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Background and Aims: Diazepam is accepted as a safer drug to medicate in many serious cases, acting as an anticonvulsant, an anxiolytic and a treatment for many types of poisoning. Monitoring it is important in achieving successful treatment and reducing the risk of toxic effects. In this study, it is aimed to develop and validate a sensitive, repeatable, and reliable method based on high-performance liquid chromatographic analysis for the determination in human plasma.Methods: Separation was carried out using a reverse-phase C18 column (4.0 mm x 150 mm, 3 μm) at 30 °C. The solution was prepared with a 10 mM phosphate buffer and acetonitrile (1:1, v/v) was employed as a mobile phase at the isocratic flow with 0.5 mL/min rate. Quantification was applied at 230 nm. A solid-phase extraction method was established and optimized, which was then used in the preparation of the plasma (0.5 mL) samples to the analysis.Results: The method was found to be linear (r2= 0.9805) between 100 and 1200 ng/mL. The analysis run was ≤12 min. Intra- day and inter-day accuracy were found between -5.78 and 5.93 and precision was ≤1.82%. The limit of detection and quan- tification were calculated as 20.42 and 61.86 ng/mL, respectively. Recovery was found between the range of 95.12% and 106.83%. The method was determined to be robust according to changes in UV, mobile phase organic solvent content, mobile phase pH, column temperature, and operator.Conclusion: This simple, sensitive and reliable method is suggested for accredited-reference laboratories working on the therapeutic drug monitorization and/or overdose-toxicological quantified analysis of diazepam in human plasma.

Background and Aims: Stachys L. species, which are members of the Lamiaceae family, have long been applied for their therapeutic benefits especially to cure cough, infection, genital tumors, ulcers, inflammatory illnesses, and wounds in Anatolian traditional medicine. In the current study, various extracts prepared from the aerial parts of Stachys cretica subsp. butgarica Rech.f. (SC), Stachys byzantina K. Koch (SB), Stachys thirkei K. Koch and were tested for their in vitro antioxidant, antibacterial, and anticandidat properties. Methods: The aerial parts of three Stachys species were sequentially extracted using n-hexane, chloroform, and methanol. Aqueous extracts of each sample was also prepared by infusion process. The total phenolic content of each extract was determined and the contribution of the biological activities in the samples was evaluated. To assess the antioxidant capacity, samples were studied using CUPRAC activity, DPPH center dot free radical scavenging, and FRAP methods. The antimicrobial activity of the extracts was tested against 7 bacteria and 3 yeast. Results: The infusion and methanol extract exhibited the strongest antioxidant potential and also had the highest percentage of phenolics among the studied extracts. The n-hexane extracts of all studied species showed considerable antifungal activity with MIC values ranging from 312.5-78.12 mg/L. Conclusion: According to our results, three Stachys species were found to be beneficial for their antioxidant and antimicrobial properties. Background and Aims: Stachys L. species, which are members of the Lamiaceae family, have long been applied for their therapeutic benefits especially to cure cough, infection, genital tumors, ulcers, inflammatory illnesses, and wounds in Anatolian traditional medicine. In the current study, various extracts prepared from the aerial parts of Stachys cretica subsp. butgarica Rech.f. (SC), Stachys byzantina K. Koch (SB), Stachys thirkei K. Koch and were tested for their in vitro antioxidant, antibacterial, and anticandidat properties. Methods: The aerial parts of three Stachys species were sequentially extracted using n-hexane, chloroform, and methanol. Aqueous extracts of each sample was also prepared by infusion process. The total phenolic content of each extract was determined and the contribution of the biological activities in the samples was evaluated. To assess the antioxidant capacity, samples were studied using CUPRAC activity, DPPH center dot free radical scavenging, and FRAP methods. The antimicrobial activity of the extracts was tested against 7 bacteria and 3 yeast. Results: The infusion and methanol extract exhibited the strongest antioxidant potential and also had the highest percentage of phenolics among the studied extracts. The n-hexane extracts of all studied species showed considerable antifungal activity with MIC values ranging from 312.5-78.12 mg/L. Conclusion: According to our results, three Stachys species were found to be beneficial for their antioxidant and antimicrobial properties. WOS:000744167900009

Background and Aims: Genus Veronica (Plantaginaceae) is represented by 79 species in Turkish flora, 26 of which are endemic. Veronica species have a variety of uses including diuretic, anticancer, and rheumatic pains, wounds, and respiratory problems. According to phytochemical studies, Veronica species contain predominantly iridoid glucosides with some phenylethanoid and flavonoid glycosides. Methods: The aqueous extract of Veronica peduncularis M.Bieb. was tested for its cytotoxic activity on human rhabdomyosarcoma (RD) and human epidermoid carcinoma (HEp-2) cell lines using the MTT method. Chemical profile of the extract was determined by HPLC-DAD, and isolation studies were conducted. Results: The extract was found to show concentration-dependent cytotoxicity against tested cell lines. In addition, a comparison of the iridoid fraction of Veronica peduncularis with previously isolated iridoid glucosides on the HPLC-DAD system, showed the presence of aucubin, amphicoside, veratroyl catalpol, and veronicoside in this fraction. On the other hand, isolation and structure elucidation of plantamajoside and 4'-O-methylisoscutellarein-7-O-2''-O-(6'''-O-acetyl-ß-D-allopyranosyl)- ß-D-glucopyranoside from the phenolic fractions were performed by serial chromatographic and spectroscopic methods. Conclusion: To the best of our knowledge, this is the first cytotoxic activity and phytochemical study on the titled plant. The presence of iridoid glucosides and 8-hydroxyflavone glycosides is important for the chemotaxonomy of the genus Veronica.

Background and Aims: Sideritis species (Lamiaceae) which are quite widespread in the Mediterranean region and represented by 46 species and 53 taxa in Turkey, are often used as a antirheumatic, anti-inflammatory, antimicrobial and diuretic remedies. Methods: In this study, the infusion (INF), essential oil (EO) and methanolic extract (ME) of chemical compounds prepared from aerial parts of Sideritis albiflora Hub.-Mor. (endemic) were investigated. Results: The presence of chlorogenic acid, verbascoside, forsythoside, apigenin glucoside, and isoscutellarein derivatives in the infusion and methanol extract of the plant was determined by LC-MS / MS analysis. In addition, the main constituents of the essential oil were found as germacrene D (23.5%), ß-caryophyllene (13.6%) and caryophylene oxide (8.0%) by GC / MS and GC / FID simultaneously. Conclusion: In this study, the essential oil, the methanolic extract and the infusion of S. albiflora species were prepared and their chemical compositions elucidated. It was determined that the essential oil chemical compound composition is rich in terms of the sesquiterpene group. Infusions of aerial parts of some Sideritis species have traditionally been used in the treatment of many diseases. Accordingly, the fact that the phenolic compounds of S. albiflora infusion have not been studied before increases the importance of this study. In addition, the therapeutic effect was shown to be related to major S. albiflora compounds, and the correlation between in vitro activity and ethnobotanical use was evaluated. The effective phenolic compounds contained in S. albiflora are thought to support the traditional uses of the plant.

