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 Metadata only Mesenchymal stem cell therapy improves erectile dysfunction in experimental spinal cord injury(SPRINGERNATURE, 2020) ERTAŞ, BÜŞRA; Albayrak, Omercan; Sener, Tarik Emre; Ersahin, Mehmet; Ozbas-Turan, Suna; Ekentok, Ceyda; Tavukcu, Hasan Huseyin; Cevik, Ozge; Cetinel, Sule; Ertas, Blisra; Sener, GokselThe aim of this study is to investigate the therapeutic potential of adipose-derived mesenchymal stem cell (AD-MSC) from brown adipose tissue on erectile dysfunction (ED) in experimentally induced spinal cord injury in rats. 24 male Wistar rats were divided into 3 groups; control, spinal cord injury (SCI) + vehicle, and SCI + AD-MSC. To induce SCI, a standard weight-drop method that induced a moderate to severe injury (100 g/cm force) at T7-T10, was used. AD-MSC (3 x 105 cells /5 mu L) was applied by local transplantation into the region of injury. At the end of four-weeks, rats underwent neurological examinations and then intracavernosal and mean arterial pressures (ICP and MAP) measurements. After decapitation, spinal cord and cavernosal tissue samples were taken to analyze neuronal nitric oxide synthase (n-NOS), proto-oncogene protein c-FOS and nerve growth factor (NGF). Tissues were also examined histologically. Spinal cord injury caused decrease on NGF and n-NOS levels while c-FOS was increased. The ICP/MAP value in vehicle-treated SCI rats was found to be significantly higher than the control group. On the other hand, in SCI + AD-MSC group, all these parameters were reversed back to control levels. AD-MSC therapy may be beneficial against erectile dysfunction in experimentally induced SCI by ameliorating neuronal damage.Publication Metadata only MYRTUS COMMUNIS IMPROVES COGNITIVE IMPAIRMENT IN RENOVASCULAR HYPERTENSIVE RATS(POLISH PHYSIOLOGICAL SOC, 2020) ŞEN, ALİ; Cevikelli-Yakut, Z. -A.; Ertas, B.; Sen, A.; Koyuncuoglu, T.; Yegen, B. C.; Sener, G.Myrtus communis has anti-inflammatory, neuroprotective and anticholinesterase activities yet there have been limited studies examining effects of Myrtus communis on cognitive functions. This study investigated the possible effects of Myrtus communis on changes in the cognitive functions of experimental renovascular hypertensive rats. Fifty-six Wistar-Albino rats were equally divided into 4 groups; sham-operated control, renovascular hypertension (RVH), ramipril (RVH + Ram) and Myrtus communis extract (RVH + MC) treatment groups. Goldblatt's 2-kidney 1-clip (2K1C) method was used to induce RVH. At the end of 9 weeks of treatment, after blood pressure recording, the animals underwent new object recognition test and Morris water maze (MWM) task. Following these tests, blood brain barrier (BBB) integrity was examined in 6 animals from each group. In the others after decapitation, osteopontin and interleukin (IL)-10 levels were measured in blood samples; while matrix metalloproteinase (MMP)-13, sodium potassium adenosine triphosphatase (Na+,K+-ATPase), cluster of differentiation (CD) 36, amyloid beta (Ab), neprilysin levels, and acetylcholinesterase (AChE) activity were investigated in hippocampal tissues. In RVH group, high systolic blood pressure decreased serum IL-10 levels, increased serum osteopontin levels and also impaired BBB permeability. Hippocampal MMP-13, CD36, Ab, neprilysin levels and AChE activities were elevated, while there were decreases in Na+,K+-ATPase levels. In new objet recognition test, discrimination index (DI) was determined as lower in saline-treated RVH group compared to control animals. In MWM training trail, 4th day performance in finding platform was significantly reduced in saline-treated RVH group compared to control group. RVH also decreased the time spent in target quadrant in probe test of MWM task compared to control group. In both of the treatment groups, all biochemical parameters were restored in parallel with improvement in the behavioral test performances. The results of this study suggest that Myrtus communis extract may improve the cognitive dysfunctions in hypertension through antihypertensive, anti-inflammatory