Eczacılık Fakültesi / Faculty of Pharmacy
Permanent URI for this collectionhttps://hdl.handle.net/11727/5700
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Item Anti-Tyrosinase and Antimelanogenic Effect of Cinnamic Acid Derivatives from Prunus Mahaleb L.: Phenolic Composition, Isolation, Identification And Inhibitory Activity(2023) Guven, Zuhal Bayrakceken; Saracoglu, Iclal; Nagatsu, Akito; Yilmaz, Mustafa Abdullah; Basaran, A. Ahmet; 36924865; AAI-6606-2021Ethnopharmacological relevance: The traditional use of Prunus species against skin diseases and especially for skin lightning cosmeceutical purposes is widespread in many cultures. Prunus mahaleb L. is a well known food plant and used in the baking industry for flavoring. The fruit kernels (endocarp) are used in India for hyperpigmentation. Aim of the study: To investigate the chemical composition with the antimelanogenesis effect of P. mahaleb seed and kernel extracts and isolated compounds. Materials and methods: Isolation studies performed from the methanol extracts obtained from kernels and structures were determined using NMR and MS analysis. Antimelanogenesis effect was determined by mushroom tyrosinase assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells. Results: Five cinnamic acid derivatives were isolated and their structures (2-O-& beta;-glucopyranosyloxy-4-methoxyhydrocinnamic acid (1), cis-melilotoside (2), dihydromelilotoside (3), trans-melilotoside (4), 2-O-& beta;-glucosyloxy4-methoxy trans-cinnamic acid (5)) were elucidated using advanced spectroscopic methods. Mushroom tyrosinase enzyme inhibition of extracts, fractions and pure compounds obtained from P. mahaleb kernels were investigated and structure-activity relationship revealed. According to a detailed, comprehensive and validated LC-MS/MS technique analysis, vanilic acid (41.407 mg/g), protocatechuic acid (8.992 mg/g) and ferulic acid (4.962 mg/g) in the kernel ethylacetate fraction; quinic acid (14.183 mg/g), fumaric acid (8.349 mg/g) and aconitic acid (5.574 mg/g) were found as major phenolic compounds in the water fraction. The correlation of trace element copper content in extracts and fractions with mushroom enzyme activity was determined. By examining the enzyme kinetics of the compounds with effective cinnamic acid derivatives, inhibition types and enzyme binding constants Ki were calculated. Compounds 1,3 and 5 exhibited high noncompetitive tyrosinase inhibitory activity against L-tyrosine substrates, with IC50 values of 0.22, 0.31 and 0.37 mM respectively. In addition compounds 1, 3 and 5 showed dose-dependent inhibitory effects on intracellular tyrosinase and melanin levels in & alpha;-melanocyte-stimulating hormone (& alpha;-MSH)-induced B16F10 melanoma cells. Conclusions: Potent tyrosinase inhibitory compounds and extracts of P. mahaleb kernels suggest that it could be a new, non-toxic and inexpensive resource for the cosmeceutical industry and in skin diseases associated with hyperpigmentation.Item Evaluation of Possible Immunomodulatory Changes in Carbon Monoxide Poisoning(2023) Girgin, G.; Teksam, O.; Ozgunes, H.; Baydar, T.; Sabuncuoglu, S.Item Community Pharmacists Preparedness and Barriers for Cancer Health Promotion in North Cyprus(2023) Bosah, Dubem Henry; Birand, Nevzat; Basgut, Bilgen; https://orcid.org/0000-0002-5883-5583; 35234102; JKS-4834-2023Introduction The role of a community pharmacist is well recognized in the literature as the most accessible health care provider that promotes health wellness and disease prevention. Evidence supports their role in cancer health promotion though this is not seen yet in practice. The aim of the study was to assess community pharmacists' preparedness in terms of knowledge, role perception and barriers for providing cancer health promotion in North Cyprus. Methods A cross-sectional face-to-face questionnaire-based study was carried among a randomly selected representative sample of community pharmacists in North Cyprus between June 2020 and August 2020. A pre-validated 31-item questionnaire tool was revised by an expert