ASSAF, N. A. G. L. A. A., M. E. El-Shamarka, N. A. Salem, and N. E. S. Sayed, "Neuroprotective effect of PPAR alpha and gamma agonists in a mouse model of amyloidogenesis through modulation of the Wnt/beta catenin pathway via targeting alpha- and beta-secretases", Progress in Neuropsychopharmacology and Biological Psychiatry, vol. 97, issue 109793, pp. 1-13, 2020. paper_1.pdf
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.

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.

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.

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
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
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