Background and Aims: Nickel oxide nanoparticles (NiO-NPs) are one of the most used nanoparticles, especially as photosensitizers. Although some studies evaluate their toxicity in the liver, the information about their toxicity at the cellular and molecular levels is still controversial. In the present study, it was aimed to investigate the in vitro toxic potentials of NiO-NPs (average size 15.0 nm) in the liver (HepG2) cell Line. Methods: NiO-NPs were characterized by Transmission Electron Microscopy (TEM), the cellular uptake of NPs and the morphologic changes were evaluated by TEM and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), the cytotoxicity was evaluated by MTT and neutral red uptake (NRU) tests, comet assay was used for genotoxicity, Annexin V-FITC/propidium iodide (PI) apoptosis detection kit was used for apoptosis/ necrosis evaluation and Enzyme-Linked Immune Sorbent Assays (ELISA) kits were used for the potential of oxidative damage. Results: Our results showed that cellular uptake of NiO-NPs led to morphological changes in the cells, and caused cell death (1050 was 146.7 mu g/mL by MTT) mainly by apoptosis. Genotoxicity and oxidative damage were observed to be in a dosedependent manner. Conclusion: Results confirm previous data and draw attention to the toxic effects of NiO-NPs; further in vivo and in vitro studies need to be done to clarify the safety or toxicity of NiO-NPs. Research Fund of Istanbul UniversityIstanbul University [37785] This work was supported by the Research Fund of Istanbul University (Project No: 37785) .

Background and Aims: Nephrotoxicity is an adverse effect, which may occur with the use of tenofovir/lamivudine/efavirenz (TLE) in the treatment of human immune deficiency virus (HIV) infection. Curcumin (CUM), an isolate of Curcuma longa L. is used in folk medicine for the treatment of ailments. This study attempts to establish whether CUM supplementation can protect against a rat model of TLE-induced nephrotoxicity. Materials and Methods: Adult male Wistar rats (n=40) were randomly grouped and supplemented orally with CUM (50, 100 and 200 mg/kg/day) prior to the oral administration of TLE (300/300/600 mg/kg/day) for 30 days. After the treatment, the rats were fasted overnight, weighed and anesthetized. Blood samples were collected, and sera were extracted for biochemical analyses. Kidney samples were excised, weighed and processed for oxidative stress markers and histology. Results: Body weight was decreased (p

Background and Aims: The study was designed to evaluate the anti-fertility effect of methanolic extract of Clerodendrum serratum (MECS) on mature male rats. Methods: The vehicles and MECS were administered orally to four groups of forty male albino rats on consecutive days for 30 days. At the end of the experimental period, five animals from both the control and experimental groups were given anesthesia and the animal reproductive organs were collected and anti-fertility effect evaluated by studying the following parameters (i) Body and reproductive organ weight (ii) Biochemical estimation (iii) Reproductive hormone analysis (iv) Abnor malities in reproductive organ histology. Another five rats in each group were subjected to fertility testing. Results: This study shows that female rats which mated with MECS treated male rats delivered fewer pups than those which mated with the control rats. An antisteroidogenic effect was revealed through the increased concentration of testicular cho lesterol and ascorbic acid in MECS treated rats. However, testicular Δ5 -3β-hydroxysteroid dehydrogenase (Δ5 -3β-HSD), glucose-6-phosphate dehydrogenase (G-6-PD); serum reproductive hormones testosterone, FSH and LH were significantly reduced. Conclusion: The present investigation discovered the antisteroidogenic effect of MECS, which confirms the male antifertility effect of this plant. This encourages the traditional use of this plant in the Indian subcontinent as a male contraceptive.

Background and Aims: Prochloraz (PCZ) is an imidazole fungicide which is used in agriculture and gardening. PCZ, with endo crine disrupting effect, disrupts reproductive and developmental functions. Previously, the effects of PCZ on the estrogen and androgen receptors have been shown in vitro and in vivo. Because of endocrine disrupting effects, PCZ could influence nuclear receptors which acted as ER and AR antagonists. Besides, PCZ has been thought to have no genotoxic effects. Therefore, we aimed to investigate possible effects of PCZ on nuclear receptor genes and epigenetic mechanisms in human prostate carci noma (PC-3) cells. Methods: In the present study, MTT and LDH tests were applied to evaluate the cell viability. Expression levels of nuclear receptor genes such as AhR, PXR, PPARα, PPARγ were studied on real-time quantitative PCR. For global DNA methylation analysis, the levels of 5-methylcytosine (5-mC%) were measured by elisa kit. Results: According to MTT and LDH test results, IC50 value of PCZ has been determined as 144.19 and 116.65 μM, respectively. There were significant changes for the expression levels of AhR, PPARα and PPARγ genes after 5-50 μM of PCZ treat ments. 5 and 50 μM of PCZ decreased the levels of 5-mC% in the rates of 22.6% and 26.9%, respectively. Conclusion: It has been suggested that PCZ may cause alterations on the expressions of nuclear receptor genes which could be related to endocrine disrupting effects and may have implications on global DNA methylation.

Background and Aims: Melissa officinalis L. (lemon balm) is a perennial herb. Melissae folium and their preparations have been used for their sedative, spasmolytic and antibacterial actions. The study was aimed to investigate the qualities and also to compare the antioxidant activity potentials of the drug samples available in herbal markets and pharmacies in Turkey Methods: The percentages of the loss on drying and total ash were determined by gravimetric method and the percentage of total hydroxycinnamic derivatives was calculated by a spectrophotometric method according to European Pharmacopoeia. Drug samples were investigated for their potentials to scavenge the DPPH radical by using an in vitro method. Results: The percentages of the loss on drying were found to be between 8.51-16.53 %; whereas total ash amounts were determined between 9.41-11.33 %. The percentage of total hydroxycinnamic derivatives was found in the range of 4.45-12.97 %. The extracts of the samples were found to have DPPH radical scavenging activity with EC50 values ranging from 10.60 to 19.10 mu g/ml. Conclusion: In the assays for total ash and quantification of total hydroxy cinnamic derivatives all of the examined commercial samples were found to be compatible with standards in European Pharmacopoeia. Among the tested samples; a sample sold in pharmacy seems to have the best quality when its compared with the standards in European Pharmacopoeia., Ege University Re-search Fund [14-ECZ-009], This study was supported by Ege University Re-search Fund with the project number 14-ECZ-009.