and anticholinesterase activities.Publication Metadata only Myrtus communis leaf extract protects against cerulein-induced acute pancreatitis in rats(WILEY, 2020) ŞEN, ALİ; Ozbeyli, Dilek; Sen, Ali; Kaya, Ozlem Tugce Cilingir; Ertas, Busra; Aydemir, Sezgin; Ozkan, Naziye; Yuksel, Meral; Sener, GokselIn this study, the aim was to examine the potential protective effects of Myrtus communis subsp. communis leaf ethanol extract (MC) treatment against acute pancreatitis (AP) in rats. Thirty-two rats were grouped as the saline-pretreated control (C), MC-pretreated control (MC), saline-pretreated AP (AP), and MC-pretreated AP (MC + AP) groups. To induce AP, cerulein was administered (50 mu g/kg) two times. The rats were given MC for 14 days before cerulein injection. Six hours after the final cerulein injection, the rats were sacrificed. Pancreatic damage was associated with an increase in the serum activity of lipase and amylase, the pancreatic activity of myeloperoxidase, and the pancreatic level of malondialdehyde, interleukin-1 beta, and interleukin-6. AP also led to a decrease in the pancreatic level of anti-inflammatory interleukin-10 and glutathione. Pretreatment with MC before the induction of AP significantly reduced the pancreatic damage observed during the histological examination as well as reversed the biochemical changes evoked by AP. Practical applications Acute pancreatitis is characterized by high mortality (average about 5%; severe cases may reach about 30%). The current treatment for acute pancreatitis is mainly symptomatic. The introduction of herbal drugs may lead to the development of a new strategy in the treatment of this disease. This study revealed that MC reduced pancreatic injury by decreasing pro-inflammatory cytokines, increasing antioxidant capacity and anti-inflammatory cytokine, IL-10. To the authors' knowledge, this research is the first report showing that MC inhibits the development of AP. This observation suggests that MC may be useful in the prevention and the treatment of AP in clinical settings.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 Metadata only Myrtus communis subsp. communis improved cognitive functions in ovariectomized diabetic rats(ELSEVIER, 2020) ŞEN, ALİ; Yaman, Beril Kadioglu; Cevik, Ozge; Yalman, Kubra; Ertas, Busra; Sen, Ali; Sener, GokselAim: The purpose of this study was to investigate the possible effects of Myrtus communis subsp. communis (MC) on cognitive impairment in ovariectomized diabetic rats. Material and method: Female Sprague-Dawley rats were divided into 5 groups consisting of 15 rats each; Control (C), Diabetes (D), Ovariectomy and diabetes (OVX + D), Ovariectomy, diabetes and donepezil (OVX + D + Don), Ovariectomy, diabetes and Myrtus communis subsp. communis (OVX + D + MC). Blood glucose measurements were made at the beginning and end of the experiments. The animals underwent the novel object recognition test (NORT) and their performance was evaluated. In hippocampal tissues; amyloid beta (A beta) and neprilysin levels, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities, polysialylated neural cell adhesion molecule (PSA-NCAM), alpha 7 subunit of neuronal nicotinic acetylcholine receptor (alpha 7-nAChR) and brain derived neurotrophic factor (BDNF) gene expressions were examined. Results: Animals with ovariectomy and diabetes showed increased levels of blood glucose, AChE activity and A beta levels, and decreased neprilysin levels, ChAT activity, alpha 7-nAChR, PSA-NCAM and BDNF gene expressions in parallel with a decrease in NORT performance score. On the other hand, in the MC-treated OVX + D group, there was a significant decrease observed in blood glucose levels and AChE activities while there was improvement in NORT performances and an increase in hippocampal ChAT activity, neprilysin levels, alpha 7-nAChR, PSA-NCAM and BDNF expressions. Conclusion: These results suggest that MC extract could improve cognitive and neuronal functions with its anticholinesterase and antihyperglycemic properties.
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