Browsing by Author "Oner, Erkan"

Now showing 1 - 6 of 6

Can Quercetin Reduce Arsenic Induced Toxicity in Mouse Balb/C 3t3 Fibroblast Cells ? A Study Involving in Vitro, Molecular Docking, and Adme Predictions
(Bmc, 2025) Unsal, Velid; Keskin, Cumali; Oner, Erkan
This study aimed to investigate the protective effect of quercetin against arsenic-induced oxidative damage, inflammation, and apoptosis in mouse BALB/c 3T3 fibroblast cells (NIH-3T3). Arsenic at different concentrations of 0.05 mu M (low), 0.5 mu M (medium), 10 mu M (high) doses were used to induce toxicity, while 120 mu m quercetin was used for treatment. MTT and LDH analyses were performed to determine the effect of arsenic and quercetin on cell viability, while oxidative stress markers and antioxidant enzyme activities were measured by spectrophotometric method. TNF-alpha and IL-1 beta levels were measured by the ELISA method, Autodock programs were used for molecular docking studies. In addition, computer-based analyses of quercetin and succimer molecules were performed using SwissADME web tools. TNF-alpha (PDB ID: 2AZ5), IL-1 beta (PDB ID: 1ITB), Caspase3 (PDB ID: 2XYG), Bax (PDB ID: 4S0O), SOD (PDB ID:1CBJ), GSH-Px (PDB ID: 1GP1) and Bcl-2 (PDB ID: 1G5M) crystal structures were obtained from the Protein Data Bank. Bax and Bcl-2 levels of apoptotic genes and mRNA expression levels of Caspase-3 activity were measured using the QRT-PCR technique. TUNEL staining was performed to determine DNA fragmentations, while DAPI staining was done to visualise nuclear modifications. Quercetin has been found to significantly reduce oxidative stress, inflammation, and apoptosis in cells and exert anti-apoptotic effects. Molecular docking studies revealed quercetin shows good binding affinity with molecules with SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-alpha and IL-1 beta structures, and has been observed to bind with Bax and Bcl-2 with molecular docking scores of -7.5 and - 7.7 kcal/mol, respectively. These findings are supported by results showing that quercetin is effective in anti-apoptotic and anti-inflammatory processes in arsenic-induced cells under in vitro conditions. In addition, when ADME values are examined, it can be considered that quercetin is a useful and effective candidate compound in reducing arsenic toxicity, considering its higher synthetic accessibility score, better pharmacokinetic properties, and good biological transition and interaction capacities compared to succimer.
Comparison of New Secondgeneration H1 Receptor Blockers With Some Molecules; a Study Involving Dft, Molecular Docking, Admet, Biological Target and Activity
(Bmc, 2025) Unsal, Velid; Oner, Erkan; Yildiz, Resit; Mert, Basak Dogru; Yıldız, Reşit; Unsal, Velid
Although the antiallergic properties of compounds such as CAPE, Melatonin, Curcumin, and Vitamin C have been poorly discussed by experimental studies, the antiallergic properties of these famous molecules have never been discussed with calculations. The histamine-1 receptor (H1R) belongs to the family of rhodopsin-like G-protein-coupled receptors expressed in cells that mediate allergies and other pathophysiological diseases. In this study, pharmacological activities of FDA-approved second generation H1 antihistamines (Levocetirizine, desloratadine and fexofenadine) and molecules such as CAPE, Melatonin, Curcumin, Vitamin C, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) profiles, density functional theory (DFT), molecular docking, biological targets and activities were compared by calculating. Since drug development is an extremely risky, costly and time-consuming process, the data obtained in this study will facilitate and guide future studies. It will also enable researchers to focus on the most promising compounds, providing an effective design strategy. Their pharmacological activity was carried out using computer-based computational techniques including DFT, molecular docking, ADMET analysis, biological targeting, and activity methods. The best binding sites of Desloratadine, Levocetirizine, Fexofenadine, CAPE, Quercetin, Melatonin, curcumin, Vitamin C ligands to Desmoglein 1, Human Histamine H1 receptor, IgE and IL13 protons were determined by molecular docking method and binding energy and interaction states were analyzed. Fexofenadine and Quercetin ligand showed the most effective binding affinity. Melatonin had the best Caco-2 permeability PPB values of Quercetin, CAPE and Curcumin were at optimal levels. On the OATP1B1 and OATP1B3 of curcumin and CAPE, Quercetin was found to have strong inhibition effects on BCRP. Melatonin and CAPE were found to have the highest inhibition values on CYP1A2, while CAPE had the highest inhibition values on CYP2C19 and CYP2C9. Vitamin C and Quercetin were found to be safer in terms of cardiac toxicity and mutagenic risks, while Desloratadine and Levocetirizine carried high risks of neurotoxicity and hematotoxicity, while CAPE was noted for its high enzyme inhibitory activities and low toxicity profiles, while the hERG blockade, DILI, and cytotoxicity values of other compounds pointed to various safety concerns. This study demonstrated the potential of machine learning methods in understanding and discovering H1 receptor blockers. The results obtained provide important clues in the development of important strategies in the clinical use of H1 receptor blockers. In the light of these data, CAPE and Quercetin are remarkable molecules.
