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Thabit, S., H. Handoussa, M. Roxo, B. C. de Azevedo, N. S E El Sayed, and M. Wink, "(L.) Schott Fruits Increase Stress Resistance and Exert Antioxidant Properties in and Mouse Models.", Molecules (Basel, Switzerland), vol. 24, issue 14, 2019. Abstractpaper_iii.pdf

(L.) Schott is a popular Asian tree widely used in traditional medicine. The current study explored the potential stress resistance and antioxidant activities of its fruits. Phytochemical profiling of the hydroalcoholic fruit extract was done via high performance liquid chromatography-photodiode array-electrospray ionization-mass/mass (HPLC-PDA-ESI-MS/MS). Twenty four phenolic constituents were tentatively identified in the extract. The () nematode model in addition to trimethyltin (TMT)-induced neurotoxicity mouse model were used for in vivo evaluation of its antioxidant properties. The ability of the extract to enhance stress resistance was manifested through increasing survival rate by 44.7% and decreasing basal reactive oxygen species (ROS) levels by 72.3% in . In addition, the extract increased the levels of the stress response enzyme superoxide dismutase-3 (Sod-3) by 55.5% and decreased the expression of heat shock protein-16.2 (Hsp-16.2) in nematodes, which had been challenged by juglone, by 21%. Using a mouse model, the extract significantly decreased the expression of the oxidative stress marker malondialdehyde (MDA). Furthermore, an elevation in the levels of the antioxidant marker glutathione (GSH), SOD and heme oxygenase-1 (HO-1) enzymes were observed. Our findings imply that has the potential to be used in future studies focusing on diseases associated with oxidative stress.

Ekladious, S. T., and N. S. El Sayed, "Effect of pioglitazone and simvastatin in lipopolysaccharide-induced amyloidogenesis and cognitive impairment in mice: possible role of glutamatergic pathway and oxidative stress.", Behavioural pharmacology, vol. 30, issue 1, pp. 5-15, 2019. Abstract

Neuroinflammation and β-amyloid (Aβ) deposition in the brain are well known characteristics of neurodegeneration. Diabetes and hypercholesterolemia are the main risk factors leading to memory loss and cognitive impairment. Recently, it was found that statins and thiazolidinediones have promising anti-inflammatory and neuroprotective effects that could delay neurodegeneration and neuronal loss in diabetic and hypercholesterolemic patients. The aim of the present study was to investigate the protective effect of simvastatin, pioglitazone, and their combination in lipopolysaccharide (LPS)-induced neuroinflammation and amyloidogenesis. Mice were divided into five groups: group 1 received 0.9% saline, group 2 received LPS (0.8 mg/kg in saline), group 3 received LPS (0.8 mgl kg)+simvastatin (5 mg/kg in saline), group 4 received LPS (0.8 mg/kg)+pioglitazone (20 mg/kg in saline), group 5 receiving LPS (0.8 mg/kg)+simvastatin (5 mg/kg)+pioglitazone (20 mg/kg). Y-maze and novel object recognition were used to assess the spatial and nonspatial behavioral changes. Nitric oxide levels and glutamate levels were measured to elucidate the anti-glutamatergic and anti-inflammatory effects of the tested drugs. Immunohistochemistry was performed to detect the presence of Aβ1-42 in the mice brain. LPS impaired memory, and increased Aβ deposition, nitric oxide, and glutamate brain levels. Both drugs produced a significant improvement in all parameters. We conclude that simvastatin and pioglitazone may have a protective effect against cognitive impairment induced by LPS, through targeting the glutamatergic and inflammatory pathways, especially in patients having hypercholesterolemia and diabetes.

El Sayed, N. S., and A. S. Sayed, "Protective effect of methylene blue on TNBS-induced colitis in rats mediated through the modulation of inflammatory and apoptotic signalling pathways.", Archives of toxicology, vol. 93, issue 10, pp. 2927-2942, 2019. Abstract

Ulcerative colitis (UC) is a common type of chronic, idiopathic inflammatory bowel disease (IBD) that affects the mucosal lining of the colon. Long-term UC remission has shed light on the necessity of modified therapeutic strategies. In this study, UC was induced in rats by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The anticolitis effect of methylene blue (MB), a well-known dye and antioxidant and a potent mitochondrial enhancer was tested. MB was injected intraperitoneally (i.p.) at a dose of 1 mg/kg, 2 mg/kg or 4 mg/kg, and colosalazine was administered orally (p.o.) at a dose of 500 mg/kg 11 days after the administration of TNBS, which was injected on the 8th day. All treatment group results were compared to the TNBS group results. Macroscopically, limited body weight loss and decrease in the colon weight per unit length ratio were observed in the MB groups. MB improved histological damage and decreased the expression of myeloperoxidase (MPO) and accumulation of CD4 lymphocytes observed by immunohistochemistry. Downregulation of Bax/Bcl protein expression was detected using Western blotting, and increased mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was measured by qPCR. MB produced biochemical alterations, such as significant decrease in interleukin-6 (IL-6), interleukin-17 (IL-17) and intercellular adhesion molecule-1 (ICAM-1) levels measured by enzyme-linked immunosorbent assay (ELISA). Significant decrease in malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) levels as well as significant increase in superoxide dismutase (SOD) and mitochondrial cytochrome c oxidase levels were observed with MB, and these effects were similar to those produced by colosalazine. Thus, MB altered disease pathogenesis and could be a promising and challenging therapeutic target for UC treatment.

