Trilobatin Protects Against Aβ25–35-Induced Hippocampal HT22 Cells Apoptosis Through Mediating ROS/p38/Caspase 3-Dependent Pathway

Chen, Nana; Wang, Jiao; He, Yuqi; Xu, Yingshu; Zhang, Yuchuan; Gong, Qihai; Yu, Chunhao; Gao, Jianmei

doi:10.3389/fphar.2020.00584

Cited by 33 publications

(16 citation statements)

References 34 publications

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“…In the present study, we identified that TLB might alleviate Aβ deposition, Tau pathology, synaptic degeneration, glial In a recent study, Chen et al [26] showed that TLB protects HT22 cell death induced by Aβ 25-35 through the 10…”

Section: Discussionsupporting

confidence: 52%

Trilobatin Alleviates Cognitive Deficits and Pathologies in an Alzheimer’s Disease Mouse Model

Ding

Huang

Dai

et al. 2021

Oxidative Medicine and Cellular Longevity

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Alzheimer’s disease (AD) is the most common neurodegenerative disease nowadays that causes memory impairments. It is characterized by extracellular aggregates of amyloid-beta (Aβ), intracellular aggregates of hyperphosphorylated Tau (p-Tau), and other pathological features. Trilobatin (TLB), a natural flavonoid compound isolated from Lithocarpuspolystachyus Rehd., has emerged as a neuroprotective agent. However, the effects and mechanisms of TLB on Alzheimer’s disease (AD) remain unclear. In this research, different doses of TLB were orally introduced to 3×FAD AD model mice. The pathology, memory performance, and Toll-like receptor 4- (TLR4-) dependent inflammatory pathway protein level were assessed. Here, we show that TLB oral treatment protected 3×FAD AD model mice against the Aβ burden, neuroinflammation, Tau hyperphosphorylation, synaptic degeneration, hippocampal neuronal loss, and memory impairment. The TLR4, a pattern recognition immune receptor, has been implicated in neurodegenerative disease-related neuroinflammation. We found that TLB suppressed glial activation by inhibiting the TLR4-MYD88-NFκB pathway, which leads to the inflammatory factor TNF-α, IL-1β, and IL-6 reduction. Our study shows that TLR4 might be a key target of TLB in AD treatment and suggests a multifaceted target of TLB in halting AD. Taken together, our findings suggest a potential therapeutic effect of TLB in AD treatment.

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Section: Discussionsupporting

confidence: 52%

Trilobatin Alleviates Cognitive Deficits and Pathologies in an Alzheimer’s Disease Mouse Model

Ding

Huang

Dai

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Our findings indicate that cortical neurons exposed to Aβ 25-35 , a peptide broadly used in in vitro and in vivo models of AD [ 33 , 34 ], undergo a significant change in the signalling pathways mediated by different mGluRs and ARs, and a reduction in the cell viability. In brief, (i) density of Group I mGluR was increased at the plasma membrane together with an increase in mGluR 1 gene expression; however, the ability of these receptors to activate the PLC system resulted in being impaired.…”

Section: Discussionmentioning

confidence: 91%

Early Effects of the Soluble Amyloid β25-35 Peptide in Rat Cortical Neurons: Modulation of Signal Transduction Mediated by Adenosine and Group I Metabotropic Glutamate Receptors

Castillo

Ballesteros-Yáñez

León-Navarro

et al. 2021

IJMS

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The amyloid β peptide (Aβ) is a central player in the neuropathology of Alzheimer’s disease (AD). The alteration of Aβ homeostasis may impact the fine-tuning of cell signaling from the very beginning of the disease, when amyloid plaque is not deposited yet. For this reason, primary culture of rat cortical neurons was exposed to Aβ25-35, a non-oligomerizable form of Aβ. Cell viability, metabotropic glutamate receptors (mGluR) and adenosine receptors (AR) expression and signalling were assessed. Aβ25-35 increased mGluR density and affinity, mainly due to a higher gene expression and protein presence of Group I mGluR (mGluR1 and mGluR5) in the membrane of cortical neurons. Intriguingly, the main effector of group I mGluR, the phospholipase C β1 isoform, was less responsive. Also, the inhibitory action of group II and group III mGluR on adenylate cyclase (AC) activity was unaltered or increased, respectively. Interestingly, pre-treatment of cortical neurons with an antagonist of group I mGluR reduced the Aβ25-35-induced cell death. Besides, Aβ25-35 increased the density of A1R and A2AR, along with an increase in their gene expression. However, while A1R-mediated AC inhibition was increased, the A2AR-mediated stimulation of AC remained unchanged. Therefore, one of the early events that takes place after Aβ25-35 exposure is the up-regulation of adenosine A1R, A2AR, and group I mGluR, and the different impacts on their corresponding signaling pathways. These results emphasize the importance of deciphering the early events and the possible involvement of metabotropic glutamate and adenosine receptors in AD physiopathology.

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“…A similar result was observed in caspase-9 in which GM2 significantly restrained the activation of caspase-9 induced by MPP + ( Figure 3 D). Of note, caspase-3, an eventual protein in the apoptotic cascade that catalyzed the specific cleavage of multiple vital cellular proteins [ 33 ], was also reduced in response to the administration of GM2 in PC12 cells ( Figure 3 C), indicating that GM2 inhibits apoptosis in MPP + -induced PC12 cells.…”

Section: Resultsmentioning

confidence: 99%

Glucuronomannan GM2 from Saccharina japonica Enhanced Mitochondrial Function and Autophagy in a Parkinson’s Model

et al. 2021

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Parkinson’s disease (PD), one of the most common neurodegenerative disorders, is caused by dopamine depletion in the striatum and dopaminergic neuron degeneration in the substantia nigra. In our previous study, we hydrolyzed the fucoidan from Saccharina japonica, obtaining three glucuronomannan oligosaccharides (GMn; GM1, GM2, and GM3) and found that GMn ameliorated behavioral deficits in Parkinsonism mice and downregulated the apoptotic signaling pathway, especially with GM2 showing a more effective role in neuroprotection. However, the neuroprotective mechanism is unclear. Therefore, in this study, we aimed to assess the neuroprotective effects of GM2 in vivo and in vitro. We applied GM2 in 1-methyl-4-phenylpyridinium (MPP+)-treated PC12 cells, and the results showed that GM2 markedly improved the cell viability and mitochondrial membrane potential, inhibited MPP+-induced apoptosis, and enhanced autophagy. Furthermore, GM2 contributed to reducing the loss of dopaminergic neurons in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice through enhancing autophagy. These data indicate that a possible protection of mitochondria and upregulation of autophagy might underlie the observed neuroprotective effects, suggesting that GM2 has potential as a promising multifunctional lead disease-modifying therapy for PD. These findings might pave the way for additional treatment strategies utilizing carbohydrate drugs in PD.

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Trilobatin Protects Against Aβ25–35-Induced Hippocampal HT22 Cells Apoptosis Through Mediating ROS/p38/Caspase 3-Dependent Pathway

Cited by 33 publications

References 34 publications

Trilobatin Alleviates Cognitive Deficits and Pathologies in an Alzheimer’s Disease Mouse Model

Trilobatin Alleviates Cognitive Deficits and Pathologies in an Alzheimer’s Disease Mouse Model

Early Effects of the Soluble Amyloid β25-35 Peptide in Rat Cortical Neurons: Modulation of Signal Transduction Mediated by Adenosine and Group I Metabotropic Glutamate Receptors

Glucuronomannan GM2 from Saccharina japonica Enhanced Mitochondrial Function and Autophagy in a Parkinson’s Model

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