panel and adopted for purpose of this study. Results 200 (64.5%) out of 310 approached community pharmacists' have accepted and responded to the questionnaire of which 183 were fully answered. The community pharmacists' awareness of cancer was moderate, as 70% answered correctly. Most respondents (93.4%) agree that pharmacists should be involved in cancer health promotion. Most respondents (> 90%) agree that pharmacist's lack of interest in oncology, lack of educational material and pharmacist's hesitancy about their knowledge of cancer are respectively the most important barriers for cancer health promotion. Conclusion The study shows that community pharmacist well perceives their role in cancer health promotion despite moderate awareness of cancer related facts and hesitancy of their knowledge necessary for assuming their role. Lack of interest, motivation and cancer educational materials availability are also major barrier to address.Item A Bayesian Estimation Framework for Pharmacogenomics Driven Warfarin Dosing: A Comparative Study(2015) Oztaner, Serdar Murat; Temizel, Tugba Taskaya; Erdem, S. Remzi; Ozer, Mahmut; 0000-0002-7537-2170; 25020183; AAJ-2370-2021The incorporation of pharmacogenomics information into the drug dosing estimation formulations has been shown to increase the accuracy in drug dosing and decrease the frequency of adverse drug effects in many studies in the literature. In this paper, an estimation framework based on the Bayesian structural equation modeling, which is driven by pharmacogenomics, is proposed. The results show that the model compares favorably with the linear models in terms of prediction and explaining the variations in warfarin dosing.Item Drug-related problems and health-related quality of life among chronic disease patients in a rural region of North Cyprus(2022) Goksin, Servet; Abdi, Abdikarim; Alsaloumi, Louai; Basgut, BilgenPurpose: To evaluate the various types of drug-related problems (DRPs) and health-related quality of life (HRQoL) among chronic disease patients in a rural region of North Cyprus.Methods: A cross-sectional study of patients visiting a rural community pharmacy in North Cyprus was conducted. Patient demographic information, quality of life (QoL), laboratory data, adherence, and beliefs about medicine were assessed using standardized tools. Drug-related problems were evaluated using PCNE V.9.1.Results: Among the 200 screened participants, 97 fulfilled the enrollment criteria and were interviewed. The median age of the participants was 62 years (interquartile range = 15), with 58.8 % women. Only 54 % of hypertensive (HTN) patients reached their target blood pressure level. Over 40 % of type 2 diabetes mellitus (T2DM) patients failed to achieve their target HbA1c level. The majority (71 %) of patients with HTN, T2DM or coronary artery disease were not compliant with lifestyle recommendations and 86.6 % had >= 1 DRP. Insufficient dosing and inappropriate indication for a drug were the DRPs associated with failure to achieve target and inappropriate drugs was the DRP type mostly associated with lower quality of life scores. Other factors associated with lower QoL levels included female gender, unemployment status, and high agreement with the statement "medications do more harm than good". Conclusion: Drug related problems and non-adherence are prevalent, while therapy targets are rarely met in rural Cyprus. Community pharmacists have the potential to improve outcomes in the management of non-communicable diseases (NCDs).Item Ritonavir Nanosuspensions Prepared By Microfluidization With Enhanced Solubility And Desirable Immunological Properties(2022) Karakucuk, Alptug; Canpinar, Hande; Celebi, Nevin; https://orcid.org/0000-0002-6402-5042; 35924723The objective of this study was to develop ritonavir (RTV) nanosuspensions (NSs) by microfluidization method. Particle size (PS) measurements were performed by photon correlation spectroscopy. Amorphous properties of the particles were evaluated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The dissolution studies were conducted in fed state simulated intestinal fluid (FeSSIF) medium. The flow cytometry was utilized to determine the lymphocyte sub-groups and immune response of NSs. RTV NSs were obtained with 400-500 nm PS. The crystal properties of RTV remain unchanged. The solubility of NS was enhanced five times. 