Person: ERTAŞ, BÜŞRA
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ERTAŞ
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BÜŞRA
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Publication Open Access A novel multi-target strategy for Alzheimer?s disease treatment via sublingual route: Donepezil/memantine/curcumin-loaded nanofibers(2022-07-01) BÖCEKÇİ, VEYSEL GÖKHAN; GÜNDÜZ, OĞUZHAN; ERTAŞ, BÜŞRA; Topal F., ERTAŞ B., Guler E., Gurbuz F., Ozcan G. S., Aydemir O., BÖCEKÇİ V. G., DURUKSU G., ŞAHİN ÇAM C., YAZIR Y., et al.Drug delivery systems that not only show efficacy through multiple therapeutic pathways but also facilitate patient drug use and exhibit a high bioavailability profile represent a promising strategy in the treatment of Alzheimer???s disease (AD). Here, donepezil (DO)/memantine (MM)/curcumin (CUR)-loaded electrospun nanofibers (NFs) were produced for the treatment of AD. DSC, XRD, and FT-IR studies demonstrated the complete incorporation of the drug into PVA/PVP NFs. The disintegration profile was improved by loading the drugs in PVA/PVP with fast wetting (less than 1 s), the start of disintegration (21 s), and dispersion in 110 s. The desired properties for sublingual application were achieved with the dissolution of NFs in 240 s. The cell viability in DO/ MM/CUR-loaded NFs was similar to the control group after 48 h in the cell culture. DO/MM/CUR-loaded NFs enhanced the expressions of BDNF (13.5-fold), TUBB3 (8.9-fold), Neurog2 (5.6-fold), NeuroD1 (5.8-fold), Nestin (166-fold), and GFAP (115-fold). DO/MM/CUR-loaded NFs and powder of these drugs contained in these fibers were daily administered sublingually to intracerebroventricular-streptozotocin (icv-STZ) treated rats. DO/MM/ CUR-loaded NFs treatment improved the short-term memory damage and enhanced memory, learning ability, and spatial exploration talent. Results indicated that the levels of A??, Tau protein, APP, GSK-3??, AChE, and TNF-?? were significantly decreased, and BDNF was increased by DO/MM/CUR-loaded NFs treatment compared to the AD group. In the histopathological analysis of the hippocampus and cortex, neuritic plaques and neurofibrillary nodes were not observed in the rats treated with DO/MM/CUR-loaded NFs. Taken together, the sublingual route delivery of DO/MM/CUR-loaded NFs supports potential clinical applications for AD.Publication Open Access Dose-dependent effect of Scolymus hispanicus L. (sevketibostan) on ethylene glycol-induced kidney stone disease in rats(2022-01-01) COŞKUN, ALİ; ERTAŞ, BÜŞRA; ELÇİOĞLU, HURİYE NURSEL; Coskun N. K., Coskun A., ERTAŞ B., Ahmad S., Ozdl M. U., ÇANKAYA S., ÇETİNKOL Y., Ozel Y., ELÇİOĞLU H. N.Kidney stone, also known as calcium oxalate nephrolithiasis, is one of the most common diseases worldwide. Calculi usually forms when urine becomes supersaturated with particular calcium salts such as calcium oxalate. In the present study, we investigated the ameliorative potential of the root extract of the Common golden thistle, Scolymus hispanicus L. (SH) on rats with ethylene glycol (EG) induced kidney stone disease. Sprague-Dawley rats, each weighing 250-300 g, were divided into three groups (n=6 per group): (i) Control (C); (ii) EG; and (iii) EG+SH. To induce nephrolithiasis, the rats received 1% of EG with drinking water, while the C group received normal drinking water during the study. SH extract 2 g/kg was added to the treatment from the 4th week onwards in EG+SH group. At the end of each experiment, rats were decapacitated and serum levels of calcium, magnesium, phosphorus, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were assessed in all groups at 0, 4, and 8 weeks. Oxalic acid and creatininelevels were measured in urine samples collected at 24 h in metabolic cages. Renal tissues were evaluated histopathologically at the end of the experiment. After 8 weeks, serum creatinine levels were found decreased in the SH