Background and Aims: Many drugs with narrow therapeutic range and high toxicity risk are used in hematopoietic stem cell transplantation (HSCT) Units. The increase in the number of drugs raises the likelihood of interactions. This is particularly important in pediatric patients and may adversely affect the treatment process. In this study, we aimed to determine the potential drug interactions and to evaluate the clinical significance of them in terms of physician’s and pharmacist’s perceptions. Methods: The study was conducted as a prospective descriptive study over a six-month period in a tertiary care hospital’s Pediatric HSCT Unit. A pharmacist evaluated inpatients’ drugs for drug interactions by using a drug interaction checker program and the clinical significance of the interactions were evaluated by the physician and the pharmacist separately. Results: Drugs used in 20 patients (median age= 8 years, range= 0.6–17 years) were evaluated. A total of 525 potential drugdrug interactions were identified. Two hundred and forty seven interactions (47.05%) were major; 238 (45.33%) were moderate; 23 (4.38%) were contraindicated. The number of the interactions considered “clinically significant” by the pharmacist and “clinically insignificant” by the physician at the preparative regimen and post-transplant period were 15 (35.7%) and 37 (29.4%), respectively. Conclusion: The management of drug interactions is important in pediatric HSCT patients as a vulnerable group. Drug interactions should be interpreted according to the patient's clinical presentation, not only theoretically. Cooperation between physicians and pharmacists in the management of interactions will contribute to optimize the patient's treatment.

Background and Aims: Alzheimer's disease is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline. It is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as low levels of acetylcholine, deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, etc. Pharmacotherapy for this disease currently depends on using acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. They provide only symptomatic relief and mostly targets cognitive revival. Quinazoline derivatives were recently reported as being a valuable template in the treatment of many neurodegenerative disorders. Quinazoline based compounds were declared as being potential anti AD agents. This research focuses on the synthesis of novel quinazoline derivatives 3 and 4. Methods: Novel quinazoline derivatives 3 and 4 were synthesized starting from 2-(methylamino)benzamide by consecutive steps. The structures of these compounds have been characterized using different analytical and spectral methods: TLC, GC-MS, 1H-NMR and 13C-NMR. Results: This study revealed the synthesis of the novel compounds 3 and 4 with excellent yields equalling 97% and 73.1% respectively. Conclusion: Novel quinazoline derivatives compounds 3 and 4 were obtained. These compounds might be promising lead compounds for potential poly-functional anti-Alzheimer's agents in future work.

Background and Aims: Sulfonamide drugs are a very old and noted group of small molecules, and are still one of the most important antimicrobial compounds. In this study, starting from sulfonamide drugs, new original compounds containing frequent and functional rings such as thiazole and pyridine were synthesized and their antimicrobial effects were evaluated. Methods: Eighteen new compounds were synthesized by converting the 4-amino group of the sulfonamides to thiourea, and continued by thiazole ring closure. Characterization of the compounds was carried out by FT-IR, H-1-NMR and C-13-NMR and HRMS. MIC values were obtained in antimicrobial activity studies, which were carried out by Broth Microdilution method. Results: Compounds 3p-r had an effect of 32 mu g/ml against B. spizizenii. In addition, compounds 3d-f and 3p-r each showed effect against different gram-positive bacteria. Compound 3r had an MIC of 128 mu g/mL against gram-negative organisms. The rest of the series did not affect gram-negative bacteria. In the study, chloramphenicol and sulfamethoxazole were used as standards. Conclusion: Sulfanilamide and sulfadiazine derivatives showed higher inhibitory effects compared to the rest of the series. 3d-f and 3p-r showed inhibitor activity against gram-positive bacteria, conversely to the standard drug sulfamethoxazole, which possibly means that the mechanism of action is not same.

Background and Aims: Diabetes mellitus is characterized by hyperglycemia which over time leads to serious damage of several body systems. Vanadium ions and their complexes have been demonstrated to have various insulin-mimetic and antidiabetic effects. The object of the present work was to investigate the effect of vanadyl sulfate ( VS) on serum total lipid and protein parameters, glutathione, lipid peroxidation and nonenzymatic glycosylation levels in cardiac, lens, lung and skeletal muscle tissues of STZ diabetic rats. Methods: Randomly selected 6.0 - 6.5 month old Swiss Albino rats were separated into two diabetic and two control groups. A single intraperitoneal injection of 65 mg/kg streptozotocin (STZ) in 0.01 M citrate buffer (pH 4.5) was used to induce diabetes. 100 mg/kg VS was administered daily to one of the controls and one of the diabetic groups. On the 60th day of the experiment, serum total lipid and total protein levels were determined. Results: Tissue samples were taken and used for determination of glutathione (GSH), lipid peroxidation (LPO) and nonenzymatic glycosylation (GSH) and protein levels. Conclusion: According to the results, treatment with VS reversed the effects of diabetes by exerting antioxidant properties and preventing damage caused by diabetes on various tissues along with some serum parameters. Scientific Research Projects Coordination Unit of Istanbul UniversityIstanbul University [T-936/06112000] The Scientific Research Projects Coordination Unit of Istanbul University (Project number: T-936/06112000) supported this work.

Background and Aims: Alpha lipoic acid 600 mg HR film tablet showed high intra-subject variabilities in bioequivalence studies. In this regard, this study aims to determine whether Alpha lipoic acid 600 mg HR film coated tablet is a highly variable drug. Methods: First, a randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, two-way crossover oral bioequivalence study comparing the test product (Alpha lipoic acid HR film tablet - ILKO Pharmaceuticals, Turkey) with the reference product (Thioctacid®- Meda Pharma, Germany) was conducted in normal, healthy, adult human subjects under fasting conditions (Study 1). Secondly, a randomized, open-label, balanced, two-treatment, four-period, two-sequence, single-dose, fully replicate crossover oral bioequivalence study was conducted in normal, healthy, adult human subjects under fasting conditions (Study 2). Results: Study 1 failed. It had a 90% confidence interval for LnCmax (ng/mL) value between 79.69% – 138.98% with a high intra-subject coefficient of variability (ISCV=57.5%). In study 2 a 90% confidence interval for LnCmax (ng/mL) was found between 88.40% – 129.81% while the ISCV value for LnCmax was 64.5%. Conclusion: The findings suggest that bioequivalence study for Alpha lipoic acid HR film tablet should be redesigned since this is a highly variable drug. Therefore, conventional bioequivalence acceptable limits (80.0%-125.0%) should be adjusted to 69.84% – 143.19% for alpha lipoic acid.