57% and 18% of RTV were dissolved in FeSSIF medium for NSs and coarse powder. According to immunological studies, the prepared NSs did not significantly alter the ratio of CD4(+)/CD8(+). Therefore, NSs may be a beneficial approach for the oral administration of RTV.Item Cyclodextrin-Based Nanogel Of Flurbiprofen For Dermal Application: In Vitro Studies And In Vivo Skin Irritation Evaluation(2022) Oktay, Ayse Nur; Celebi, Nevin; Ilbasmis-Tamer, Sibel; Kaplanog, Guelnur TakeThe aim of this study was to develop and characterize flurbiprofen (FB)-loaded cyclodextrin (CD) based nanogel formulations for dermal application. Nanogels were produced via emulsification solvent evaporation and then incorporated into a hydroxypropyl methyl cellulose (HPMC) gel. The visual examination, pH, viscosity, dynamic rheological measurements and drug content analysis of nanogels were assessed. In vitro and ex vivo permeation, stability, and skin irritation were performed. pH of the FB-loaded nanogel and the nanogels in HPMC were 10.6 +/- 0.1 and 7.5 +/- 0.1 (neutral) respectively. The highest and lowest viscosities were observed in FB-loaded nanogels and in FB-free nanogels in HPMC, respectively. The tangent delta and storage modulus values of FB-loaded nanogel in HPMC were higher than those of FB-loaded nanogel. FB from nanogels in HPMC was 100% by 48 h. The final nanogel formulation was physically and chemically stable over 12 months. Skin irritation test showed no skin irritation or cellular infiltration on the histological level. In vitro and ex vivo permeation showed that the nanogels could be effective and stable formulations, especially in the dermal application of a hydro-phobic molecule.Item Test Performance Of Self-Report Adherence Tools In Patients With Hypertension: A Systematic Review And A Meta-Analysis(2022) Al-Alaili, Mohammed Khaled; Abdi, Abdikarim Mohamed; Basgut, Bilgen; 000888656300001What Is Known and ObjectivesAdherence has proved to have a positive influence on achieving plausible treatment outcomes. Self-report questionnaires are widely used in evaluating adherence, creating thus a high-powered research field. This review aims to provide an update of scales used in hypertension, which are compared and analysed against reliability and validity. MethodsPubMed, Web of Science and Cochrane Library were searched in May 2022 to identify studies. We extracted the study characteristics and evaluated their quality. A random-effects model with subgroup analysis was used to calculate estimates and heterogeneity parameters as well as regressions, funnel and forest plots. A bivariate model was selected to conduct validity analyses and draw receiver operating characteristic (ROC) curves. Results and DiscussionFifty-five articles were identified and classified into 22 different reliable and validated tools. Pooled analyses predicted an overall good Cronbach's alpha of 0.76 (95%CI:0.67-0.83), a good ICC of 0.8 (95%CI:0.72-0.86) and an excellent correlation coefficient of 0.91 (95%CI:0.86-0.95), which all showed high heterogeneity and slight detection of asymmetry. Regression analyses showed that only time and the number of items/scale type influenced significantly retest and alpha, respectively. Overall validity showed acceptable sensitivity of 0.65 (95%CI:0.53-0.75) and specificity of 0.57 (95%CI:0.47-0.67) with a good Area Under Curve (AUC) of 0.637. Upon comparison, four tools showed superiority over Morisky's scale. What Is New and ConclusionAdherence is a multi-dimensional phenomenon, which deems scales to be highly variable or complex; thus, complicating the selection process. Adherence to Refills and Medications Scale (ARMS) is the most promising free non-inferior alternative to Morisky, the most used scale.Item The Phytochemical