group while increased in the EG group. Serum magnesium and AST levels were also found decreased in the EG group, however, SH treatment reversed these values. The SH treatment also increased urinary oxalic acid levels. When the kidney tissue of EG group was examined, there was a high level of crystal/stone, especially in the renal cortex. In kidney tissues of the SH group, only small amounts of crystal/stone were observed. Our experimental findings have demonstrated the ameliorative potential of the aqueous extracts of S. hispanicus roots and shells on EG-induced in the kidney stones in rats. Isolation of active compounds of SH would be desirable to understand the biochemical mechanism behind the process better.Publication Open Access Beta vulgaris L. var. cicla improves memory deficits in intracerebroventricular streptozotocin injected rats: Role on neuroinflammation(MARMARA UNIV, 2021) ERTAŞ, BÜŞRA; Ertas, Busra; Topal, Fadime; Gulhan, Rezzan; Yanardag, Refiye; Sacan, Ozlem; Sener, GokselAlzheimer's disease is a challenging disease for patients due to progressive loss of cognition and behavioral disorders. Disruption of cholinergic transmission and neuroinflammation are the most important mechanisms underlying cognitive damage. Beta vulgaris L. var. cicla (BV) has been reported to have various pharmacological effects associated with its rich antioxidant content. In addition, anti-cholinesterase and antiinflammatory activities of BV have been demonstrated in vitro. The aim of this study is to elucidate the therapeutic effect of BV against cognitive impairment, reduction in cholinergic transmission and neuroinflammation caused by intracerebroventricular (ICV) administration of streptozotocin (STZ). STZ was administered bilaterally at a dose of 3 mg/kg via ICV to rats, and BV treatment at a dose of 2 g/kg for 21 days was administered orally to STZ-induced animals. After behavioral tests, AChE activity, TNF-alpha and IL-1 beta levels were measured in hippocampus and cortex tissues excised from decapitated animals. Novel object recognition and passive avoidance test showed that the treatment of BV reverted the ICV-STZ induced memory dysfunctions in rats. Furthermore, increased AChE levels in the hippocampal and cortical tissues of STZ-induced rats were significantly reduced with 21 days of BV treatment. In conclusion, these results confirm that STZ administration caused cholinergic hypofunction, neuronal inflammation and cognitive dysfunction in rats, and BV therapy significantly inhibited these changes with its potential neuroprotective activity.Publication Open Access Investigation of the protective and therapeutic efficacy of Myrtus communis extract in aluminum chloride and Dgalactose- induced Alzheimer's disease in rats(2022-01-01) ŞEN, ALİ; ERTAŞ, BÜŞRA; YALMAN K., ŞEN A., ÇEVİK Ö., KADIOĞLU YAMAN S. B. , ERTAŞ B., Yıldız S., ŞENER G.This study investigated the possible protective and therapeutic effects of Myrtus communis subsp. communis ethanol extract (MC) in aluminum chloride (AlCl3) and D-galactose (D-Gal) induced Alzheimer's disease in rats. MC was orally given to rats as a protective treatment for 90 days and, in other two groups starting from the 60th day MC (100-200 mg/kg) was administered, concomitantly with AlCl3 and D-Gal. Learning and memory functions were evaluated by the behavioral tests. Biological activities of MC treatment were examined in hippocampal tissues by ELISA tests. D-Gal and AlCl3-treated rats showed increased amyloid beta (Aβ) and 8-hydroxy-2-deoxyguanosine (8- OHdG) levels, acetylcholinesterase activity and decreased neprilysin, Na+-K+ATPase and SOD levels in parallel with a decrease in Novel Object Recognition Test, Morris Water Maze and Passive Avoidance Test scores. On the other hand, MC administration reversed the behavioral impairments and improved learning and memory. Moreover, MC treatment decreased Aβ and 8-OHdG