
METHODS: The Norfloxacin core pellets were prepared using microcrystalline cellulose (MCC) and polyvinylpyrrilidone K30 (PVP K30) by extrusion and spheronization technique. A 3-level, 3-factor, 17 run experimental box-behnken design was adopted to optimize levels of variables in the pellets formulations. The selected independent variables were amount of MCC, PVP K30, spheronizing speed and dependent variables were aspect ratio and hardness of pellets. Sodium bicarbonate and Hydroxyl Propyl Methyl Cellulose K15M in the ratio of 1: 1, 1: 2 and 2: 1 (w/w) on a dry solid basis was incorporated into Norfloxacin pellets and was further coated with EudragitRL100 using fluidized bed processor to obtain weight gain of 5%, 10% and 15% w/w.
RESULTS: Among the floating multiparticulate pellets batches, batch B-22 was found to be optimized based on the criteria of attaining minimum floating lag time (<10 minutes), and maximum value of drug released 82.11% in 8 hours. The percentage drug release for batch B-21 and B-23 was found to be 91.12% in 5 hours and 60.67% in 8 hours respectively. The drug release studies indicated that as the Eudragit RL 100 polymer coat increases the drug release gets decreased produces sustained release of Norfloxacin. The floating studies reveal that 70–90% of pellets remained floating for up to 8 hrs.
DISCUSSION AND CONCLUSION: The significant outcome obtained with the study indicates that such an approach can be effectively employed for improvement of bioavailability of drugs having poor absorption in lower part of the gastrointestinal tract with enhanced therapeutic efficacy.
Abstract

11.Impact of particle-size reduction on solubility and antidiabetic activity of extracts of leaves of Vinca rosea
Khalid Hussain, Abida Qamar, Nadeem Irfan Bukhari, Amjad Hussain, Naureen Shehzadi, Shaista Qamar, Sajida Parveen
Pages 335 - 339
INTRODUCTION: The present study aimed to enhance aqueous-solubility of methanol extract of leaves of Vinca rosea (Family: Apocynaceae) by particle-size reduction using milling, and evaluate its antidiabetic activity.
METHODS: The methanol extract (ME) was micronized using Vibratory Ball Mill, operated at vibratory speed of 15 Hz for 60 min, room temperature, and the resulting extract (MME) was investigated to determine particle-size, solubility, UV/Visible profile and in vitro antidiabetic activity.
RESULTS: The average particle-size of MME was found to be 0.753±0.227 µm which was less than half of the ME (2.007±0.965 µm). The solubility of MME was found to be greater than the ME. MME exhibited 65.63, 18.0 and 96.87% higher antidiabetic activity in the glucose uptake by yeast cells method, hemoglobin glycosylation assay and the alpha amylase inhibition assay, respectively (p < 0.05).

DISCUSSION AND CONCLUSION: The results of the present study indicate that micronization has effectively enhanced the aqueous solubility and antidiabetic activity of methanol extract of leaves of Vinca rosea.
Abstract

12.Design and in vitro evaluation of Eudragit-based extended release diltiazem microspheres for once and twice daily administrations: the effect of coating on drug release behavior
Noushin Bolourchian, Maryam Bahjat
Pages 340 - 347
INTRODUCTION: The aim of this investigation was to develop an extended release formulation of diltiazem hydrochloride (DL) for once and twice-daily administration, based on Eudragit (Eud) RL and RS microspheres using emulsion solvent evaporation method.
METHODS: Formulations with different drug-polymer concentrations were produced and characterized in terms of yield, encapsulation efficiency (EE), particle size and surface morphology. The drug release and thermal behavior of microspheres were also investigated. Selected microspheres were then coated with Eud RS by continuous solvent evaporation method, in order to modify the microspheres properties and burst release.
RESULTS: According to the results, the EE was in the range of 56-93 % for uncoated microspheres. The mean particle size of microspheres was different from 470 to above 1000 µm, based on various formulation variables. No difference was observed between the mean size of particles prepared with Eud RL and Eud RS. Microspheres showed sustained release behavior which was affected by drug: polymer ratio as well as particle size. Coating the microspheres not only improved the EE values (82-92 %), but also reduced the mean dissolution rate (MDR) and also the burst release.
DISCUSSION AND CONCLUSION: Microspheres prepared with DL: Eud RL ratios of 1: 3 and 1: 4, showed the release profiles in accordance with the USP criteria for DL extended release product, for dosing every 12 and 24 h, respectively.
Abstract

