Gözcü, Sefa; Akşit, Zeynep; Şimşek, Samed; Kandemir, Ali; Aydin, Ali; Yilmaz, Mustafa Abdullah; Akşit, Hüseyin

The study aimed to comprehensively identify the phenolic fingerprint of Morina persica L. (Caprifoliaceae) and evaluate its various biological activities. LC-MS/MS analysis of 70% Morina persica methanol extract revealed the presence of 27 phytochemicals, with quinic acid, chlorogenic acid, and rutin being the major phenolics. The antioxidant, antibacterial, antiproliferative, and cytotoxic activities were evaluated for biological screening. The results showed that the methanolic extract of M. persica has a moderate DPPH radical scavenging and ferric-reducing capacity, indicating antioxidant activity. M. persica was observed to have a sufficient antiproliferative effect against cancer cells and low cytotoxicity against normal cells. Moreover, M. persica demonstrated good antibacterial activity against Clostridium perfringens, Enterococcus faecalis, and Escherichia coli. These data suggest that the methanolic extract of M. persica could be considered both an industrial source of quinic acid and a potential biologically active ingredient for developing drug formulations.

Sezen, Selma; Ertuğrul, Muhammed Sait; Bayram, Cemil; Ökaraca, Mustafa; Koç, Taha Yasin; Demir, Abdussamed Yasin; Güllüce, Medine; Hacimüftüoğlu, Ahmet

Products from Mentha species are widely used in medical applications, including wound healing, due to the bioactive compounds they may contain. However, data on the effect of Mentha longifolia L. on wound healing are limited. This study investigated the antimicrobial and wound healing-promoting effects of Mentha longifolia L. essential oil using in vitro methods. The chemical compositions of the essential oil were identified using gas chromatography/mass spectrometry, while the agar well diffusion and disk diffusion methods were used to determine antimicrobial activity against pathogenic strains. A scratch wound healing assay was performed following determination of the cytotoxic dose in human fibroblast cell lines. The media were used for biochemical analysis 48 h after the in vitro wound model. Immunohistochemical staining was applied to determine the contribution of the essential oil to wound healing. The essential oil exhibited varying levels of antimicrobial activity against the tested pathogens and increased cell viability. All doses in the scratch wound healing assay promoted wound closure in a shorter time than in the control group. TAC levels were higher in the treated groups than in the control group, while TOS, IL-6, and TNF-α levels were lower. Levels of expression of FGF 2, IGF, and TGF-β were higher in the treated groups than in the control group at increasing doses. The essential oil of Mentha longifolia L. exhibited antimicrobial effects and improved wound healing at doses of 5 µg/mL and 10 µg/mL.

Ünal, Sedat; Polat, Heybet Kerem; Yuvali, Dönay; Köngül Şafak, Esra

In this study, cyclodextrin (HP-β-CD) inclusion complexes were prepared with Curcumin (CUR) by cosolvency/lyophilization method. Characterization studies were performed with phase-solubility diagrams, scanning electron microscopy (SEM), FT-IR, FT-Raman, XRD, Differential scanning calorimetry (DSC). The prepared CUR:HP-βCD complexes were evaluated for their anti-oxidant and anti-inflammatory activities compared to free CUR and significantly higher activity was detected with the complexation. In addition, pre-formulation studies have been completed in order to develop an in situ gel formulation, containing CUR:HP-β-CD, suitable for use in ocular diseases. To prepare the in situ forming gels, different Pluronic F127 (PF127) concentrations were used. Chitosan was added to the formulations to improve the gel's mucoadhesive properties. The formulations were evaluated for their viscosity pH, clarity, and sol-gel transition temperature. It was established that the formulations were all clear, their pH was 6, their gelation temperature decreased with increasing PF127, and was between 26-35 °C. Viscosities of all formulations were found to be suitable for ocular application. For the selected formulation, CUR and CUR:HP-β-CD were loaded to in situ gelling systems. In vitro release experiments revealed that the CUR:HP-CD inclusion complex including NSL formulation released for 6 hours with a higher burst effect than the other formulation. At the end of the study, in situ gel formulations containing CUR:HP-β-CD were successfully prepared and characterized comprehensively. In addition, a detailed release kinetic study was conducted for the formulations and it was determined that the CUR release from the in situ gel formulations was compatible with the Weibull model. In conclusion, a mucoadhesive in situ gel formulation containing anti-oxidant and anti-inflammatory CUR:HP-β-CD complex for ocular diseases is presented as an innovative formulation approach.