levels and acetylcholinesterase activity and increased neprilysin levels, Na+-K+ATPase and SOD levels. Our results suggest that MC has beneficial effects on cognitive and neuronal functions through its anticholinesterase and antioxidant properties.Publication Open Access Myrtus communis L. Extract Ameliorates High Fat Diet Induced Kidney and Bladder Damage by Inhibiting Oxidative Stress and Inflammation(2022-12-02) ERTAŞ, BÜŞRA; ŞEN, ALİ; AKAKIN, DİLEK; ERCAN, FERİHA; Kanpalta Mustafaoğlu F., Ertaş B., Şen A., Akakın D., Şener G., Ercan F.Objective: Obesity is associated with many diseases, including urinary system disorders such as chronic kidney disease and overactive bladder syndrome. Myrtus communis L. (MC) extract has been reported to have antioxidant and anti-inflammatory effects. The aim of this study was to investigate the protective effects of MC extract on high-fat diet (HFD)-induced kidney and bladder damage. Materials and Methods: Wistar albino male rats were divided into three experimental groups: control, HFD and HFD+MC. Experimental groups were fed a standard diet (control group) or HFD (HFD and HFD+MC groups) for 16 weeks. MC extract (100 mg/kg) was administered to the HFD+MC group orally during the last 4 weeks (5 days/week) of the experiment. Highdensity lipoprotein, total cholesterol, triglyceride and leptin levels were measured in blood serum. Tissue malondialdehyde (MDA), glutathione (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and myeloperoxidase (MPO) levels were evaluated biochemically. Kidney and bladder morphology, NADPH oxidase-2 (NOX-2) and nuclear factor-kappa B (NF-ҡB)-positive and apoptotic cells were evaluated histologically. Results: Lipid profiles altered and leptin levels increased in blood serum. MDA, 8-OHdG and MPO levels increased and GSH level decreased in kidney and bladder in the HFD group. Moreover, degenerated kidney and bladder morphology, increased NOX-2 and NF-ҡB-positive and apoptotic cells were observed in this group. All of these biochemical and histological parameters were ameliorated in the HFD+MC group. Conclusion: HFD-induced obesity causes kidney and bladder damage by oxidative and inflammatory processes. MC extract may reduce oxidative stress and inflammation and play a protective role in obesity-related kidney and bladder damage.Publication Open Access Protective effects of Rubus tereticaulis leaves ethanol extract on rats with ulcerative colitis and bio-guided isolation of its active compounds: A combined in silico, in vitro and in vivo study(2022-11-01) ŞEN, ALİ; ÖZBEYLİ, DİLEK; ERTAŞ, BÜŞRA; DOĞAN, AHMET; BİTİŞ, LEYLA; Şen A., Özbeyli D., Teralı K., Göger F., Yıldırım A., Ertaş B., Doğan A., Bitiş L., Şener G.The aim of this study was to evaluate the therapeutic effect of active ethanol extract obtained from the leaves of Rubus tereticaulis (RTME) against colitis, and to purify major compounds from this extract by bioassay-directed isolation. Rats with colitis induced via intra-rectal acetic acid administration (5%, v/v) received RTME or sulfasalazine for three consecutive days. On day four, all rats were decapitated, and the colonic tissue samples were collected for macroscopic score, colon weight, reduced glutathione (GSH), myeloperoxidase (MPO), and malondialdehyde (MDA) analyses. The active compounds and chemical composition of RTME were determined by bio-guided isolation and LC-MS/MS, respectively. Compared to the colitis group, the rats treated with RTME displayed significantly lowered macroscopic scores and colon wet weights (p < 0.001). These effects were confirmed biochemically by a decrease in colonic MPO activity (p < 0.001), MDA levels (p < 0.001), and an increase in GSH levels (p < 0.001). Kaempferol-3-O-β-d-glucuronide (RT1) and quercetin-3-O-β-d-glucuronide (RT2) were found to be the major compounds of RTME, as evidenced by in vitro anti-inflammatory and antioxidant activity-guided