Background and Aims: It has been observed that the combined treatment of esomeprazole and pirfenidone provides increased efficacy in the treatment of pulmonary fibrosis disease, recently. The aim of this study is to develop a simple, sensitive, and reliable high-performance liquid chromatography method to be used in drug monitoring to increase the effectiveness of esomeprazole and pirfenidone in treatment and to reduce their adverse effects. Methods: Separation was conducted with a C18 reverse-phase column (4.6 mm x 250 mm, 5 mu m) used as a mobile phase prepared with the phosphate buffer (10 mM KH2PO4 and 10 mM K2HPO4) and acetonitrile (60:40, v/v) by an isocratic flow (1 mL/min). Mobile phase pH was adjusted to 3.0. Ultraviolet detection was accomplished at 305 nm. The column oven was held at 35 degrees C to ensure an efficient analytical separation. Results: Analytical recovery of esomeprazole was between 92.43 and 105.36% and for pirfenidone it was found between 89.56 and 104.32%. Accuracy values of esomeprazole and pirfenidone were determined between (-2.90) - 4.22 and (-4.45) - 5.78, respectively. Precision (RSD%) was

Background and Aims: The main purpose of this study is to determine the molecular structure and isomers of the new 1-methyl 5-trifluoromethoxy-1H-indole-2,3-dione 3-[4-(4-methoxyphenyl)thiosemicarbazone] (5) and to prove the 3Z-conformer of the compound 5. Methods: The molecular structure of E- and Z-isomer mixture 5 was confirmed by analytical and spectral data (UV, IR, 1 H NMR, HSQC-2D and MS). The Z-conformer of compound 5 was characterized by NMR spectroscopy and X-ray single crystal diffraction analysis method (SC-XRD). Results: The compound 5 was synthesized by condensation of 1-methyl-5-trifluoromethoxy-1H-indole-2,3-dione (2) with 4-(4-methoxyphenyl)thiosemicarbazide (4). The compound 5 was obtained in two separate forms, crystal and amorphous. It was proved by NMR data and X-ray diffraction findings that the crystal form is the Z-isomer and the amorphous form is a mixture of the E- and Z-isomers. The E- and Z-isomer ratios were determined by 1 H NMR spectroscopy. The crystal structure and molecular interactions of the Z-conformer were determined by X-ray single crystal diffraction analysis. Conclusion: In the crystal, three intramolecular N—H···N, N—H···O and C—H···S hydrogen bonds provided isomer formation. Also, molecular packing was stabilized by intermolecular C—H···O hydrogen bonds, the π-π stacking interactions and weak CO···π (ring) contacts.

Background and Aims: Dengue fever is a major health concern, especially in developed countries, because it often leads to undifferentiated febrile illness such as dengue haemorrhagic fever and dengue shock syndrome or expanded dengue syndrome, which are often reported with thrombocytopenia (TCP) and turn out to be hazardous to life. The WHO reported 23 million dengue cases and 82,000 deaths between 1955-2012. 2019 was a hallmark for the dengue epidemic from Latin America to South Asia. Due to unavailability of a dengue vaccine and antiviral therapies, additional medical attention and effort are required to treat thrombocytopenia (TCP). These approaches include thrombopoietin receptor agonists such as Oprelvekin, Eltrombopag, Romiplostim and corticosteroids, and platelet transfusion and intravenous immunoglobulin transfusions. The outcomes might not be achievable unless the proper assessment is carried out to evaluate these approaches to treat TCP in dengue patients. This narrative review aims to summarize the findings regarding the treatment of TCP in patients affected by the dengue virus. Methods: A total of 55 published articles, including clinical trials, descriptive studies and case studies were reviewed regarding treatment of TCP in the context of dengue infection. The electronic databases PubMed, Cochrane Library, Google Scholar and Science Direct were searched for articles published from January 1990 to June 2020. Conclusions: We concluded that dengue fever is becoming a global health concern. Premedical attention like the use of corticosteroids, Thrombopoietin receptor agonist (TPO-R) agonists and transfusions like (PT & IVIG) are not fully assessed by double-blind randomized clinical trials and cost-effectiveness analysis. However, as compared to other treatment approaches, the use of TPO-R agonists seems to be more suitable in TCP management due to its easy access and compliance.

Background and Aims: Consolida orientalis (J.Gay.) Schrödinger belonging to the Ranunculaceae family, which is called “morçiçek” in Turkey. It can be recognized by its laciniae linear leaves, intense violet flower, and follicle fruit. The aim of the present study is to elucidate the anatomical properties of C. orientalis, as one of the medically important plant species of Ranunculaceae family. Methods: Plant material was collected from Kahramankazan (Ankara-Turkey). The samples were protected in 70% alcohol. The transverse and surface sections were investigated by light microscope and photographed. Results: The root is characterized by a periderm, pericyclic sclerenchymatous ring, and vessels embedded in sclerenchymatous pith cells. It was observed that in the anatomical features of the stem, the adaxial walls of epidermis cells curved outward and were covered with a thick cuticle layer. Moreover, stomata were observed in the epidermis and the stem had hairs only at the above parts, while other parts were bare. These hairs consisted of both glandular (with a long stalk) and non-glandular (unicellular, silicified) types. The leaf is broadly v-shaped, monofacial and has a 1-layer epidermis. Ranunculaceous stomata and non-glandular (unicellular, silicified and slightly bowed) hairs were observed on both surfaces. Conclusion: The root, stem, and leaf anatomy of C. orientalis was studied for the first time. The anatomical features described in detail with reference reports could be helpful in future taxonomic studies.

Background and Aims: Ballota is represented by 12 species and 16 taxa in Turkey. Eleven of the 16 taxa are endemic to Turkey. Ballota have been used in different treatments in folk medicine. Antiinflammatory drugs act by protecting lysosomal membrane integrity or inhibiting enzymes of prostaglandins and thromboxane inflammatory mediators synthesized by deactivating of cyclooxygenase (COX), COX-1 and COX-2 enzymes. Besides, degradation of lysosomal membrane brings on the release inflammatory mediators so human red blood cells (HRBC) can be used for evaluating of antiinflammatory activity. One of the treatment approaches of diabetes mellitus is α-glucosidase enzyme inhibition. These enzymes play an important role in glucose releasing from carbohydrates. Due to the adverse effects of synthetic drugs, natural α-glucosidase inhibitors have been discussed as therapeutic agents to manage diabetes mellitus. In the light of the traditional use of Ballota species, we aimed to investigate the antiinflammatory and antidiabetic activities of the ethanol and aqueous extracts from the aerial parts of 14 Ballota taxa. Methods: HRBC membrane stabilizing and α-glucosidase inhibitory methods are used for determining antiinflammatory and antidiabetic activities of 14 Ballota taxa, respectively. Results: According to our results, the ethanolic extracts showed higher membrane stabilization profile than aqueous extracts generally. And for antidiabetic activity, it is concluded that aqueous and ethanol extracts of Ballota glandulosissima exhibited the maximum α-glucosidase inhibitory activity. Conclusion: According to our results, IC50 values of antiinflammatory effect of ethanolic and aqueous extracts of 14 Ballota samples ranged from 4,30-12,88 and 3,18-20,25 mg/ml, respectively. It is observed that aqueous extracts of Ballota nigra subsp. anatolica exhibited the maximum antiinflammatory effect. Both aqueous and ethanol extracts of Ballota glandulosissima are found to exhibit the maximum α-glucosidase inhibitory activity with IC50 values of 2,18 and 2,30 μg/ml, respectively. Among the ethanolic extracts of Ballota species, the strongest α-glucosidase inhibitory activities are found as B. glandulosissima>B. cristata>B. saxatilis subsp. brachyodonta in descending order.

