Neuroprotective Effect of Ganglioside GM1 on the Cytotoxic Action of Hydrogen Peroxide and Amyloid β-peptide in PC12 cells

Abstract BackgroundMicroglial activation mediated neuroinflammation was considered as a vital trigger factor in the pathogenesis of Alzheimer’s disease (AD). T-006, a new tetramethylpyrazine derivative, has been recently found to alleviate cognitive deficits via inhibition of Tau expression and phosphorylation in AD transgenic mouse models. Here, we hypothesized that T-006 may ameliorate AD-like pathology by suppressing the neuroinflammation. MethodsAPP/PS1 transgenic AD mouse model was used here to evaluate the anti-inflammatory effect of T-006 and its underlying mechanisms, as well as its potential protective effects against lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity.ResultsOur results indicated that T-006 significantly decreased the levels of total amyloid β peptide (Aβ) and glial fibrillary acidic protein (GFAP) as well as the ionized calcium binding adaptor molecule-1 (Ibα-1) expression in the APP/PS1 mice. Moreover, T-006 dramatically suppressed abnormal elevation of inflammatory mediators and reduced the levels of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88) and NF-κB signaling related proteins in lipopolysaccharide (LPS)-induced BV2 microglial cells. We also found that TAK242, a TLR4 inhibitor could abolish the down-regulation of T-006 on LPS-induced proinflammatory mediators and reversed the downstream proteins expression containing MyD88 and NF-κB signaling. Importantly, T-006 prevented against neuroinflammation induced neurotoxicity by mitigating reactive oxygen species (ROS) overproduction and mitochondrial membrane potential (MMP) dissipation. Conclusions T-006 exerts neuroprotective effect in treating AD by suppressing the neuroinflammation through modulation of TLR4-mediated MyD88/NF-κB signaling pathways.

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Neuropharmacological Effects of Quercetin: A Literature-Based Review

Frontiers in Pharmacology ◽

10.3389/fphar.2021.665031 ◽

2021 ◽

Vol 12 ◽

Author(s):

Md. Shahazul Islam ◽

Cristina Quispe ◽

Rajib Hossain ◽

Muhammad Torequl Islam ◽

Ahmed Al-Harrasi ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Neuroprotective Effect ◽

Animal Experiments ◽

Amyloid Β ◽

Neuronal Injury ◽

Amyloid Β Peptide ◽

Protective Effects ◽

Neuroprotective Effects

Quercetin (QUR) is a natural bioactive flavonoid that has been lately very studied for its beneficial properties in many pathologies. Its neuroprotective effects have been demonstrated in many in vitro studies, as well as in vivo animal experiments and human trials. QUR protects the organism against neurotoxic chemicals and also can prevent the evolution and development of neuronal injury and neurodegeneration. The present work aimed to summarize the literature about the neuroprotective effect of QUR using known database sources. Besides, this review focuses on the assessment of the potential utilization of QUR as a complementary or alternative medicine for preventing and treating neurodegenerative diseases. An up-to-date search was conducted in PubMed, Science Direct and Google Scholar for published work dealing with the neuroprotective effects of QUR against neurotoxic chemicals or in neuronal injury, and in the treatment of neurodegenerative diseases. Findings suggest that QUR possess neuropharmacological protective effects in neurodegenerative brain disorders such as Alzheimer’s disease, Amyloid β peptide, Parkinson’s disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. In summary, this review emphasizes the neuroprotective effects of QUR and its advantages in being used in complementary medicine for the prevention and treatment o of different neurodegenerative diseases.

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