isolation. Their anti-inflammatory/antioxidant activities were also predicted by docking simulations. Additionally, quinic acid, 5-caffeoylquinic acid, quercetin pentoside, quercetin glucoside, quercetin-3-O-β-d-glucuronide, kaempferol-3-O-β-d-glucuronide, and kaempferol rutinoside were identified in RTME via using LC-MS/MS. RT2, along with other compounds, may be responsible for the observed protective action of RTME against colitis. This study represents the first report on the beneficial effects of RTME in an experimental model of colitis and highlights the potential future use of RTME as a natural alternative to alleviate colitis.Publication Open Access Antidiabetic effects of Salvia triloba and Thymus praecox subsp. skorpilii var. skorpilii in a rat model of streptozotocin/nicotinamide-induced diabetes(MARMARA UNIV, FAC PHARMACY, 2017-10-03) ERTAŞ, BÜŞRA; Cam, Muhammet Emin; Yildiz, Sila; Ertas, Busra; Acar, Ayse Eda; Taskin, Turgut; Kabasakal, LeventSome Salvia and Thymus species of Lamiaceae family come into prominence with strong antidiabetic effects. Compared to the other species, there are limited studies on antidiabetic activity of Salvia triloba (ST) and Thymus praecox subsp. skorpilii var. skorpilii (TPS). The aim of this study was to adjust the dosage and to determine the antidiabetic effects of methanol extracts of ST and TPS in streptozotocin/nicotinamide-induced diabetic rats. Type II diabetes mellitus (T2DM) was induced by a single intraperitoneal (i. p.) injection of streptozotocin (STZ) dissolved in 0.1 M cold citrate buffer (pH 4.5) at a dose of 55 mg/kg/body weight (b.w.) and nicotinamide (100 mg/kg/b.w.) was given prior to STZ injection. For adjusting dosage, oral glucose tolerance test (OGTT) was used while insulin tolerance test (ITT), OGTT, blood glucose levels and animal weights were used to evaluate the antidiabetic effects of ST and TPS. According to the OGTT, the most effective doses for ST and TPS were 200 mg/kg and 100 mg/kg, respectively. At the end of three weeks, blood glucose levels of control goup reached to 462.50 mg/dl, whereas ST and TPS-treated groups blood glucose levels decreased less than 200.00 mg/dl. In conclusion, the present study suggests that both of ST and TPS methanolic extracts may be of therapeutic benefit in diabetes and thus need to further studies.Publication Open Access Apocynin ameliorates testicular toxicity in high-fat diet-fed rats by regulating oxidative stress(2023-03-01) ERTAŞ, BÜŞRA; ERCAN, FERİHA; Hersek İ., Coşkunlu B., Köroğlu M., Ertaş B., Şener G., Ercan F.Objective: The purpose of this study was to examine the effects of apocynin (APC), an inhibitor of NADPH oxidase (NOX), on high-fat diet (HF)-induced testis cytotoxicity.Methods: Wistar albino rats were divided into three groups as control, HF and HF+APC groups. Rats in HF and HF+APC groups were fed using HFfor 16 weeks and in the last four weeks of this period vehicle solution or APC (25 mg/kg) was administered orally five days a week, respectively.Control group was fed with standart lab chow for 16 weeks. Cholesterol, triglyceride, high-density lipoproteins, leptin, estrogen, testosterone,LH and FSH were estimated in blood serum. Sperm parameters were analysed from the epididymis. Testicular malondialdehyde, 8‐hydroxy‐2‐deoxyguanosine, glutathione, superoxide dismutase and myeloperoxidase levels were estimated biochemically. Testicular morphology,proliferative, apoptotic and NOX2-positive cells were analysed histologically.Results: HF-induced obesity caused significant alterations in serum lipid and hormone profiles. Testicular malondialdehyde, 8‐hydroxy‐2‐deoxyguanosine, and myeloperoxidase levels increased, glutathione and superoxide dismutase levels decreased in this group. Moreover,altered sperm parameters, increased degenerated seminiferous tubules, apoptotic and NOX2 – positive cells and decreased proliferative