Lychee seed polyphenol inhibits Aβ-induced activation of NLRP3 inflammasome via the LRP1/AMPK mediated autophagy induction

Qiu, Wen-Qiao; Pan, Rong; Tang, Yong; Zhou, Xiao-Gang; Wu, Jianming; Yu, Lu; Law, Betty Yuen‐Kwan; Ai, Wei; Yu, Chong-Lin; Qin, Da-Lian; Wu, Anguo

doi:10.1016/j.biopha.2020.110575

Cited by 52 publications

(40 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of PGC-1α is affected by upstream pathway proteins, such as AMPK. AMPK is a key protein for the maintenance of cellular homeostasis ( Qiu et al, 2020 ), playing various roles in promoting M2 polarization of microglia ( Chu et al, 2019 ). It modulates metabolic pathways in cells ( Szewczuk et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease

Chen

Jiang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most frequent type of dementia. Acteoside (ACT) is a compound isolated from Cistanche tubulosa, which possesses excellent neuroprotective properties. However, the underlying mechanism of ACT in regulating microglia polarization remains ill-defined. Therefore, a computational network model was established to identify the driving targets of ACT and predict its mechanism by integrating multiple available databases. The AlCl3-induced AD model in zebrafish larvae was successfully constituted to demonstrate the therapeutic efficacy of ACT. Subsequently, LPS-induced BV-2 cells uncovered the positive role of ACT in M1/M2 polarization. The NF-κB and AMPK pathways were further confirmed by transcriptomic analysis, metabolomics analysis, molecular biology techniques, and molecular docking. The research provided an infusive mechanism of ACT and revealed the connection between metabolism and microglia polarization from the perspective of mitochondrial function. More importantly, it provided a systematic and comprehensive approach for the discovery of drug targets, including the changes in genes, metabolites, and proteins.

show abstract

Section: Discussionmentioning

confidence: 99%

An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease

Chen

Jiang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…The expression of PGC-1α is affected by upstream pathway proteins, such as AMPK. AMPK is the key protein for the maintenance of cellular homeostasis [31] , playing various roles in promoting M2 polarization of microglia [32] . It modulates metabolic pathways in cells [33] .…”

Section: Discussionmentioning

confidence: 99%

Acteoside Repressed Microglia M1 Polarization Through Inhibited NF-κB Signalling Pathway and AMPK-Mediated Mitochondria Function Recovery

Chen

Jiang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Alzheimer's disease (AD) is the most frequent type of dementia. While acteoside (ACT), a compound isolated from Cistanche tubulosa, possesses neuroprotective properties. However, the underlying mechanism in regulating microglia polarization remains ill-defined. Methods: Herein, AlCl3-induced AD model in zebrafish larvae was applied to uncover the therapeutic efficacy of ACT. BV-2 cells were used to demonstrate the role of ACT on microglia polarization. RNA-Sequence, HPLC-Q-TOF-MS, western blot and molecular docking were combined to confirm its mechanism. Results: ACT significantly ameliorated the experimental dyskinesia and nervous system disorders in zebrafish. Subsequently, it suppressed M1 polarization and promoted to the M2 phenotype in LPS-induced BV-2 cells. We first demonstrated that ACT exerted profound transcriptomic impact, which involved regulation of key signaling pathways in inflammation, arginine biosynthesis, as well as pantothenate and CoA biosynthesis, correlating with mitochondria function. ACT treatment reduced microglia M1 polarization by inhibiting the NF-κB signalling pathway. And the metabolic pathways were further confirmed by HPLC-Q-TOF-MS. In addition, ACT rectified excessive ROS to restore mitochondria function through AMPK-mediated PGC-1α and UCP-2 upregulation, consistent with metabolic changes. Intriguingly, ACT may directly bind to both NF-κB and AMPKα, as evidenced by molecular docking. Conclusions: The research provided an infusive mechanism of ACT and illustrated a new perspective based on mitochondrial dysfunction to reveal the connection between metabolism and microglia polarization.

show abstract

“…In another study, LSPs also suppressed activation of the NLRP3 inflammasome by inhibiting the expression of NLRP3 and ASC, the cleavage of caspase-1, and the release of IL-1β in Aβ 1-42 -induced BV-2 cells and recovered PC-12 cells that were induced by incubated medium from Aβ 1-42 -treated BV-2 cells. Moreover, LSPs improved cognitive function and inhibited NLRP3 inflammasome activation in APP/PS1 mice [40,41].…”

Section: Natural Extraction Treatment Studies For Nlrp3 Inflammasome Regulation In Admentioning

confidence: 94%

A Novel Treatment Strategy by Natural Products in NLRP3 Inflammasome-Mediated Neuroinflammation in Alzheimer’s and Parkinson’s Disease

Lee

Kim

et al. 2021

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases. Many studies have demonstrated that the release of NLRP3 inflammasome-mediated proinflammatory cytokines by the excessive activation of microglia is associated with the pathogenesis of AD and PD and suggested that the NLRP3 inflammasome plays an important role in AD and PD development. In both diseases, various stimuli, such as Aβ and α-synuclein, accelerate the formation of the NLRP3 inflammasome in microglia and induce pyroptosis through the expression of interleukin (IL)-1β, caspase-1, etc., where neuroinflammation contributes to gradual progression and deterioration. However, despite intensive research, the exact function and regulation of the NLRP3 inflammasome has not yet been clearly identified. Moreover, there have not yet been any experiments of clinical use, although many studies have recently been conducted to improve treatment of inflammatory diseases using various inhibitors for NLRP3 inflammasome pathways. However, recent studies have reported that various natural products show improvement effects in the in vivo models of AD and PD through the regulation of NLRP3 inflammasome assembly. Therefore, the present review provides an overview of natural extraction studies aimed at the prevention or treatment of NLRP3 inflammasome-mediated neurological disorders. It is suggested that the discovery and development of these various natural products could be a potential strategy for NLRP3 inflammasome-mediated AD and PD treatment.

show abstract

Lychee seed polyphenol inhibits Aβ-induced activation of NLRP3 inflammasome via the LRP1/AMPK mediated autophagy induction

Cited by 52 publications

References 77 publications

An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease

An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease

Acteoside Repressed Microglia M1 Polarization Through Inhibited NF-κB Signalling Pathway and AMPK-Mediated Mitochondria Function Recovery

A Novel Treatment Strategy by Natural Products in NLRP3 Inflammasome-Mediated Neuroinflammation in Alzheimer’s and Parkinson’s Disease

Contact Info

Product

Resources

About