DOI: 10.26650/IstanbulJPharm.2018.414805In this study, the cytotoxic effects of1H-indole-2,3-dione 3-[N-(4-sulfamoylphenyl)thiosemicarbazone derivativesnamely, 4a-d were evaluated using cell kinetic parameters including the cellindex, mitotic index, labelling index and apoptotic index on HeLa cells takenfrom a human cervix carcinoma. All compounds were evaluated using cell indexparameters at 5, 10, 20, 40, 80, 100 and 160 μM concentrations. As a result ofthis, it was seen that all 4a-d compounds were effective in differentconcentrations. Different cell death mechanisms were proposed for 4a-d. Whenall the parameters were examined, it was found that the bromine substituted 4cwas the most potent antiproliferative compound in the tested compounds. Thedifference was significant between the control and experimental groups(p

DOI : 10.26650/IstanbulJPharm.2018.18007 In this study, with intent to find out novel anti-biofilm and antiviral agents, a series of amide derivatives were synthesized and their structures were elucidated by FT-IR and 1H-NMR and 13C-NMR and MS methods. And also, their purity were proven by TLC, HPLC and elemental analyses. And finally, the synthesized compounds were examined for their biofilm formation and swarming motility inhibitory activities in P. aeruginosa PA01. These compounds were found to reduce biofilm formation by 8.7-25.6% and swarming motility by 18.3-33.8% in P. aeruginosa PA01 at a concentration of 200 μM. Besides, all of the compounds were evaluated for their antiviral activity against influenza A viruses. The plaque inhibition assays indicated that compound 6 (N-(4-{[5-(ethylamino)-1,3,4-thiadiazol-2-yl]methyl}phenyl)-4- fluorobenzamide) has considerable inhibitory effect on influenza A virus plaque formation.

DOI : 10.5152.IstanbulJPharm.2018.397094 A high performance liquid chromatography method has been developed for determination of letrozole in tablets. The method has developed in reverse phase column with acetonitrile-50.0 mM phosphoric acid solution, pH:7 (50:50, v/v) and 0.7 mL/min flow rate by using a fluorimetric detector. Letrozole has natural fluorescence properties, and there is no need for derivatization for this molecule. The detector was set at 256, 585 nm for excitation and emission wavelength respectively. The method was validated in accuracy, precision, specificity, linearity and system suitability parameters are studied. The linear range was found 50-700 ng/mL. The limit of detection and quantification for letrozole was found to be 14-50 ng/mL respectively. The recovery of drug is found to be 98.8%. The developed method has been validated and successfully applied to tablet analysis of drug substance. This method is simple, reproducible and can be used safely for routine analysis of letrozole in tablets.

DOI: 10.5152/IstanbulJPharm.2018.416835 In this study, a reversed-phase, high pressure liquid chromatography (RP-HPLC) method was applied in the quantitative analysis of lycorine in the aerial parts and bulbs of Galanthus alpinus Sosn. var. alpinus collected from Rize during the flowering and fruiting seasons. A simple method to extract lycorine from the plant specimens was performed, using pre-packed columns with diatomaceous earth (Extrelut®). The chromatographic separation was achieved employing an isocratic system with a mobile phase including trifluoroacetic acid-water-acetonitrile (0.01:95:5) measured at a flow rate of 1 mL/min using a diode array detector (DAD). The lycorine content in the bulbs during the flowering and fruiting seasons was detected as 0.01576 and 0.02351 %, respectively. Also, validation studies showed that the method was specific, accurate and precise.

DOI: 10.5152/IstanbulJPharm.2018.410411 The genus Scorzonera (Asteraceae) has several species which are used as a vegetable and in folk medicine all around the world. A phytochemical study was carried out on petroleum ether fraction of methanol extract obtained from the roots of Scorzonera veratrifolia Fenzl (Bitlis / Turkey) to investigate the terpenoid composition of the plant. Column chromatography, preparative thin layer chromatography and gas chromatography (GC) were used for separation of the compounds. Their structures were determined by using GC-MS and NMR techniques. Seventeen triterpenoids (s-amyrin, s-amyrin acetate, s-amyrinone, germanicol, germanicol acetate, germanicone, α-amyrin, α-amyrin acetate, α-amyrinone, ψ – taraxasterol, ψ – taraxasterol acetate, taraxasterol, taraxasterol acetate, lupeol, lupeol acetate, lupenone, fern-7-en-3-one) and one sterol (s-sitosterol) were determined. The presence of these compounds has been shown for the first time in S. veratrifolia. α-amyrinone, s-amyrin, s-amyrinone, ψ – taraxasterol and ψ – taraxasterol acetate are new for the genus Scorzonera.

DOI : 10.5152/IstanbulJPharm.2018.412321 Turkey has a rich plant diversity due to its geography and many of these plants are used in the treatment of various diseases. The usage of these medicinal plants has been passed down from generation to generation. Ethnobotanical studies are used to record traditional treatment methods and this information is intended to contribute to drug development studies. This study (which is the fourth article in a series focusing on plants with painkilling properties) details the plants used to combat toothache. In this survey, which was prepared by screening ethnobotanical research, a total of 52 taxa were traditionally used in toothache treatment in Turkey. Scientific and local names, families, parts used, and treatment methods of these plants were recorded. According to the results of the research, the most common families are Lamiaceae, Asteraceae, Solanaceae, Euphorbiaceae, Liliaceae and Rosaceae. The most commonly used taxa in different regions of Turkey are Cornus mas, Dianthus zonatus var. zonatus and Hyocyamus niger. These plants contain analgesic and anti-inflammatory compounds. These plants are usually used externally as extracts (infusion/decoction) as well as are used directly. However, a few species are also used externally.

DOI: 10.26650/IstanbulJPharm.2019.18008Medicinal plants have been widely used infolklore medicine in the treatment of various diseases such as mental andneurological disorders. Mental disorders like anxiety and depression are verycommon among Nigerian populace. The purpose of this review was to access andevaluate several articles published on the anxiolytic and sedative propertiesof medicinal plants in Nigeria and to find out the gaps left for furtherresearch and drug development. Eighty-two publications available among NigerianUniversities and Research Institutes between 2008 and 2018 were selected. Sevenelectronic databases such as Nigerian Plant Database, HerbMed, AGRICOLA,MedlinePlus, PubMed, ScienceDirect, and Springer-Link were thoroughly exploredfrom which 226 relevant articles were obtained using Google Scholar, Hotbot andFreeFullPdf as search engines. A number of studies conducted to test for theanxiolytic and sedative activity of medicinal plants in Nigeria were included.Articles published between 2008 and 2018 were selected. The studies wereconducted in Nigeria. Research carried out before 2008 was not selected. Allpublications with authorship outside Nigeria were excluded. Several medicinalplants on which experiments were conducted were reported to have anxiolytic andor sedative properties in Nigeria. Several medicinal plants have shown promiseas anxiolytic and sedative agents in laboratory animals’ studies. The majorityof these plants were used traditionally in the past to treat anxiety inNigeria. Further research on the efficacy and safety of these medicinal plantscould yield a more cost effective and perhaps safer alternative in thetreatment of anxiety among Nigerians. Cite this article as: Abubakar AR, Haque M(2019). Medicinal plants with reported anxiolytic and sedative activities inNigeria: A systematic review. Istanbul J Pharm 49 (2): 92-104.

