Resveratrol-Selenium Nanoparticles Alleviate Neuroinflammation and Neurotoxicity in a Rat Model of Alzheimer's Disease by Regulating Sirt1/miRNA-134/GSK3ß Expression.

Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitive functions, neuroinflammation, and impaired signaling pathways. Resveratrol (RSV) has neuroprotective properties, but with low bioavailability, and low solubility in vivo. Selenium (Se) is an essential micronutrient for brain function. Thus, this study aimed to evaluate the role of formulated RSV-Se nanoparticles (RSV-SeNPs) on neurochemical and histopathological approaches associated with the AD model in rats induced by Aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 60 days. RSV-SeNPs supplementation attenuates the impaired oxidative markers and mitochondrial dysfunction. The ameliorative effect of RSV-SeNPs on cholinergic deficits was associated with clearance of amyloid ß (Aß). Furthermore, activation of phosphatidylinositol 3 kinase (PI3K) deactivates glycogen synthase kinase 3 beta (GSK-3ß)-mediated tau hyperphosphorylation. Additionally, RSV-SeNPs downregulate signal transducer and activator of transcription (STAT3) expression as well as interleukin-1ß (IL-1ß) levels, therefore alleviating neuroinflammation in AD. Moreover, RSV-SeNPs upregulate the expression of Sirtuin-1 (SIRT1) and lower that of microRNA-134, consequently increasing neurite outgrowth. Eventually, the obtained results showed that nano-formulation of resveratrol with selenium maximized the therapeutic potential of RSV against Alzheimer's disease not only by their antioxidant but also by anti-inflammatory effect improving the neurocognitive function and modulating the signaling pathways.

Ameliorating role of rutin on oxidative stress induced by iron overload in hepatic tissue of rats.

Iron is an essential element that participates in several metabolic activities of cells; however, excess iron is a major cause of iron-induced oxidative stress and several human diseases. Natural flavonoids, as rutin, are well-known antioxidants and could be efficient protective agents. Therefore, the present study was undertaken to evaluate the protective influence of rutin supplementation to improve rat antioxidant systems against IOL-induced hepatic oxidative stress. Sixty male albino rats were randomly divided to three equal groups. The first group, the control, the second group, iron overload group, the third group was used as iron overload+rutin group. Rats received six doses of ferric hydroxide polymaltose (100 mg kg(-1) b.wt.) as one dose every two days, by intraperitoneal injections (IP) and administrated rutin (50 mg kg(-1) b.wt.) as one daily oral dose until the sacrificed day. Blood samples for serum separation and liver tissue specimens were collected three times, after three, four and five weeks from the onset of the experiment. Serum iron profiles total iron, Total Iron Binding Capacity (TIBC), Unsaturated Iron Binding Capacity (UIBC), transferrin (Tf) and Transferrin Saturation% (TS%)}, ferritin, albumin, total Protein, total cholesterol, triacylglycerols levels and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were determined. Moreover, total iron in the liver, L-malondialdehyde (L-MDA), glutathione (GSH), Nitric Oxide (NO) and Total Nucleic Acid (TNA) levels and glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities were also determined. The obtained results revealed that, iron overload (IOL) resulted in significant increase in serum iron, TIBC, Tf, TS% and ferritin levels and AST and ALT activities and also increased liver iron, L-MDA and NO levels. Meanwhile, it decreased serum UIBC, total cholesterol, triacylglycerols, albumin, total protein and liver GSH, TNA levels and Gpx, CAT and SOD activities when compared with the control group. Rutin administration to iron-overloaded rats resulted in significant decrease in serum total iron, TIBC, Tf, TS%, ferritin levels and AST and ALT activities and liver total iron, L-MDA and NO levels with significant increases in serum UIBC, albumin, total protein and total cholesterol levels and in liver GSH, CAT and SOD activities compared with the IOL group. This study provides in vivo evidence that rutin administration can improve the antioxidant defense systems against IOL-induced hepatic oxidative stress in rats. This protective effect in liver of iron-loaded rats may be due to both antioxidant and metal chelation activities.