13.Formulation Design of Hydrocortisone Films for The Treatment of Aphthous Ulcer
Mohammed Gulzar Ahmed Mohammed, Sanjana Adinarayana Adinarayana
Pages 348 - 355
INTRODUCTION: Research and developments in oral drug delivery has evolved to changeover of solid dosage forms from tablets to oral films. These films offer an elegant route for systemic drug delivery, with the advantage for the patients who are suffering from the difficulty of swallowing larger oral dosage forms. Aphthous ulcers are the most common oral lesions which occurs as a round or oval, with a greyish yellow, crateriform base. For the treatment of aphthous ulcer various marketed product are available such as vitamin B12 tablet, benzydomine hydrochloride mouth wash or spray, steroid lozenges and local anaesthathatics. Hence hydrocortisone is selected as choice of drug for the treatment of aphthous ulcer which exhibits anti-inflammatory and immunosuppressant properties inhibiting the clinical manifestations.
METHODS: The main aim of the present study is to develop a hydrocortisone film in order to improve the therapeutic efficacy and bioavailability of hydrocortisone for the treatment of aphthous ulcer. The hydrocortisone film was developed containing various concentrations of methylcellulose and propylene glycol (0.25 - 2.0 %w/v) by solvent casting method. Prepared films were evaluated for various characterization studies like, film forming capacity, visual appearance, thickness, weight variation, folding endurance, surface pH, drug content, disintegration time, tensile strength, in vitro release study, ex-vivo study and stability studies.
RESULTS: Total eight formulations were developed out of that, formulation F2 (1.25%w/v) is considered as the optimized formulation as it showed the best results with respect to all characterization studies. The disintegration time (44sec) and maximum in vitro drug release i.e., 97.55% was observed. Further, no significant changes were observed during stability studies for the optimized formulation.
DISCUSSION AND CONCLUSION: From the study, it was concluded that hydrocortisone oral films can be formulated as a potentially useful tool for an effective treatment of aphthous ulcer with improved bioavailability, rapid onset of action and with increased patient compliance
Abstract

14.Investigation of gelatinase gene expression and growth of E. faecalis clinical isolates in biofilm models
Didem Kart, Ayşe Semra Kuştimur
Pages 356 - 361
GİRİŞ ve AMAÇ: Enterococcus faecalis biyofilm ilişkili enfeksiyonların ana sebebidir ve biyofilmlerde Staphylococcus aureus ile de etkileşimde bulunurlar. Jelatinaz (gelE) enzimi biyofilm oluşumunda E. faecalis için önemli bir virulans faktörüdür. Bu çalışma idrar ve üriner kateterlerden izole edilmiş biyofilm oluşturan E. faecalis izolatlarını karşılaştırmayı amaçlamaktadır. Aynı zamanda S. aureus’ un E. faecalis biyofilm hücrelerinin üremesi üzerindeki etkisi de in vitro iki türlü biyofilm modelinde incelenmiştir. Bir diğer amacımız biyofilm oluşumu sırasında E. facealis gelE gen ekspresyonunu değerlendirmektir.
YÖNTEM ve GEREÇLER: İzolatların total biyofilm biyokütlesinin ölçümünde ilk olarak kristal viyole boyama yöntemi kullanılmıştır. İkinci olarak, E. faecalis izolatlarının biyofilm oluşturma kapasitesini ve S. aureus’un E. faecalis biyofilmleri üzerinde etkisini değerlendirmek için plak sayım yöntemi uygulanmıştır. Son olarak, izolatların gelE ekspresyon profilleri qRT – PCR ile belirlenmiştir.
BULGULAR: Kristal viyole ve plak sayım yöntemine göre, tüm E. faecalis izolatlarının biyofilm oluşturdukları ve E. faecalis sesil hücre sayılarının S. aureus varlığında arttığı belirlenmiştir. Yirmibir E. facealis izolatı arasında, 10’u gelE gen ekspresyonunu yüksek oranda arttırmış, ancak 8’i azaltmıştır (P < 0.05).
TARTIŞMA ve SONUÇ: Birlikte üredikleri zaman; S. aureus, E. faecalis’e sesil hücre üremesini arttırmak gibi bazı avantajlar sağlayabilmektedir. GelE gen ekspresyonu idrar yolu enfeksiyonlu hastalardan izole edilmiş E. faecalis izolatlarının biyofilm oluşumundan etkilenmemiştir.
INTRODUCTION: Enterococcus faecalis is major reason of biofilm related infections and also interact with Staphylococcus aureus in biofilms. Gelatinase (gelE) enzyme is an important virulence factor of E. faecalis for biofilm formation. This study aimed to compare the biofilm producing E. faecalis isolates from urine and urinary catheters. Influence of S. aureus on the growth of E. faecalis biofilm cells was also investigated in a dual biofilm model in vitro. Another aim was to evaluate E. faecalis gelE gene expression during biofilm formation.
METHODS: Firstly, crystal violet staining was used to measure the total biofilm biomass of the isolates. Secondly, plate counting method was performed to determine the biofilm formation ability of E. faecalis isolates and the effect of S. aureus on E. faecalis biofilm formation. Finally, GelE expression profile of the isolates was assessed by qRT - PCR.
RESULTS: According to crystal violet staining and plate counting method, all E. faecalis isolates were found to be biofilm producers and the number of E. faecalis sessile cells were increased in the presence of S. aureus. Among 21 of E. faecalis isolates, ten of them expressed high levels of gelE gene, however eight of them had low expression profile (P < 0.05).
DISCUSSION AND CONCLUSION: When they grow up together, S. aureus may give some advantages to E. faecalis as increasing the sessile cell growth. The expression of gelE gene has not been affected by E. faecalis biofilm formation of the isolates collected from the patients with urinary tract infections.