Profile and Biological Activity of Malva neglecta Wallr. in Surgically Induced Endometriosis Model in Rats(2022) Akkol, Esra Kupeli; Karpuz, Busra; Turkcanoglu, Gizem; Cosguncelebi, Fatma Gul; Tastan, Hakki; Aschner, Michael; Khatkar, Anurag; Sobarzo-Sanchez, Eduardo; 000887409800001Leaves and aerial parts of Malva neglecta Wallr. have been traditionally used in Anatolia for the treatment of pain, inflammation, hemorrhoids, renal stones, constipation, and infertility. This study investigated the effects of M. neglecta leaves in a rat endometriosis model. The dried plant material was extracted with n-hexane, ethyl acetate, and methanol, successively. Experimental endometriosis was surgically induced in six-week-old female, non-pregnant, Wistar albino rats by autotransplant of endometrial tissue to the abdominal wall. After twenty-eight days, rats were evaluated for a second laparotomy. Endometrial foci areas were assessed, and intraabdominal adhesions were scored. Rats were divided into five groups as control, n-hexane, ethyl acetate, methanol, and aqueous extracts, as well as reference. At the end of the treatment, all rats were sacrificed and endometriotic foci areas and intraabdominal adhesions were re-evaluated and compared with the previous findings. Moreover, peritoneal fluid was collected to detect tumor necrosis factor- alpha (TNF-alpha), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) levels, and cDNA synthesis, and a quantitative real-time polymerase chain reaction (PCR) test was done. The phytochemical content of the most active extract was determined using High-Performance Liquid Chromatography (HPLC). Both endometrial volume and adhesion score decreased significantly in the group treated with methanol extract. In addition, significant decreases were observed in TNF-alpha, VEGF, and IL-6 levels in animals administered methanol extract. HPLC results showed that the activity caused by the methanol extract of M. neglecta was due to the polyphenols. Taken together, these novel findings indicate that M. neglecta may be a promising alternative for the treatment of endometriosis.Item Food plant with antioxidant, tyrosinase inhibitory and antimelanoma activity: Prunus mahaleb L(2022) Guven, Zuhal Bayrakceken; Dogan, Zeynep; Saracoglu, Iclal; Picot, Laurent; Nagatsu, Akito; Basaran, A. AhmetPrunus mahaleb L. seeds are used as spice and folk remedies in many countries. The aim of this study was bioactivity guided isolation and characterization phytoconstituents of P. mahaleb which have been studied very limited so far. The antioxidant capacities of seed and kernel (endocarp) extracts were studied by DPPH, nitric oxide (NO), superoxide (SO), TEAC, CUPRAC methods. The antiproliferative activity were investigated for the first time against B16F10, A2058, HeLa and L929 cell lines using MTT assay. Gallic acid and ursolic acid which have strong antioxidant and cell growth inhibitory effect, were isolated from the most active fractions. From the inactive fractions, quercetin-3-O(2-O,6-O-alpha-dirhamnopyranosyl beta-glucopyranoside), kaempferol-3-O(2-O,6-O alpha-dirhamnopyranosyl beta-glucopyranoside) and beta-sitosterol-3-O-beta-glucopyranoside were isolated. Our study is the first record for the isolation of ursolic acid from all parts of P. mahaleb, gallic acid from P. mahaleb kernels, two flavonol triglycosides from the Prunus species and their analysis by advanced NMR spectroscopic methods. Ursolic acid (IC50 : 170.2 mu M) and gallic acid (IC50 : 10.5 mu M) showed strong tyrosinase inhibition, gallic acid being 5.4 times more effective than standard compound. Kernel extracts have strong antioxidant activity, showed high growth inhibitory activity with dose-dependent manner on melanoma cells but no growth inhibitory on healthy L929 and HeLa cancer cells. The high antioxidant capacity of kernel, its selective growth inhibition of B16F10 and A2058 melanoma cells and its strong tyrosinase inhibitory compounds suggest that it could be a new, non-toxic and inexpensive resource for melanoma treatment and cosmetic industry.