scholarly journals Tetramethylpyrazine Derivative T-006 Ameliorates the Amyloid-β Plagues of Transgenic Alzhermer's Mice by Modulation of TLR4-mediated MyD88/NF-κB Signaling

2021 ◽  
Author(s):  
Haiyun Chen ◽  
Xiao Chang ◽  
Jiemei Zhou ◽  
Guiliang Zhang ◽  
Jiehong Cheng ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Trigger Factor ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
Bv2 Microglial 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.

scholarly journals Neuropharmacological Effects of Quercetin: A Literature-Based Review

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.

scholarly journals Tongxinluo Exerts Inhibitory Effects on Pyroptosis and Amyloid-β Peptide Accumulation after Cerebral Ischemia/Reperfusion in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Bing Wang ◽  
Zhongkuan Lyu ◽  
Yuanjin Chan ◽  
Qiyue Li ◽  
Li Zhang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Glymphatic System ◽  
Pyrin Domain ◽  
Cerebral Ischemia Reperfusion ◽  
Potential Possibility ◽  
Important Pathway

Amyloid-β peptide (Aβ) accumulation is a detrimental factor in cerebral ischemia/reperfusion (I/R) injuries accounting for dementia induced by ischemic stroke. In addition to blood brain barrier (BBB), the glymphatic system mediated by aquaporin-4 (AQP-4) on astrocytic endfeet functions as an important pathway for the clearance of Aβ in the brain. Cerebral I/R induced astrocytic pyroptosis potentially causes the AQP-4 polarization loss and dysfunctional BBB-glymphatic system exacerbating the accumulation of Aβ. Furthermore, Aβ toxicity has been identified as a trigger of pyroptosis and BBB damage, suggesting an amplified effect of Aβ accumulation after cerebral I/R. Therefore, based on our previous work, this study was designed to explore the intervention effects of Tongxinluo (TXL) on astrocytic pyroptosis and Aβ accumulation after cerebral I/R in rats. The results showed that TXL intervention obviously alleviated the degree of pyroptosis by downregulating expression levels of cleaved caspase-11/1, N-terminal gasdermin D, nucleotide-binding oligomerization domain-like receptors pyrin domain containing 3 (NLRP3), interleukin-6 (IL-6), and cleaved IL-1β and abated astrocytic pyroptosis after cerebral I/R. Moreover, TXL intervention facilitated to restore AQP-4 polarization and accordingly relieve Aβ accumulation around astrocytes in ischemic cortex and hippocampus as well as the formation of toxic Aβ (Aβ1–42 oligomer). Our study indicated that TXL intervention could exert protective effects on ischemic brain tissues against pyroptotic cell death, inhibit astrocytic pyroptosis, and reduce toxic Aβ accumulation around astrocytes in cerebral I/R injuries. Furthermore, our study provides biological evidence for the potential possibility of preventing and treating poststroke dementia with TXL in clinical practice.

Echinacoside ameliorates the memory impairment and cholinergic deficit induced by amyloid beta peptides via the inhibition of amyloid deposition and toxicology

2017 ◽  
Vol 8 (6) ◽  
pp. 2283-2294 ◽  
Author(s):  
Young-Ji Shiao ◽  
Muh-Hwan Su ◽  
Hang-Ching Lin ◽  
Chi-Rei Wu
Keyword(s):  
Amyloid Beta ◽  
Memory Impairment ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Neuronal Function ◽  
Amyloid Beta Peptides ◽  
Beta Peptides ◽  
Amyloid Cascade

This study investigates the role of the amyloid cascade and central neuronal function on the protective effects of echinacoside in amyloid β peptide 1-42 (Aβ 1-42)-treated SH-SY5Y cells and an Aβ 1-42-infused rat.

P1-018: Protective effects of pre--germinated brown rice extract against amyloid β-Peptide (1-42) -induced apoptosis in neuronal SK-N-SH cells

2011 ◽  
Vol 7 ◽  
pp. S117-S117
Author(s):  
Rungtip Soi-ampornkul ◽  
Sarawut Junnu ◽  
Surin Kanyok ◽  
Sompong Liammongkolkul ◽  
Wanphen Katunyoo ◽  
...  
Keyword(s):  
Brown Rice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Germinated Brown Rice ◽  
Induced Apoptosis

Protective effects of S-nitrosoglutathione against amyloid β-peptide neurotoxicity

2005 ◽  
Vol 38 (7) ◽  
pp. 938-949 ◽  
Author(s):  
Tzyh-Chwen Ju ◽  
Shang-Der Chen ◽  
Chia-Chin Liu ◽  
Ding-I Yang
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Protective Effects

Protective effects and potential underlying mechanisms of sodium copper chlorophyllin against ethanol-induced gastric ulcer in mice