CECEN, Omer/0000-0002-1315-9876, WOS: 000484810700006, Chemical composition of volatile oils obtained from the roots, fruits and aerial parts of Glaucosciadium cordifolium (Boiss.) B. L. Burtt& P. H. Davis (Apiaceae) were analyzed using gas chromatography-flame ionization detector/mass spectrometry, simultaneously. Furthermore, antimicrobial and antioxidant activities of G. cordifolium volatile oils were investigated for possible utilization. Total of 62 volatile compounds were identified in G. cordifolium essential oils, where the main component was characterized as alpha-pinene in all parts, commonly. the other main components were beta-pinene (15.7%), (Z)-beta-ocimene (14%) and sabinene (7%) in the volatile oil of the aerial part; sabinene (10.1%), beta-pinene (10.1%) and alpha-phellandrene (5.3%) in the essential oil of the fruits; hexadecane (12.2%), tetradecane (11.9%), octadecane (7.4%) in the essential oil obtained from the root, respectively. the in vitro microdilution method was used for the antimicrobial activity testing against Salmonella typhi ATCC 6539, Acinetobacter baumanii ATCC 19606, Bacillus cereus ATCC 14579, Staphylococcus aereus ATCC 6538, Listeria monocytogenes ATCC 19115, Helicobacter pylori ATCC 43504 and Mycobacterium avium ATCC 25291. the best antimicrobial activity of the volatile oils was against L. monocytogenes among the tested microorganisms. in addition, DPPH center dot-ABTS(center dot) scavenging activity was tested, none of the essential oils showed any significant antioxidant activity.

DOI : 10.26650/IstanbulJPharm.2019.435408 In this research, five propolis samples collected from Turkey were investigated to observe the correlation between botanical sources and chemical contents of the samples and in this way emphasize the influence of botanical sources of propolis on its chemical characterization. As a first step, to determine the botanical sources of the samples, microscopic analysis was performed. According to the microscopic analysis results; two samples that were collected from Rize (P1 and P2), were characterized as most probably being chesnut propolis; while one sample collected from Tekirdag (P3) was evaluated as being a mixed type, in the other Tekirdag sample (P4), the pollens belonging to the taxa of the Brassicaceae family were found as dominant. The sample collected from Sivas (P5); was also recognized as mixed type. The second step of the research was the chemical analyses of the propolis samples. According to the results; the balsamic contents of the propolis samples ranged between 59.97 and 83.31%, total phenolic contents were ranged between 27.56±0.05 and 171.93±0.28 mgGAE/g. The minimum flavone and flavonol content of 0.28±0.01% was found in the P1 sample described as chesnut propolis and colected from Rize. The maximum value 5.1±0.07% was found in the P4 sample as was total phenolic content. Flavanones and Dihydroflavonols contents varied between 6.58±0.009-12.94±0.007%. According to the GC-MS results the investigated samples contained compounds belonging to the various groups. With regard to the Excel correllation, the balsamic content showed a negative correlation with total phenolic content, flavone and flavonol content, flavanones and dihydroflavonols content. Cite this article as : Gencay Celemli O, Atakay M, Sorkun K (2019). The correlation between botanical source and the biologically active compounds of propolis. Istanbul J Pharm 49 (2): 81-87.

DOI : 10.26650/IstanbulJPharm.2019.418892 Callistemon citrinus is a member of Myrtaceae family that thrives under different ecological conditions. The leaves, flowers, stem backs and roots of the plant contain various phytochemicals that are useful in folk medicine for different remedies such as antimicrobial, anti-nociceptive, fungicide and anti-inflammatory purposes. In this study, we investigated the cytotoxic effect of Callistemon citrinus leaf and flower methanolic extracts against human Colo-205 Cell Line using real time cell analyzer device for monitoring in time-dependent manner. To determine the mechanism of cytotoxicity of the extracts, Western blotting assay was used for measuring evocation of Akt pathway. Extracts were found to exert cytotoxic effect at a dose dependent manner. IC50 values of leaves and flowers extract were 6.49 µg/mL and 5.22 µg/mL, respectively. At the early stages of the experiment, Akt pathway was triggered at high extract concentrations. Although, high extract concentrations showed proliferative effect at early stages, this effect reversed after 5 and 8 h resulting in low cell viability. Findings from this study therefore showed that extracts of leaf and flower from Callistemon citrinus demonstrated cytotoxic effect against Colo-205 but seems not to be related Akt signaling pathway. Cite this article as : Dokumaci AH, Fayemi PO, Aycan Yerer B. (2019). Real time monitoring of cytotoxicity of Callistemon citrinus against Colo-205 cell line. Istanbul J Pharm 49 (1): 25-32.

Background: Following cardiovascular diseases, cancer is the world's second leading cause of death. Chemotherapy is the conventional gold technique for successful treatment of cancer. There are some drawbacks associated with traditional chemotherapy, namely, low aqueous solubility, limited biological half-life, production of multidrug resistance and non-specificity (lack of targeting ability) or dose-limiting cellular toxicity. To develop a targeted drug delivery for its anticancer effect is still a challenging task. Methods: We developed literature review methods which included inclusion and exclusion criteria for identifying potentially relevant articles, articles search strategies, abstract review protocols and a comprehensive scoring system for published studies. This study contains a detailed survey of various reported methods such as folic acid-drug conjugates, Cobalamin- Drug Conjugate, Vitamin B12-Conjugated and Paclitaxel-Loaded Micelles etc., all of which were studied for their methods of preparation and possible impact on biological activity. Results: Due to its specific ability to carry anticancer drugs directly to tumours, vitamin-mediated drug targeting has recently emerged as a novel concept. Solid tumour cancer has an unquenchable appetite for various essential vitamins, resulting in over-expression of the receptors involved in cell internalization of vitamins on the surface of cancer cells. So, the vitamin drug conjugates are specifically important for carrying the anticancer drugs directly to the tumour cells. Biotin, folic acid, vitamin B12 and riboflavin, the vitamin necessary for the division of all cells, especially cancer cells, have recently been examined as targeting agents. Conclusion: Vitamin-Drug Conjugate methods were found to be the most suitable methods amongst all the other reported methods and they can be applied for current therapy against cancer.

Background and Aims: Occurence of the mycotoxin citrinin could increase during Monascus purpureus fermentation in red yeast rice resulting in contamination of meat products when the red yeast rice is used as food additive. The aim of this study was to investigate extraction of citrinin from meat products by different extraction methods including LLE, QuEChERS and IAC methods. Methods: Because of high sensitivity IAC method was selected for the extraction of citrinin in 33 meat products (salami, sausage and minced meat), then citrinin was analysed by HPLC- FLD. Results: IAC method was linear in the range of 0.25-100 ng/g (r2 ≥0.999) in meat products. Citrinin was found at 0.28 to 1.79 ng/g in 6 of the 19 samples (36.84%); and in one sausage sample contained citrinin at LOD level. However, citrinin was not detected in the salami and minced meat samples. Conclusion: Our results indicated that citrinin in meat products could be an important health concern. Since no limits were set in food products, regulations should be developed concerning the presence of citrinin in other products as well as meat products, in Turkey.