Polat, H. Kerem

This research aims to increase the solubility of Dexamethasone (Dex) using cyclodextrin and develop a temperature-triggered in situ gelling system for the ocular application. The solubility of Dex was increased with SBE-β-CD. Dex-SBE-β-CD inclusion complex was prepared with kneading and freeze-drying method. Structural characterization was carried out using DSC and FT-IR. When in situ gel formulations were prepared, Pluronic F127 (PF127), a thermosensitive polymer, and Chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer, were used together. When the solubility diagrams of the drug-cyclodextrin inclusion complex were examined, it was determined that SBE-β CD showed a linear increase, and AL-type diagram was selected in consequence. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. In situ gels were evaluated for clarity, pH, gelation temperature, and rheological behaviors and selected one formulation. It was established that the formulations were clear, their pH was 6, their gelation temperature decreased with increasing PF127, and was between 22-34 °C. For the selected formulation, 0.1% Dex and Dex/ SBE-β-CD were transferred to in situ gelling systems. As a result of in vitro release studies, it was observed that the release of the Dex/SBE-β-CD inclusion complex containing BRN formulation showed a higher burst effect than the other and was released for 6 hours. The results exhibited that the combination of PF127 and CH has potential as an in situ gelling systems for ocular delivery of Dex and Dex/ SBE-β-CD.

Bozbey, İrem; Önel, Gülce Taşkor; Türkmenoğlu, Burçin; Gürsoy, Şule; Dilek, Esra; Ergün, Muhammed; Özçelik, Azime Berna; Uysal, Mehtap

Alzheimer's disease is a neurological disease characterized by the destruction of brain cells. In this disease, which causes a decrease in thought, memory and behavioral functions, the symptoms appear gradually with age. In this study, inhibition of acetylcholinesterase enzyme which is an important target in accordance with the cholinergic hypothesis, was studied. New 3(2H)pyridazinone-triazole derivatives were synthesized, confirmed by1H-NMR,13C-NMR, HRMS analysis and their IC50 and Ki values were studied. The inhibition constants (Ki) of the compounds against the AChE enzyme ranged from 2.35 ± 0.18 to 5.15 ± 0.46 µM. The compound with the best inhibitory properties was compound 6d with a Ki value of 2.35 ± 0.18 µM. In addition, to support the experimental data, molecular docking studies were carried out with 6b, 6d, 6e and 6f compounds with AChE crystal structure (PDB ID:4M0E).

Polat, H. Kerem

Corneal neovascularization (CNV) is a serious ocular surface disease that causes the cornea to lose its transparent structure. It is a difficult disease to treat, so different drugs and different carrier systems are tried in the treatment of the disease. One of these methods is the combined application of metformin HCl (MHL) with a fluoroquinolone group antibiotic. The aim of this study is to load MHL with low permeability into a drug delivery system that can prolong the residence time on the ocular surface. In this context, different in situ gel formulations were produced by using poloxamer, a thermosensitive polymer, together with hydroxypropylmethylcellulose, a natural viscosity increaser. In situ gels were evaluated for clarity, pH, gelation temperature, and rheological behaviors and selected two formulation. After loading MHL and moxifloxacin HCl (MOX) into these two formulations, it was determined that they were clear, had a pH of around 7, a gelling temperature of 34-35 °C, and showed pseudoplastic flow. However, drug loading capacities were found to be over 97%.When in vitro release studies were examined, it was determined that both MHL and MOX released for at least six hours. The results showed that the combination of PF127 and HPMC has potential as an in situ gelling systems for ocular delivery of MHL and MOX.

Koçak, Engin; Özkul, Ceren; Taşkor Önel, Gülce; Nemutlu, Emirhan; Kir, Sedef; Sağiroğlu, Meral

Antibiotic resistance is one of the most serious global problems around the world. Pseudomonas aeruginosa is gram-negative bacteria and plays important role in local and systemic infections. In our work, we tried to understand mode of antimicrobial action of ferroccene-boronic acid over Pseudomonas aeruginosa via metabolomics and proteomics analysis. In proteomics analysis, we found that ferrocene-boronic acid effects various antimicrobial targets like ATP-dependent DNA helicase RecQ, Transcription-repair-coupling factor and Primasome assembly protein PriA. In metabolomics analysis, the ferrocene-boronic acid induced various metabolites involved in pyrimidine metabolism, lipid and fatty acid metabolism. Moreover, various polyamines like spermine and spermidine, which are very important for antibiotic resistance, pathogenesis and bacterial biofilm formation were decreased by ferroceneboronic acid. We believe that our results will contribute further studies regarding organometallic compounds in microbiology filelds.