Abstract

15.In Vitro Macrophage Nitric Oxide and Interleukin-1 Beta Suppression by Moringa Peregrina Seed
Shaymaa Fadhel Abbas Albaayit, Ahmed Salim Kadhim Al-Khafaji, Hiba Sarmed Alnaimy
Pages 362 - 365
INTRODUCTION: Moringa peregrina have long been used in folk medicine to treat diseases including fever, headache, burns, constipation, gut pains and inflammatory. Nitric oxide (NO) and interleukin-1 beta (IL-1β) play an important role in the pathophysiology of inflammation. The objectives of this study were to determine the effect of Moringa peregrina seed ethanolic extract (MPSE) on the viability of macrophages and NO and IL-1β production by lipopolysaccharide (LPS)-activated macrophage (J774A.1) cell line.
METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxic effect of MPSE treatment at concentrations ranging from 31.15 to 1000 µg/ml. The Nitric oxide concentration was determined by Griess assay and interleukin-1 beta proinflammatory cytokine concentration by enzyme-linked immunosorbent assay (ELISA) in the supernatant of Moringa peregrina seed ethanolic extract -treated lipopolysaccharide -activated J774A.1 cell culture. The statistical values were determined employing the statistical test of one-way analysis of variance.
RESULTS: Results: The results show that the Moringa peregrina seed ethanolic extract was not cytotoxic at 1000 μg/ml while significantly (p<0.001) inhibited Nitric oxide and interleukin-1 beta production by the lipopolysaccharide -activated macrophage J774A.1 cells.

DISCUSSION AND CONCLUSION: Conclusion: These findings suggest that the Moringa peregrina seed extract can be used to treat and prevent inflammatory diseases through the inhibition of inflammatory mediators. In spite of the fact that our findings was obtained by conducting an experimental research study, the outcomes, however, is promising and paving the way for foreseeable clinical prospective study.
Abstract

16.The influence of piperine on radioprotective effect of curcumin in irradiated human lymphocytes
Seyed Jalal Hosseinimehr, Nora Gheleshli, Arash Ghasemi
Pages 366 - 370
INTRODUCTION: Ionizing radiation (IR) induces DNA damage on normal cell leads to genotoxicity. The radioprotective effects of co-treatment curcumin and piperine were investigated against genotoxicity induced by ionizing radiation in human normal lymphocytes.
METHODS: Human blood samples were pretreated with curcumin at different concentrations (5, 10 and 25 µg/ml) and/or piperine (2.5 µg/ml) and then were exposed to IR at dose 1.5 Gy. The radioprotective effects of curcumin and piperine were assessed by micronucleus (MN) assay.
RESULTS: It was found that curcumin and piperine reduced the percentage of MN induced by IR in lymphocytes. Piperine alone significantly reduced genotoxicity induced by IR as compared to curcumin alone at all concentrations. An additive radioprotective effect was observed in combination of piperine and curcumin at low concentration 5 µg/ml while this synergistic effects were not observed with curcumin at higher concentrations 10 and 25 µg/ml.
DISCUSSION AND CONCLUSION: This result provides that piperine acts as a potent radioprotective effect at low concentration as compare to curcumin. However, an additive radioprotective effect was observed with co-treatment piperine and curcumin at low concentration, while piperine increased the percentage of MN in normal lymphocytes when was co-treated with curcumin at higher concentration.
Abstract