Background and Aims: Dental plaque as the main etiological factor for caries and periodontal disease is transparent, colorless and not easily visible. Visualized dental plaque can be an aid for patients to develop an efficient system of plaque removal. Several disclosing agents have been developed and applied to clinical and home-care use, yet people are still searching for a natural coloring agent which could be considered safe for long term use. Methods: In this study, various concentrations of Pitaya flesh extract were tested to stain dental plaque taken from 30 volunteers. A disclosing agent of basic-fuchsin already marketed was used as a positive control. The dental plaque specimens were divided into 5 groups and each group was randomly stained either with 0.05 mL of basic fuchsin as a positive control, or 25%, 50%, 75%, or 100% Pitaya flesh extract. The specimens were then analyzed using a spectrophotometer. Results: The results showed that Pitaya flesh extract exhibited dental plaque staining ability. The concentration of 75% Pitaya was similar to the staining ability of basic-fuchsin, while 100% was superior to that of basic-fuchsin. Conclusion: Under the limitations of this study, 75% and 100% extract of pitaya flesh exhibited dental plaque staining in vitro as assessed by a spectrophotometer.

Background and Aims: The use of natural polymers as wound dressings is attracting more interest due to their favoured properties such as biodegradability and biocompatibility. With this background, chitosan films and chitosan/pectin polyelectrolyte complex films encapsulating silver sulfadiazine were fabricated as novel wound dressings. Methods: Films were fabricated, and the surface topography and the surface roughness of the films were characterised by atomic force microscopy. Swelling and hydrolytic degradation behaviours of the films were monitored, and surface chemistry analysis was carried out. Following drug release studies, release kinetics were studied to evaluate the films for drug delivery. Results: Results suggest that the characteristic crystalline structure of chitosan films disappears after complexation with pectin. Polyelectrolyte complex films were found to be more durable than chitosan films due to their improved resistance to hydrolytic degradation. No incompatibilities amongst formulation components were detected. In vitro drug release studies indicated a rapid release of the drug from chitosan films compared to polyelectrolyte complex films. Conclusion: The overall results suggest that chitosan/pectin polyelectrolyte complex films have improved properties in terms of durability compared to chitosan films. Both films could be a promising candidate for wound healing applications considering the specific needs of different types of wounds.

Background and Aims: Adenosine deaminase (EC 3.5.4.4, ADA) is distributed in all human tissues. It catalyses the deamina tion of adenosine (deoxyadenosine) to inosine (deoxyinosine) via removal of an amino group. The determination of ADA-inhibition is of extreme significance in the field of fundamental research and clinical diagnosis. In our study, the effects of various plant extracts and chemicals on ADA activity were investigated. Methods: Adenosine deaminase activity was determined spectrophotometrically at 625 nm. Results: The inhibitory activities of the extracts and chemical compounds increased in a dose-dependent manner. Among the plant extracts used, lemon extract was observed to exhibit the highest ADA inhibition activity with an IC50 value of 0.05 +/- 0.001 mg/ml, while quercetin had the highest ADA inhibition (IC50 value of 0.004 +/- 0.0005 mg/mL) among the chemical compounds. All plant extracts and chemical compounds showed ADA inhibition activities. Conclusion: The obtained results indicate that plant extracts and some chemical compounds examined in this study can be a potential source of novel ADA-inhibitors for therapeutics.

Background and Aims: The main aim of the study was to enhance the cognitive function of the brain by nootropic herbal formulations in animal models. Polyphyto herbal formulations were known to enhance the cognition and memory function by several pathways such as anti-oxidative, anti-inflammatory, and cell signaling pathways. In this study, six formulations were prepared by mixing specified plant parts and were coded as NHF1, NHF2, NHF3, NHF4, NHF5, and NHF6. Methods: The potency of the formulations was assessed by In vivo (photo actometer, rod walking test, pole climbing test, and Ellman’s acetylcholinesterase test) studies. Results: NHF1 and NHF5 exhibited greater activity than the standard drug donepezil in vivo (Ellman’s acetylcholinesterase test) analysis. NHF1 and NHF5 formulations containing plant parts were further investigated against several published literatures for the identification of chemical constituents and those chemical constituents were subjected to molecular docking and in silico ADME prediction studies to figure out the possible compounds responsible for the cholinesterase inhibition activity. Conclusion: In conclusion, the computational studies also reveal that presence of chemical constituents such as sarsasapogenin (13.13 nM), racemosol (16.26 nM), and beta-sitosterol (30.47 nM) having binding energy (-10.75 kcal/mol), (-10.63 kcal/mol), (-10.25 kcal/mol), might be directly responsible for the nootropic activity.

Colorectal cancer (CRC) comprisesapproximately 10% of all cancers and is a major cause of cancer-relatedmorbidity and mortality despite current diagnostic and treatment improvements.DNA damage and altered DNA replication through the deregulation of relatedgenes cause genomic instability in sporadic CRC. DNA repair is very complex;many factors play a role to ensure that the restoration of errors occurs duringthe transfer of genetic material. MutL homolog 1 (MLH1) is one of the vital DNArepair genes responsible for genomic stability. Together with environmentalfactors, the genetic background may be associated with CRC development; thus,genetic polymorphisms are considered as risk factors. The present prospectivecase–control study aimed to determine the association between 93G>A andI219V polymorphisms of MLH1 and CRC susceptibility in a Turkish population. Thegenotyping of 158 patients and 164 age- and sex-matched controls was performedby polymerase chain reaction-restriction fragment length polymorphism. Twovariants, 93G>A and I219V, were associated with an increased risk of CRC.Individuals with A allele of 93G>A had an approximately 2-fold risk (OR:1.92, 95% CI: 1.22–3.04; p

Pharmacists are supposed to know current issues in social sciences and techniques to understand diseases and illnesses, to empathize with patients and other health professionals, to resolve possible conflicts of interest, to establish an ideal communication, to ensure the rational use of drugs, to reduce the wastage of drugs, and to improve compliance with drug therapy. The purpose of this article was to explain the conceptual framework of the Health Belief Model and Functional Health Literacy, which are recently outstanding topics on healthcare. Further, Pharmacotherapy Literacy is going to be defined as a remarkable subject in the literature. This is a descriptive study illustrating the concepts with the literature.

This paper reports folk medicinal and food plants of Nizip (Gaziantep) located in the south part of Turkey. The purpose of the study is to gather, determine, and record the plants that are used as source of food and medicine by local people. The information was obtained from participants in face to face interviews; furthermore, the specimens of the plants were collected. Voucher specimens were deposited at the Herbarium of the Faculty of Pharmacy, Marmara University. Totally, twenty-seven plants are recorded as used as traditional folk medicine for the region, and thirteen of these are also used as a source of food. Among them, 20 taxa were wild and 7 taxa were cultivated plants. According to the majority of the plants which have similar usage, the plants are mostly used for gastrointestinal, respiratory system diseases and diabetes.