2019 ◽  
Vol 51 (9) ◽  
pp. 925-933 ◽  
Author(s):  
Huawei Lv ◽  
Yan Lin ◽  
Peigang Liu ◽  
Weiqing Liang ◽  
Kemin Wei ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Nuclear Translocation ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Cytokine Analysis ◽  
Apoptotic Protein ◽  
Tnf Α ◽  
Injury Treatment ◽  
Underlying Mechanisms ◽  
Sodium Copper Chlorophyllin

Abstract In study, we aimed to determine the mechanisms underlying the gastroprotective effects of sodium copper chlorophyllin (SCC) against ethanol-induced gastric ulcer injury in mice. First, the gastroprotective effects of SCC against gastric ulcer induced by ethanol were assessed. Then, biochemical, histopathological, immunohistochemistry assays, and western blot analysis were conducted to determine the possible mechanisms of action underlying the effects of SCC. Compared to the effects of omeprazole (OME) in a confirmed mouse model of ethanol-induced gastric ulcer injury, treatment with various doses of SCC resulted in up-regulation of Bcl-2 and down-regulation of the pro-apoptotic protein Bax. Significant decreases in the levels of the malondialdehyde (MDA), myeloperoxidase (MPO), and NO in the gastric tissues were observed. Furthermore, inflammatory cytokine analysis revealed that SCC treatment inhibited the expressions of TNF-α and IL-6, greatly reduced the phosphorylation level of IκB, and repressed the nuclear translocation of NF-κB p65, which demonstrated that SCC inhibited the activation of the NF-κB pathway. The present findings suggest that the protective effects of SCC may be beneficial as a potential preventive and therapeutic agent for gastric ulcer through the NF-κB pathway. Taken together, SCC administration significantly decreased the levels of MPO, NO, and MDA in gastric tissue and exerted a powerful anti-inflammatory activity as demonstrated by reduction in the secretions of proinflammatory mediators such as IL-6 and TNF-α in the serum of mice exposed to ethanol.

scholarly journals Neuroprotective Action of Human Wharton’s Jelly-Derived Mesenchymal Stromal Cell Transplants in a Rodent Model of Stroke

2018 ◽  
Vol 27 (11) ◽  
pp. 1603-1612 ◽  
Author(s):  
Kuo-Jen Wu ◽  
Seong-Jin Yu ◽  
Chia-Wen Chiang ◽  
Yu-Wei Lee ◽  
B Linju Yen ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Neuroprotective Effect ◽  
Brain Infarction ◽  
Hippocampal Slices ◽  
Wharton’S Jelly ◽  
Trophic Factors ◽  
Neurological Deficits ◽  
Protective Effects ◽  
Wharton's Jelly ◽  
Host Brain

Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) have distinct immunomodulatory and protective effects against kidney, liver, or heart injury. Limited studies have shown that WJ-MSCs attenuates oxygen–glucose deprivation-mediated inflammation in hippocampal slices. The neuroprotective effect of intracerebral WJ-MSC transplantation against stroke has not been well characterized. The purpose of this study was to examine the neuroprotective effect of human WJ-MSC (hWJ-MSC) transplants in an animal model of stroke. Adult male Sprague–Dawley rats were anesthetized and placed in a stereotaxic frame. hWJ-MSCs, pre-labeled with chloromethyl benzamide 1,1’-dioctadecyl-3,3,3’3’- tetramethylindocarbocyanine perchlorate (CM-Dil), were transplanted to the right cerebral cortex at 10 min before a transient (60 min) right middle cerebral artery occlusion (MCAo). Transplantation of hWJ-MSCs significantly reduced neurological deficits at 3 and 5 days after MCAo. hWJ-MSC transplants also significantly reduced brain infarction and microglia activation in the penumbra. Grafted cells carrying CM-Dil fluorescence were identified at the grafted site in the ischemic core; these cells were mostly incorporated into ionized calcium-binding adaptor molecule (+) cells, suggesting these xenograft cells were immuno-rejected by the host. In another set of animals, hWJ-MSCs were transplanted in cyclosporine (CsA)-treated rats. hWJ-MSC transplants significantly reduced brain infarction, improved neurological function, and reduced neuroinflammation. Less phagocytosis of CM-dil-labeled grafted cells was found in the host brain after CsA treatment. Transplantation of hWJ-MSC significantly increased glia cell line-derived neurotrophic factor expression in the host brain. Taken together, our data support that intracerebral transplantation of hWJ-MSCs reduced neurodegeneration and inflammation in the stroke brain. The protective effect did not depend on the survival of grafted cells but may be indirectly mediated through the production of protective trophic factors from the transplants.

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