17.An overview of iQOS® as a new heat-not-burn tobacco product and its potential effects on human health and environment
Benay Can Eke, Rahman Başaran, Naile Merve Güven
Pages 371 - 374
Geleneksel sigaraların yanması sonucunda ortaya çıkan tütün dumanı nikotin, arsenik, benzen, karbonmonoksit, ağır metaller ve tütüne özgü nitrozaminler gibi birçok zararlı kimyasalı içermektedir. Tütünün yanmasıyla oluşan 7000’den fazla kimyasalın yaklaşık %1'i akciğer kanseri, kardiyovasküler hastalıklar ve amfizem gibi sigara içimine bağlı hastalıkların nedeni veya potansiyel nedeni olduğu bilinmektedir. Sigara içiminde tütünün yanması yerine ısıtıldığı sistemler, yirmi yıldan fazla süredir tasarlanmaktadır. “Heat-not-Burn” tütün ürünleri olarak bilinen bu ürünler, ilk kez 1988'de piyasaya çıkmış ancak ticari bir başarı sağlayamamıştır. Son 10 yılda, pek çok sigara firması tarafından yeni tasarımlı ısıtmalı tütün ürünleri yeniden piyasaya sürülmektedir. İlk kez Japonya ve İtalya’da tanıtılan I-Quit-Ordinary-Smoking (iQOS®) için modifiye edilmiş risk tütün ürünü olarak FDA’e başvurusu yapılmış fakat bu başvuru reddedilmiştir. Ancak günümüzde 41 ülkede halen satışı devam etmektedir. Geleneksel sigara ve elektronik sigara arasında melez bir ürün olarak kabul edilen iQOS®, tütünün yanmadığı ve 350 °C’ye kadar ısıtıldığı yeni teknolojisi ile geleneksel sigaralara kıyasla zararlı bileşenlerin seviyesinde önemli derecede azalma vaat etmektedir. Tamamen iQOS®'a geçiş yapan sigara içicilerinde birden fazla zararlı bileşene maruz kalma oranının azaldığı, iQOS® tarafından üretilen buharın sigara dumanından çok daha az toksik olduğu, iQOS® kullanımının iç hava kalitesini olumsuz yönde etkilemediği ve iQOS®’un pasif içicilik için bir duman kaynağı olmadığı konusunda bazı görüşler mevcuttur. Bu çalışmanın amacı, iQOS® üzerine yapılan bilimsel araştırmaların incelenerek, iQOS®’un insan sağlığı ve çevre üzerine etkilerini objektif bir şekilde ortaya koymaktır.
Tobacco smoke from regular cigarettes contains a number of harmful chemicals such as nicotine, arsenic, benzene, carbon monoxide, heavy metals, and tobacco-derived nitrosamines. About 1% of over 7000 chemical substances formed by burning tobacco are identified as the leading causes or possible risk factors of smoking-related diseases such as lung cancer, cardiovascular diseases, and emphysema. The concept of heating tobacco without combustion and smoke has been designed for more than two decades. The products developed with this idea, known as “Heat-not-Burn” tobacco cigarettes, were first introduced in the late 1980s but did not achieve commercial success. However, the tobacco giants have been trying to remarket the tobacco heating systems with new technological and modified features for over ten years. iQOS® (I-Quit-Ordinary-Smoking) is one of the latest heat-not-burn tobacco products that was first launched in Japan and Italy. The company then submitted to the FDA as a modified-risk tobacco product application to sell its own tobacco-heating device IQOS® under its Marlboro® brand in the USA with reduced-risk claims in 2016, but it was rejected. This device is, however, now sold in more than four dozen countries. There are some striking claims that iQOS® which is described as a novel hybrid product between traditional cigarettes and electronic cigarettes; offers an alternative way to substantially reduce the amount of harmful components compared with traditional cigarettes by its new technology in which tobacco is heated up to 350 oC instead of burning it; produces the vapor containing nearly 90 % less toxic substances than cigarette smoke; is not a source of secondhand smoking without negatively affecting indoor air quality. The purpose of this article is to objectively review the potential effects of iQOS® on human health and environment by searching and integrating the published research findings.
Abstract