Recently, because of the rising in multidrug resistance from infectious agents, there is a prompted interest for the development of new antimicrobial agents and new therapeutic strategies to combat the infections caused by the resistant bacteria. Among them, the natural bactericidal compounds, such as antimicrobial cationic peptides (AMPs) seems very promising agents. AMPs are the important component of the innate immune response to the surrounding microorganisms. This substances which can be isolated from most of the living organisms, have various activity like broad spectrum antibacterial, antifungal, antiviral, and antiprotozoal. However there are some resistance mechanisms that affects the AMPs, because of the rapid action and existing more than one mechanism of action, development of resistance to AMPs is quite rare. Due to their many advantages and characteristics, AMPs looks like a good candidate for being a new generation, active antimicrobial agent for antimicrobial chemotherapy against especially multi drug resistant bacteria and biofilms, either alone or in combination.

The objective of this study was to develop a chewing gum formulation for benzydamine hydrochloride (BN) and evaluate the effect of different co-compression agents on physicochemical parameters and in vitro drug release profile. BN has been utilized in symptomatic treatment for pain and irritations of the mouth and throat. Chewing gum formulations of BN were produced using direct compression method. In fabricated chewing gums, except pharmacopeia analysis, physical and structural analysis like thickness, weight variation, elasticity and compressibility were evaluated. The release of BN from the gum was studied using the chewing apparatus which have been designed for procuring the release of BN from the chewing gum.The quantity of BN present in the chewing gum and the release medium were quantified by spectrophotometric method. Gum formulations showed promising in vitro release profiles, in which 80–90% BN was released in a sustained manner over 20 min of chewing time. In addition, it was observed that the drug release was fitted into matrix diffusion kinetic and revealed a non-Fickian drug release mechanism. This study suggests that BN in a gum formulation is a suitable dosage form for the delivery in the oral cavity, thereby and serving as an instant analgesic.

Local plant names vary in Anatolia in every settlement. Ethnobotanical studies help to record local names of the used plants that may otherwise be lost to future generations. This study is the part of an ethnobotanical study which was conducted between 2012 and 2015 in order to determine wild plants used in Kepsut and Savaştepe (Balıkesir, Turkey). Kepsut and Savaştepe are the towns of Balıkesir province in the Marmara region of Turkey. As a result of the identification, the 509 local names of the 265 taxa, which are 12 of them are endemic, belonging to 72 families were recorded. According to the literature, among 509 local names, 338 local names were recorded for the first time in Balıkesir.

Human populations are exposed to several toxic substances in the environment, including pesticides. Fenoxaprop-p-ethyl (FPE) and fluzifob-p-butyl (FPB) herbicides are extensively used in agricultural fields due to their high target selectivity and low non-target toxicity. They are known as aryloxyphenoxypropionate herbicides, and acetyl-CoA carboxylase inhibitor. In the study, we aimed to evaluate the toxic potentials of FPE and FPB herbicides. Cell viability was evaluated by MTT assay in the range of 15.6-500.0 μM exposure concentrations in mouse fibroblast (BALB/3T3) cell line. Also, we investigated their DNA damage potentials on BALB/3T3 cells by using alkaline Comet assay. The results indicated that FPE and FPB showed no evidence of DNA damage. And, the cell viability was more than 20% at 12.5-400 μM exposure concentrations. FPE and FPB might be safe according to our results and the previously studies, and there would be public health benefits from encouraging its use in the place of more toxic herbicide products.

DOI : 10.26650/IstanbulJPharm.2019.19020 Bismuth (III) oxide nanoparticles’ (Bi2O3-NPs) unique physicochemical properties attracted the attention in biological, industrial, technological and medical fields. Concurrently, increasing numbers of studies revealing their potential toxic effects and possible toxicity mechanisms are ongoing. In this study, we assessed the toxic potentials of Bi2O3-NPs in human SH-SY5Y neuroblastoma cell line. After Bi2O3-NPs characterization using TEM, the cytotoxic potentials were evaluated by MTT and LDH assays. The induction of reactive oxygen species production was evaluated by H2DCFDA. In order to evaluate the oxidative damages, the changes in antioxidant catalase and superoxide dismutase and glutathione levels were determined. The cellular death pathway and the role of immune response were studied by measuring the mRNA expression levels of related genes. Our results showed that Bi2O3-NPs decreased the cell viability through disruption on mitochondrial activity (IC50:77.57 μg/mL) and membrane integrity (LDH%50:16.97 μg/mL). At 50 μg/mL Bi2O3-NPs, the production of reactive oxygen species (ROS) was induced significantly as well as the catalase and superoxide dismutase levels. In immune response, the mRNA expression levels of interleukin (IL)-6 were increased more than 1.5-fold in all doses; whereas, TNF-α, NF-ĸB and MAPK8 expressions were remained unchanged. Consequently, Bi2O3-NPs induced oxidative stress-related inflammation via activation of pro-inflammatory cytokine, IL-6. You may cite this article as : Oztas E, Abudayyak M, Aykanat B, Can Z, Baram E, Ozhan G (2019). Bismuth Oxide Nanoparticles Induced Oxidative Stress-Related Inflammation in SH-SY5Y Cell Line. Istanbul J Pharm 10.26650/IstanbulJPharm.2019.19020.

Rheum ribes is a perennial herbaceous plant belonging to the Polygonaceae family that grows more in rocky and gravelly slopes in high altitude areas of Levant and Turkey. Rheum ribes is consumed as food and widely used in folk medicine against nausea, constipation and for different diseases including diabetesand hypertension. Unfortunately, the researches on Rheum ribes toxicity are insufficient. In our study, human hepatocellular carcinoma (HepG2) cell line was used in cytotoxicity evaluation of Rheum ribes water, methanol and chloroform extracts by MTT and NRU test. Comet assay was used to investigate the genotoxicity potentials of the plant extracts. Our results show that all extracts cause cell death in a concentration dependent manner at 5-50 mg/mL concentrations. The IC50 values are 14.29- 31.94 mg/mL by MTT and 21.15 - 27.66 mg/mL by NRU assay. The highest concentration (25 mg/mL) of methanol extract causes a significant DNA damage (8.7-folds). In conclusion, similar to a lot of plants used in the folk medicine the risk of Rheum ribes is still unknown. The uncontrolled use of this plant could harm to the patients. Our results indicate possible cyto- and gentoxicity effects of Rheum ribes, these results should rise the concerns about the safety of Rheum ribes and other folk herbs. Cite this article as : Abudayyak M (2019). In vitro evaluation of Rheum ribes induced genotoxicity in HepG2 cell lines. Istanbul J Pharm 10.26650/IstanbulJPharm.2019.19021.