Thabit, S., H. Handoussa, M. Roxo, N. S. El Sayed, B. C. de Azevedo, and M. Wink, "Evaluation of antioxidant and neuroprotective activities of Cassia fistula (L.) using the Caenorhabditis elegans model", PeerJ, vol. 6, issue e5159, pp. 1-33, 2018. paper_3_sara.pdf
Mansour, R. M., M. A. E. Ahmed, A. E. El-Sahar, and N. S. El Sayed, "Montelukast attenuates rotenone-induced microglial activation/p38 MAPK expression in rats: Possible role of its antioxidant, anti-inflammatory and antiapoptotic effects", Toxicology and applied pharmacology, vol. 358 , pp. 76–85, 2018. paper_8_montelukast.pdf
A, F. I., N. M. Sharaf, R. M. El Abdelghany, and N. S. El Sayed, "Neuromodulatory Effect of Thymoquinone in Attenuating Glutamate-Mediated Neurotoxicity Targeting the Amyloidogenic and Apoptotic Pathways", Frontiers in Neurology, vol. 9, pp. 236, 2018. paper_1_ibram.pdf
Sayed, A. S., I. M. A. N. E. GOMAA, M. Bader, and N. S. El Sayed, "Role of 3-Acetyl-11-Keto-Beta-Boswellic Acid in Counteracting LPS-Induced Neuroinflammation via Modulation of miRNA-155", Molecular Neurobiology, vol. 55, pp. 5798–5808, 2018. paper_6_aya.pdf
Abbas, H., H. Refai, and N. S. El Sayed, "Superparamagnetic Iron OxideeLoaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam", Journal of Pharmaceutical Sciences, vol. 107, pp. 2119-2127, 2018. paper_5_haidy.pdf
Abdel Rasheed, N. O., N. S. El Sayed, and A. S. El-Khatib, "Targeting central β2 receptors ameliorates streptozotocin-induced neuroinflammation via inhibition of glycogen synthase kinase3 pathway in mice", Progress in Neuropsychopharmacology & Biological Psychiatry, vol. 86, pp. 65-75, 2018. paper_4_noura.pdf
Sayed, N. E. S., "Modulation of Estradiol and Neprilysin Pathways by Resveratrol in a Lipoplysaccharide Model of Cognitive impairment", Neuroprotective Effects of Phytochemicals in Neurological Disorders, New Jersey, John Wiley &Sons, 2017. ch19.pdf
Sorial, M. E., and N. E. S. Sayed, "Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer’s disease mouse model: possible involvement of the cholinergic system", Naunyn Schmiedebergs Archives of Pharmacology, 2017, vol. 390, pp. 581-593, 2017. paper_6.pdf
Waleed A.I. Khallaf, B. A. S. Messiha, A. M. H. Abo-Youssef, and N. S. El-Sayed, "Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor", Canadian journal of physiology and pharmacology, vol. 95, pp. 850-860, 2017. cjpp-2017-0042_1.pdf
Sayed, N. E. S., and Y. Bayan, "Possible role of resveratrol targeting estradiol and neprilysin pathways in lipopolysaccharide model of Alzheimer disease.", Advances in experimental medicine and biology, vol. 822, issue doi: 10.1007/978-3-319-08927-0_12., pp. 107-118, 2015.
Sayed, N. E. S., Y. Hassaan, H. Handoussa, and A. H. El-Khatib, "Evaluation of Plant Phenolic Metabolites as a Source of", BioMed Research International, vol. 2014, issue 2014, pp. 1-10, 2014.
Maher, A., N. S.El-Sayed, H. - G. Breitingera, and M. Z. Gad, "Overexpression of NMDAR2B in an inflammatory model of Alzheimer’s disease: Modulation by NOS inhibitors", Brain Research Bulletin, vol. 109 , issue 2014, pp. 109–116, 2014. paper_2.pdf
El-Halawany, A. M., R. S. E. Dine, N. E. S. Sayed, and M. Hattori, "Protective Effect of Aframomum melegueta phenolics Against CCl4-Induced Rat Hepatocytes Damage Role of Apoptosis and Pro-inflammatory Cytokines inhibition", Scientific reports, vol. 4 : 5880, issue 2014, pp. 1-9, 2014. paper_3.pdf