cellswere observed in the HF group. All these biochemical and histological alterations improved in the HF+APC group.Conclusion: HF-induced obesity causes altreations in lipid values, sperm parameters and testicular morphology by increasing oxidative stressthrough NOX2 activity. Apocynin might prevent testis damage via regulating oxidant/antioxidant balance.Publication Open Access The effects of Urtica dioica L. ethanolic extract against urinary calculi in rats(MARMARA UNIV, 2020-03-12) DOĞAN, AHMET; Keles, Rumeysa; Sen, Ali; Ertas, Busra; Kayali, Damla; Eker, Pinar; Sener, Tarik Emre; Dogan, Ahmet; Cetinel, Sule; Sener, GokselNephrolithiasis is common urological problem and stone formation has multiple underlying pathogenetic factors. We investigated the possible preventive and therapeutic effect of Urtica dioica ethanol extract (UD) on ethylene glycol-induced nephrolithiasis model in rats. Sprague-Daw ley rats were divided into lour groups (n = 10). The control group was given normal drinking water for 8 weeks and was administered vehicle by gastric gavage. Stone formation was induced by adding 0.75% ethylene glycol (EG) to their drinking water. UD (700 mg/kg) was given orally lor 8 weeks to the preventive group and I or last 4 weeks to the treatment respectively. At the end of the experiment, urine, blood samples and kidney tissues were obtained. In 24-hour urine samples, calcium and citrate levels were decreased and oxalate levels were increased in EG whereas LID treatment groups reversed these parameters back to control levels. In addition, serum levels of creatinine and urea were increased in EG while LID significantly reduced these parameters. Malondialdehyde, 8-hydroxydeoxyguanosine and tumor necrosis alpha levels, and caspase- 3 and N-acetyl-beta-glucosaminidase activities were elevated in EG group and showed a decrease in LID treated groups. Glutathione level was decreased in EG group, whereas it was increased in UD preventive group. Histological examination showed an improvement in UD treated groups. Our results suggest that UD is effective both in prevention and treatment for kidney stones. The mechanism underlying this effect may be the antioxidant effect of UD and the effect on the concentration of stone-forming components in the urine.Publication Open Access The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression(MARMARA UNIV, 2019-05-15) ERTAŞ, BÜŞRA; Ayaz Adakul, Betul; Ertas, Busra; Cevikelli, Zatiye Ayca; Ozbeyli, Dilek; Ercan, Feriha; Kandemir, Cansu; Cevik, Ozge; Sener, Tarik Emre; Sener, GokselReactive oxygen metabolites play important roles in ischemia/reperfusion (I/R) injury in several organ systems. Riboflavin has been shown to exert antioxidant and/or anti-inflammatory activities in several experimental models. The aim of this study was to investigate the role of riboflavin against I/R injury in the rat kidney. Wistar albino rats 200-300 g weighing were divided into 3 groups. One week after unilateral nephrectomy, the IR procedure was applied to the rats. To induce I/R injury renal pedicle was clamped for 45 minutes and then rats were allowed reperfusion for 6 hours. Riboflavin (25 mg/ kg, orally) or vehicle was administered for one week as pretreatment. After decapitation, kidney tissue samples were taken for the evaluation of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and 8-hydroxydeoxyguanosine (8-OHdG), a specific marker of oxidative DNA damage. Furthermore, myeloperoxidase (MPO) and caspase-3 activities were also examined together with histological analysis. Ischemia/reperfusion induced significant increases in MDA and 8-OHdG levels and MPO and caspase- 3 activities, and decrese in GSH levels. In the riboflavin treatment these indices were found to be reversed back to control levels. The present data demonstrated that riboflavin, through its antioxidant effect, attenuates I/R induced acute renal injury in rats.