Comparison of Pde-5 Inhibitors Used in Erectile Dysfunction With Some Candidate Molecules: a Study Involving Molecular Docking, Admet, Dft, Biological Target, and Activity
(Bmc, 2025) Sagir, Suleyman; Unsal, Velid; Oner, Erkan; Yildiz, Resit; Mert, Basak Dogru
Erectile dysfunction (ED) is a urological condition defined as the inability of a man to achieve or maintain an erection. This condition negatively affects his sexual performance and the performance of his partner. Phosphodiesterase type 5 (PDE5) inhibitors are commonly used to treat ED. Arginase II plays an important role in regulating L-arginine to NO synthase in the smooth muscle of the human corpus cavernosum of the penis. NO is a molecule essential for regulating a variety of functions, including arterial blood pressure, penile erection, and energy balance. Substances such as vardenafil, alprostadil, papaverine, and resveratrol increase NO production, thereby supporting sexual function and vascular health. Additionally, NO donors such as L-arginine, L-citrulline, and alpha-lipoic acid provide effective alternatives when used in combination with PDE5 inhibitors. Medications used in the treatment of ED include vardenafil, alprostadil, and papaverine. In addition, although molecules such as L-arginine, citrulline, resveratrol, alpha-lipoic acid, and rutin are thought to play a role in ED, their pharmacological and molecular effects have not been sufficiently elucidated. The aim of this study was to investigate the effects of these molecules in the treatment of ED by computer-based calculations, to obtain new information about them and to inspire new treatment strategies for ED. The physicochemical, molecular and pharmacokinetic properties of the compounds were determined by SwissADME software, and ADMET (absorption, distribution, metabolism, excretion and toxicity) data were determined by ADMETlab 3.0 software. Biological target and activity data were obtained by MolPredictX and PASS Online software. While the Gaussian 09 program was used for DFT calculations, PyMOL, AutodockTools 4.2.6, AutoDock Vina, and Biovia Discovery programs were used for molecular docking studies. It was found that L-arginine, citrulline, resveratrol and alpha-lipoic acid were well absorbed from the intestine, while rutin showed limited absorption. When their metabolic risks were evaluated, L-arginine and citrulline were found to have lower toxicity. Molecular docking results of rutin and resveratrol were remarkable. The electronic properties of the compounds were explained by DFT calculations. L-arginine and citrulline were found to have low toxicity and positive therapeutic effects. L-arginine and citrulline stand out as promising candidates for future research. Although resveratrol data are promising, unfortunately their potential toxicity and metabolic interactions require further investigation. It is important to learn more about these compounds or conduct research to improve their therapeutic efficacy. Although computer-based calculations play an important role in toxicity predictions, drug interactions, pharmacokinetics and toxicity properties should be carefully evaluated.
Evaluation of Extra Virgin Olive Oil Compounds Using Computational Methods: in Vitro, Admet, Dft, Molecular Docking and Human Gene Network Analysis Study
(Bmc, 2025) Unsal, Velid; Yildiz, Resit; Korkmaz, Aziz; Mert, Basak Dogru; Caliskan, Cemile Gunbegi; Oner, Erkan; Yıldız, Reşit; Unsal, Velid; Korkmaz, Aziz
This study investigates the phenolic compounds (PC), volatile compounds (VC), and fatty acids (FA) of extra virgin olive oil (EVOO) derived from the Turkish olive variety "Sar & imath; Ulak", along with ADMET, DFT, molecular docking, and gene network analyses of significant molecules identified within the EVOO. Chromatographic methods (GC-FID, HPLC) were employed to characterize FA, PC, and VC profiles, while quality parameters, antioxidant activities (TAC, ABTS, DPPH) were assessed via spectrophotometry. The analysis revealed a complex composition of 40 volatile compounds, with estragole, 7-hydroxyheptene-1, and 3-methoxycinnamaldehyde as the primary components. Hydroxytyrosol, tyrosol, oleuropein, apigenin, ferulic acid, and vanillic acid emerged as main phenolic constituents, with hydroxytyrosol and apigenin exhibiting high bioavailability. Molecular docking highlighted oleuropein and pinoresinol as compounds with strong binding affinities, though only hydroxytyrosol, apigenin, and pinoresinol fully met Lipinski and other drug-likeness criteria. DFT analysis showed that oleuropein and pinoresinol have notable dipole moments, reflecting polar and asymmetrical structures. KEGG enrichment analysis further linked key molecules like oleuropein and apigenin with pathways related to lipid metabolism and atherosclerosis, underscoring their potential bioactivity and relevance in health-related applications.
