Polyphenols Derived from Lychee Seed Suppress Aβ (1-42)-Induced Neuroinflammation

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.

Neuroprotection of Tropical Fruit Juice Mixture via the Reduction of iNOS Expression and CRH Level in β‐Amyloid‐Induced Rats Model of Alzheimer’s Disease

“…Our current findings demonstrated that Aβ infussion can induce the expression of iNOS, and supplementation with the tropical fruit juice mixture can attenuate the induction of iNOS expression by Aβ. is observation was supported by previous findings where supplementation with polyphenols derived from lychee seed and resveratrol was able to reduce the iNOS expression in rats following Aβ induction [26,55].…”

Procyanidin A2, a polyphenolic compound, exerts anti-inflammatory and anti-oxidative activity in lipopolysaccharide-stimulated RAW264.7 cells

“…PCA2 exhibited anti-inflammatory activity via suppressing CCL-26 production in IL-4-stimulated A549 cells [24] and anti-oxidative activity via modulating the Nrf2 pathway in tert-butyl hydroperoxide-stimulated L0-2 cells [35]. PCA2 has a neuroprotective effect on Aβ-stimulated BV2 cells [36]. However, the detailed mechanism of PCA2's anti-inflammatory and anti-oxidative activity is still uncertain.…”

“…On the other hand, LPS-stimulated macrophage is a classic model of inflammatory responses in vitro [ 33 ]. Previous studies revealed that PCA2 has the effects of protecting cells from oxidation, inflammation, such as human monocyte macrophages (THP-1) [ 26 ] and L0-2 cells [ 35 ], A549 cells [ 24 ], and BV2 cells [ 36 ], respectively. PCA2 exhibited anti-inflammatory activity via suppressing CCL-26 production in IL-4-stimulated A549 cells [ 24 ] and anti-oxidative activity via modulating the Nrf2 pathway in tert -butyl hydroperoxide-stimulated L0-2 cells [ 35 ].…”

Lychee seed polyphenol protects theblood–brainbarrier through inhibiting Aβ(25–35)‐inducedNLRP3inflammasome activation via theAMPK/mTOR/ULK1‐mediatedautophagy inbEnd.3 cells andAPP/PS1mice

“…belonging to the Sapindaceae family) and prescribed in various Chinese medical formulas in clinical practice. Our previous studies have clarified that the main components in lychee seed are polyphenols, including rutin, quercetin, catechin, and proanthocyanidins (Tang et al, 2018; Xiong et al, 2020; Zhao et al, 2018). Further study found that these polyphenols in lychee seed (LSP) could inhibit Aβ‐induced apoptosis in neuronal cells and the neuroinflammatory response in microglia via the NF‐κB pathway (Tang et al, 2018; Zhao et al, 2018).…”

“…Our previous studies have clarified that the main components in lychee seed are polyphenols, including rutin, quercetin, catechin, and proanthocyanidins (Tang et al, 2018; Xiong et al, 2020; Zhao et al, 2018). Further study found that these polyphenols in lychee seed (LSP) could inhibit Aβ‐induced apoptosis in neuronal cells and the neuroinflammatory response in microglia via the NF‐κB pathway (Tang et al, 2018; Zhao et al, 2018). In this study, LSP was prepared as previously described (Wang, Wu, et al, 2017; Wang, Zhang, et al, 2017), then we investigated the protective effect of LSP on BBB integrity.…”