rutin and Memory-Disorders

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome. Paracetamol (APAP) causes, in high doses, a hepatic injury. Alogliptin (ALO), with its 100% oral bioavailability, may be able to reverse the acute hepatic injury and memory impairments.. Forty rats were divided into four groups as follows; Normal Control Group, APAP intoxicated group, ALO and SIL groups. Behavioral tests (Morris water maze, Y-maze spontaneous alteration, and novel object recognition test) were performed together with evaluating HE score. Neurotransmitters (gamma-aminobutyric acid, glutamate, dopamine, serotonin, norepinephrine and acetylcholine), as well as acetylcholinesterase activity, were determined in the hippocampus. Also, hepatotoxicity markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and ammonia) were measured in blood. Additionally, transforming growth factor beta 1, tumor necrosis factor alpha, cytochrome c, granzyme B and caspase-3, coiled-coil Moesin-like BCL-interacting protein 1 "beclin-1", cellular FLICE-like inhibitory protein, protein 53, TNF-α related apoptosis-inducing ligand, Fas-ligand and alpha-smooth muscle actin were measured in liver homogenate. Moreover, the histopathological investigation was performed.. APAP was able to disturb neurotransmitters which were mirrored in the performance of rats in the behavioral test. Most hepatotoxicity, apoptosis and inflammation indicators were elevated after APAP administration, while beclin-1 (autophagy marker) was declined. The tested drugs, both, reversed most of the last mentioned parameters but ALO was more efficient in reducing TGF-β1, α-SMA, TNF-α and ALP as well as increasing % alteration.. ALO and SIL elicited anti-apoptotic, anti-inflammatory and autophagic effects on paracetamol-damaged liver cells and improved memory impairments of HE.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents; Apoptosis; Autophagy; Behavior, Animal; Biomarkers; Chemical and Drug Induced Liver Injury; Dipeptidyl-Peptidase IV Inhibitors; Hepatic Encephalopathy; Hydroxyethylrutoside; Male; Maze Learning; Memory; Memory Disorders; Piperidines; Rats; Rats, Wistar; Uracil

Alzheimer׳s disease (AD) is a neurodegenerative disorder with a progressive cognitive decline and memory loss. Multiple pathogenetic factors including aggregated β-amyloid (Aβ), neurofibrillary tangles (NFTs), cholinergic dysfunction and oxidative stress are involved in AD. Aβ, a major constituent of the senile plaques, is a potent neurotoxic peptide and has a pivotal role in cognitive deficit and reduced synaptic plasticity in AD. In the present study we examined the protective effect of troxerutin, as a multipotent bioflavonoid, on Aβ (1-42)-induced impairment of evoked field potential in hippocampal DG neurons. Male Wistar rats were divided into four groups including Aβ (42-1), Aβ (1-42), Aβ (1-42) plus troxerutin and Aβ (42-1) plus troxerutin groups. Aβ was injected intracerebroventricularly (i.c.v.) into right lateral ventricle and after two weeks the evoked field potential recorded from perforant path-DG synapses to assess paired pulse paradigm and long term potentiation (LTP). Administration of Aβ (1-42) drastically attenuated the LTP of DG neurons, while there was no significant difference in evoked field potentials between Aβ (1-42) plus troxerutin group with respect to Aβ (42-1) group. This study revealed that troxerutin improves the synaptic failure induced by Aβ peptide and can be introduced as a promising multi-potent pharmacological agent in prevention or treatment of AD in the future.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Dentate Gyrus; Electrophysiological Phenomena; Hydroxyethylrutoside; Long-Term Potentiation; Male; Maze Learning; Memory Disorders; Neuronal Plasticity; Neuroprotective Agents; Rats; Rats, Wistar; Synapses

The C/EBP β is a basic leucine zipper transcription factor that regulates a variety of biological processes, including metabolism, cell proliferation and differentiation, and immune response. Recent findings show that C/EBP β-induced inflammatory responses mediate kainic acid-triggered excitotoxic brain injury. In this article, we show that protein kinase C ζ enhances K-ras expression and subsequently activates the Raf/MEK/ERK1/2 pathway in the hippocampus of domoic acid (DA)-treated mice, which promotes C/EBP β expression and induces inflammatory responses. Elevated production of TNF-α impairs mitochondrial function and increases the levels of reactive oxygen species by IκB kinase β/NF-κB signaling. The aforementioned inflammation and oxidative stress lead to memory deficits in DA-treated mice. However, troxerutin inhibits cyclin-dependent kinase 1 expression, enhances type 1 protein phosphatase α dephosphorylation, and abolishes MEK/ERK1/2/C/EBP β activation, which subsequently reverses the memory impairment observed in the DA-treated mice. Thus, troxerutin is recommended as a potential candidate for the prevention and therapeutic treatment of cognitive deficits resulting from excitotoxic brain damage and other brain disorders.

Topics: Animals; Butadienes; CCAAT-Enhancer-Binding Protein-beta; CDC2 Protein Kinase; Gene Knockdown Techniques; Genes, ras; Hippocampus; Hydroxyethylrutoside; Inflammation; Inflammation Mediators; Kainic Acid; Male; Memory Disorders; Mice; Mitochondria; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NADPH Oxidases; Nitriles; Oxidative Stress; Phosphoprotein Phosphatases; Phosphorylation; Protein Kinase C; Reactive Oxygen Species; Signal Transduction