Schisandrin B Ameliorates ICV-Infused Amyloid β Induced Oxidative Stress and Neuronal Dysfunction through Inhibiting RAGE/NF-κB/MAPK and Up-Regulating HSP/Beclin Expression

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, antiinflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. Methods: BBR-NPs were formulated using ionic gelation method and tripolyphosphate was chosen as a cross linker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty six Wistar male rats were randomly distributed into: three control groups, received saline, polyethylene glycol or chitosan- NPs respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates as well as neuroplasticity markers and histopathological examination were assessed. Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands toward AChE and Aβ42 formation and significantly down regulated Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. Conclusions: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake which need more investigation in future work.

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Lethal weapon: amyloid β-peptide, role in the oxidative stress and neurodegeneration of Alzheimer’s disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2004.02.002 ◽

2004 ◽

Vol 25 (5) ◽

pp. 581-587 ◽

Cited By ~ 13

Author(s):

Debomoy K Lahiri ◽

Nigel H Greig

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Amyloid Β Peptide

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Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

Antioxidants ◽

10.3390/antiox8120630 ◽

2019 ◽

Vol 8 (12) ◽

pp. 630 ◽

Cited By ~ 6

Author(s):

Donald G Matthews ◽

Maya Caruso ◽

Charles F Murchison ◽

Jennifer Y Zhu ◽

Kirsten M Wright ◽

...

Keyword(s):

Oxidative Stress ◽

Amyloid Β ◽

Water Extract ◽

Centella Asiatica ◽

Antioxidant Response ◽

Plaque Burden ◽

Heme Oxygenase 1 ◽

Synaptic Density ◽

Cognitive Benefits ◽

5Xfad Mice

Centella asiatica (CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer’s disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response in aged WT mice. Here, CAW was administered to AD model 5XFAD female and male mice and WT littermates (age: 7.6 +/ − 0.6 months), and object recall and contextual fear memory were tested after three weeks treatment. CAW’s impact on amyloid-β plaque burden, and markers of neuronal oxidative stress and synaptic density, was assessed after five weeks treatment. CAW antioxidant activity was evaluated via nuclear transcription factor (erythroid-derived 2)-like 2 (NRF2) and NRF2-regulated antioxidant response element gene expression. Memory improvement in both genders and genotypes was associated with dose-dependent CAW treatment without affecting plaque burden, and marginally increased synaptic density markers in the hippocampus and prefrontal cortex. CAW treatment increased Nrf2 in hippocampus and other NRF2 targets (heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase catalytic subunit). Reduced plaque-associated SOD1, an indicator of oxidative stress, was observed in the hippocampi and cortices of CAW-treated 5XFAD mice. We postulate that CAW treatment leads to reduced oxidative stress, contributing to improved neuronal health and cognition.

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In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2009.10.035 ◽

2010 ◽

Vol 48 (1) ◽

pp. 136-144 ◽

Cited By ~ 122

Author(s):

D. Allan Butterfield ◽

Veronica Galvan ◽

Miranda Bader Lange ◽

Huidong Tang ◽

Renã A. Sowell ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer Disease ◽

Transgenic Mice ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Methionine 35

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Multiple signaling events in amyloid β-induced, oxidative stress-dependent neuronal apoptosis

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(03)00244-2 ◽

2003 ◽

Vol 35 (1) ◽

pp. 45-58 ◽

Cited By ~ 75

Author(s):

E Tamagno

Keyword(s):

Oxidative Stress ◽

Neuronal Apoptosis ◽

Amyloid Β ◽

Signaling Events ◽

Stress Dependent ◽

Multiple Signaling

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Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish

International Journal of Molecular Sciences ◽

10.3390/ijms19103195 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3195 ◽

Cited By ~ 17

Author(s):

Sreeja Sarasamma ◽

Gilbert Audira ◽

Stevhen Juniardi ◽

Bonifasius Sampurna ◽

Sung-Tzu Liang ◽

...

Keyword(s):

Oxidative Stress ◽

Zinc Chloride ◽

Short Term Memory ◽

Amyloid Β ◽

Antioxidant Defense System ◽

Significant Inhibition ◽

Control Group ◽

Adult Zebrafish ◽

Zebrafish Model ◽

Low Concentrations

In this study, we evaluated the acute (24, 48, 72, and 96 h) and chronic (21 days) adverse effects induced by low doses (0.1, 0.5, 1, and 1.5 mg/L) of zinc chloride (ZnCl2) exposure in adult zebrafish by using behavioral endpoints like three-dimensional (3D) locomotion, passive avoidance, aggression, circadian rhythm, and predator avoidance tests. Also, brain tissues were dissected and subjected to analysis of multiple parameters related to oxidative stress, antioxidant responses, superoxide dismutase (SOD), neurotoxicity, and neurotransmitters. The results showed that ZnCl2-exposed fishes displayed decreased locomotor behavior and impaired short-term memory, which caused an Alzheimer’s Disease (AD)-like syndrome. In addition, low concentrations of ZnCl2 induced amyloid beta (amyloid β) and phosphorylated Tau (p-Tau) protein levels in brains. In addition, significant induction in oxidative stress indices (reactive oxygen species (ROS) and malondialdehyde (MDA)), reduction in antioxidant defense system (glutathione (GSH), GSH peroxidase (GSH-Px) and SOD) and changes in neurotransmitters were observed at low concentrations of ZnCl2. Neurotoxic effects of ZnCl2 were observed with significant inhibition of acetylcholine (ACh) activity when the exposure dose was higher than 1 ppm. Furthermore, we found that zinc, metallothionein (MT), and cortisol levels in brain were elevated compared to the control group. A significantly negative correlation was observed between memory and acetylcholinesterase (AChE) activity. In summary, these findings revealed that exposure to ZnCl2 affected the behavior profile of zebrafish, and induced neurotoxicity which may be associated with damaged brain areas related to memory. Moreover, our ZnCl2-induced zebrafish model may have potential for AD-associated research in the future.

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