Evaluation of Oxidative Stress Biomarkers in Patients with Henoch-Schönlein Purpura
(Folia Medica, 2021) Unsal, Velid; Temiz, Fatih; Dalkıran, Tahir; Kandur, Yasar; Kurutas, Ergul Belge; Unsal, Velid; Oner, Erkan
Introduction: Henoch-Schönlein Purpura (HSP) is a systemic vasculitic syndrome characterized by non-thrombocytopenic purpura, arthritis/arthralgia, abdominal pain, and glomerulonephritis. The pathogenesis of HSP has not been clearly identified. Oxidative damage has a role in the pathogenesis of most cases. Aim: This study aimed to evaluate changes of oxidative stress by studying parameters like superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in an attempt to identify the role of oxidative stress in HSP from another perspective. Materials and methods: This study enrolled 23 pediatric patients (ten girls and thirteen boys) diagnosed with HSP who were under follow-up at Sutcu Imam University School of Medicine Department of Pediatrics between 2014 and 2016 and twenty healthy children as the control group. The parents of all subjects gave informed consent to participate in the study. In the HSP group, the beginning season of the illness and the systemic involvement during follow-up were determined. Blood specimens were obtained at presentation before any treatment was started. SOD, CAT activities, and MDA values in erythrocyte and plasma samples were compared between the patient group and the healthy children. Results: Twenty-three patients with HSP (13 males, 10 females) and 20 healthy children participated in this study. The mean age of the HSP cases was 8.21±3.78 years (range 2-16 years) and of the controls was 8.6±4.2 (range 3-14 years). The mean MDA value was 2.95±0.71 nmol/ml in the patient group and 2.67±0.66 nmol/ml in the control group (p=0.787). The mean level of the CAT enzyme was 1.32±0.35 U/g Hb in the patient group and 7.8±1.74 U/g Hb in the control group (p=0.001). The mean levels of the SOD enzyme were 3.06±0.85 U/g Hb in the patient group and 0.97±0.36 U/g Hb in the control group (p=0.001). Conclusions: Although high MDA levels support the role of lipid peroxidation in the pathogenesis of HSP, statistical significance was not reached owing to a limited number of our patients. The reduced CAT enzyme activity is consistent with the findings of previous reports. This finding supports the notion that oxidative stress can play a role in the pathogenesis of HSP.
Morin Attenuates Arsenic-Induced Toxicity in 3t3 Embryonic Fibroblast Cells by Suppressing Oxidative Stress, Inflammation, and Apoptosis: in Vitro and Silico Evaluations
(Oxford Univ Press, 2024) Unsal, Velid; Aktepe, Necmettin; Aktepe, Necmettin; Oner, Erkan
This study aims to investigate the curative effects of Morin, a flavonoid, against arsenic toxicity in 3T3 embryonic fibroblast cells and its effect on the molecular mechanisms of cells. The cytotoxicity and viability of the cells were measured by MTT and LDH tests. Arsenic (0.74 mu M) was used to trigger toxicity and Morin (50 mu M) was used for treatment. The levels of oxidative stress biomarkers and the activities of antioxidant enzymes were measured by spectrophotometric method, and inflammatory markers were measured by ELISA method. While mRNA expression levels of Bax, Bcl-2 levels, and Caspase-3 activity were measured by qRT-PCR technique, TUNEL staining was performed to detect DNA breaks and DAPI staining to visualize nuclear changes. Protein structures were retrieved from the protein data bank. OpenBabel and Autodock programs were used for the molecular docking study. Morin rescued the 3T3 embryonic fibroblast cells exposed to arsenic. However, Arsenic decreased the activities of antioxidant enzymes in cells and significantly increased oxidative stress, inflammation, and apoptosis. Morin treatment reduced oxidative damage and TNF-alpha and IL-1 beta levels. Arsenic-induced Caspase-3 mRNA expression level and Bax protein mRNA expression level were significantly increased, while Bcl-2 mRNA expression level was significantly decreased. While Caspase-3 mRNA expression level and Bax protein mRNA expression level decreased with morin treatment, Bcl-2 mRNA expression level increased significantly. Molecular docking study results showed good binding affinity of morin in SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-alpha, and IL-1 beta structures. Morin showed antioxidant, anti-inflammatory, and anti-apoptotic effects against Arsenic-induced cellular toxicity. Graphical Abstract