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Published on: March 21, 2017
Polyphenols Derived from Lychee Seed Suppress Aβ (1-42)-Induced Neuroinflammation
Yong Tang1, Rui Xiong2, An-Guo Wu3,4
1Laboratory of Chinese Materia Medica, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China. tangy1989@yeah.net.
Abstract:
Amyloid-β (Aβ) is commonly recognized as the most important factor that results in neuronal cell death and accelerates the progression of Alzheimer's disease (AD). Increasing evidence suggests that microglia activated by Aβ release an amount of neurotoxic inflammatory cytokines that contribute to neuron death and aggravate AD pathology. In our previous studies, we found that lychee seed fraction (LSF), an active fraction derived from the lychee seed, could significantly improve the cognitive function of AD rats and inhibit Aβ-induced neuroinflammation in vitro, and decrease neuronal injuries in vivo and in vitro. In the current study, we aimed to isolate and identify the specific components in LSF that were responsible for the anti-neuroinflammation effect using preparative high performance liquid chromatography (pre-HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) methods. To this end, we confirmed two polyphenols including catechin and procyanidin A2 that could improve the morphological status of BV-2 cells and suppress the release, mRNA levels, and protein expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through downregulating the nuclear factor-κB (NF-κB) signaling pathway using ELISA, RT-PCR, and Western blotting methods. Furthermore, catechin and procyanidin A2 could inhibit Aβ-induced apoptosis in BV-2 cells by upregulating Bcl-2 and downregulating Bax protein expression. Therefore, the current study illustrated the active substances in lychee seed, and first reported that catechin and procyanidin A2 could suppress neuroinflammation in Aβ-induced BV-2 cells, which provides detailed insights into the molecular mechanism of catechin and procyanidin A2 in the neuroprotective effect, and their further validations of anti-neuroinflammation in vivo is also essential in future research.
Insights
Lychee seed compounds, catechin and procyanidin A2, reduce neuroinflammation and cell death linked to Alzheimer's disease by targeting key inflammatory pathways.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Amyloid-β (Aβ) accumulation drives Alzheimer's disease (AD) pathology.
- Activated microglia release neurotoxic cytokines, exacerbating neuronal damage in AD.
- Lychee seed fraction (LSF) previously showed neuroprotective effects in AD models.
Purpose of the Study:
- To identify specific anti-neuroinflammatory compounds within LSF.
- To elucidate the molecular mechanisms underlying LSF's neuroprotective effects.
Main Methods:
- Preparative HPLC, LC-MS, and NMR for compound isolation and identification.
- ELISA, RT-PCR, and Western blotting to assess cytokine and signaling pathway modulation.
- BV-2 microglial cell models exposed to Aβ to mimic AD neuroinflammation.
Main Results:
- Catechin and procyanidin A2 were identified as key active compounds in LSF.
- These polyphenols suppressed Aβ-induced release and expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).
- The anti-inflammatory effect was mediated by downregulating the NF-κB signaling pathway.
- Catechin and procyanidin A2 inhibited Aβ-induced apoptosis by modulating Bcl-2 and Bax expression.
Conclusions:
- Catechin and procyanidin A2 are the primary active components in LSF responsible for anti-neuroinflammatory effects.
- These compounds offer neuroprotection by suppressing microglial activation and apoptosis in an Aβ-induced AD model.
- Further in vivo validation is warranted to confirm the therapeutic potential of catechin and procyanidin A2 for Alzheimer's disease.
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