Neurotherapeutic effects of quercetin-loaded nanoparticles and Biochanin-A extracted from Trifolium alexandrinum on PI3K/Akt/GSK-3ß signaling in the cerebral cortex of male diabetic rats.

Diabetes mellitus (DM) is a severe metabolic disease that can have significant consequences for cognitive health. Bioflavonoids such as Trifolium alexandrinum (TA), quercetin (Q), and Biochanin-A (BCA) are known to exert a wide range of pharmacological functions including antihyperglycemic activity. This study aimed to investigate the neurotherapeutic effects of quercetin-loaded nanoparticles (Q-LNP) and BCA extracted from TA against diabetes-induced cerebral cortical damage through modulation of PI3K/Akt/GSK-3ß and AMPK signaling pathways. Adult male Wistar albino rats (N = 25) were randomly assigned to one of five groups: control, diabetics fed a high-fat diet (HFD) for 2 weeks and intraperitoneally (i.p.) injected with STZ (40 mg/kg), and diabetics treated with Q-LNP (50 mg/kg BW/day), BCA (10 mg/kg BW/day), or TA extract (200 mg/kg BW/day). Treatments were applied by oral gavage once daily for 35 days. Diabetic rats treated with Q-LNP, BCA, and TA extract showed improvement in cognitive performance, cortical oxidative metabolism, antioxidant parameters, and levels of glucose, insulin, triglyceride, and total cholesterol. In addition, these treatments improved neurochemical levels, including acetylcholine, dopamine, and serotonin levels as well acetylcholinesterase and monoamine oxidase activities. Furthermore, these treatments lowered proinflammatory cytokine production for TNF-α and NF-κB; downregulated the levels of IL-1ß, iNOS, APP, and PPAR-γ; and attenuated the expressions of PSEN2, BACE, IR, PI3K, FOXO 1, AKT, AMPK, GSK-3ß, and GFAP. The histopathological examinations of the cerebral cortical tissues confirmed the biochemical results. Overall, the present findings suggest the potential therapeutic effects of TA bioflavonoids in modulating diabetes-induced cerebral cortical damage.

Analysis of Melatonin-Modulating Effects Against Tartrazine-Induced Neurotoxicity in Male Rats: Biochemical, Pathological and Immunohistochemical Markers.

Tartrazine (E-102) is one of the most widely used artificial food azo-colors that can be metabolized to highly sensitizing aromatic amines such as sulphanilic acid. These metabolites are oxidized to N-hydroxy derivatives that cause neurotoxicity. Melatonin is a neurohormone. That possesses a free-radical scavenging effect. The present work was mainly designed to evaluate the possible ameliorative role of melatonin against tartrazine induced neurotoxicity in cerebral cortex and cerebellum of male rats. Adult male rats were administered orally with tartrazine (7.5 mg/kg) with or without melatonin (10 mg/kg) daily for four weeks. The data revealed that tartrazine induced redox disruptions as measured by significant (p < 0.05) increased malondialdehyde (MDA) level and inhibition of (GSH) concentration and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzyme activities. Besides, brain acetyl cholin (Ach) and gamma-aminobutyric acid (GABA) were elevated while, dopamine (DA) was depleted in trtrazine -treated rats. Moreover, tartrazine caused a significant (p < 0.05) increase in the brain interleukin-6 (IL-6), interleukin-1ß (IL-1 ß) and tumor necrosis factor-α (TNFα). At the tissue level, tartrazine caused severe histopathological changes in the cerebellum and cerebral cortex of rats. The immunohistochemical results elucidated strong positive expression for Caspase-3 and GFAP and weak immune reaction for BcL2 and synaptophysin in tatrazine- treated rats. The administration of melatonin to tartrazine -administered rats remarkably alleviated all the aforementioned tartrzine-induced effects. It could be concluded that, melatonin has a potent ameliorative effect against tartrazine induced neurotoxicity via the attenuation of oxidative/antioxidative responses.

Therapeutic effects of astragaloside IV and Astragalus spinosus saponins against bisphenol A-induced neurotoxicity and DNA damage in rats.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor to which humans are often subjected during daily life. This study aimed to investigate the ameliorative effect of astragaloside IV (ASIV) or saponins extracted from Astragalus spinosus (A. spinosus) against DNA damage and neurotoxic effects induced by BPA in prefrontal cortex (PFC), hippocampal and striatal brain regions of developing male rats. MATERIALS AND METHODS: Juvenile PND20 (pre-weaning; age of 20 days) male Sprague Dawley rats were randomly and equally divided into four groups: control, BPA, BPA+ASIV and BPA+A. spinosus saponins groups. Bisphenol A (125 mg/kg/day) was administrated orally to male rats from day 20 (BPA group) and along with ASIV (80 mg/kg/day) (BPA+ASIV group) or A. spinosus saponin (100 mg/kg/day) (BPA+ A. spinosus saponins group) from day 50 to adult age day 117. RESULTS: Increased level of nitric oxide (NO) and decreased level of glutamate (Glu), glutamine (Gln), glutaminase (GA) and glutamine synthetase (GS) were observed in the brain regions of BPA treated rats compared with the control. On the other hand, co-administration of ASIV or A. spinosus saponin with BPA considerably improved levels of these neurochemicals. The current study also revealed restoration of the level of brain derived neurotrophic factor (BDNF) and N-methyl-D-aspartate receptors (NR2A and NR2B) gene expression in BPA+ ASIV and BPA+A. spinosus saponins groups. The co-treatment of BPA group with ASIV or A. spinosus saponin significantly reduced the values of comet parameters as well as the intensity of estrogen receptors (ERs) immunoreactive cells and improved the histological alterations induced by BPA in different brain regions. CONCLUSION: It could be concluded that ASIV or A. spinosus saponins has a promising role in modulating the neurotoxicity and DNA damage elicited by BPA.

Soybean isoflavone ameliorates cognitive impairment, neuroinflammation, and amyloid ß accumulation in a rat model of Alzheimer's disease.

Oxidative stress and neuroinflammatory changes appear to be the early events involved in AD's development and progression. The present study was designed to assess the effect of soybean isoflavone extract (SIFE) against colchicine-induced cognitive dysfunction and oxidative stress in male rats.Fifty adult male Wistar albino rats were divided into five groups: control, ACSF-treated group, soybean isoflavones (SIF)-treated group, colchicine (COL)-treated group, and SIF + COL-treated group. We found that an intracerebroventricular (icv) injection of a single dose of colchicine (7.5 µg/rat bilaterally) resulted in learning deficits in rats subjected to the Morris water maze task associated with marked oxidative damage and decreased acetyl cholinesterase (AChE) activity. In addition, COL caused significant increase in amyloid beta peptide 1-42 (ß, amyloid 1-42) interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNFα), cyclooxygenase-2 (COX-2) and TNF-α genes expression in the brain, and glial fibrillary acidic protein (GFAP) in cortical astrocytes in the brain cortex.Treatment with SIFE (80 mg/kg b.wt) daily for 14 days followed by a single dose of COL significantly reduced the elevated oxidative stress parameters and restored the reduced antioxidant activities. Besides, the administration of SIFE reversed the overproduction of ß, amyloid 1-42, pro-inflammatory cytokines, and GFAP in the brain. The obtained results were confirmed by histological observations that clearly indicate a neuroprotective effect of SIF against AD.