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Epigallocatechin‐3‐Gallate Attenuates Microglial Inflammation and Neurotoxicity by Suppressing the Activation of Canonical and Noncanonical Inflammasome via TLR4/NF‐κB Pathway
Author(s) -
Zhong Xin,
Liu Mingyan,
Yao Weifan,
Du Ke,
He Miao,
Jin Xin,
Jiao Linchi,
Ma Guowei,
Wei Binbin,
Wei Minjie
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201801230
Subject(s) - inflammasome , microglia , neurotoxicity , neuroprotection , chemistry , tlr4 , inflammation , caspase 1 , nf κb , neuroinflammation , pharmacology , microbiology and biotechnology , receptor , signal transduction , biochemistry , biology , immunology , toxicity , organic chemistry
Scope In this study, it has been investigated whether the neuroprotective efficacy of epigallocatechin‐3‐gallate (EGCG) is mediated by inhibition of canonical and noncanonical inflammasome activation via toll‐like receptor 4 (TLR4)/NF‐κB pathway both in LPS+Aβ‐induced microglia in vitro and in APP/PS1 mice in vivo. Methods and results In BV2 cells, EGCG inhibits the expressions of Iba‐1, cleaved IL‐1β, and cleaved IL‐18 induced by LPS+Aβ. Then, the supernatants are used to treat SH‐SY5Y cells, and EGCG treatment significantly recovers the neurotoxicity from LPS+Aβ‐induced microglial conditioned media. Subsequently, it has been found that EGCG reduces the microglial expressions of caspase‐1 p20, NLRP3, and caspase‐11 p26. Furthermore, the expression levels of Toll‐like receptor 4 (TLR4), p‐IKK/IKK, and p‐NF‐κB/NF‐κB were decreased after EGCG treatment. As expected, when a caspase‐1 specific inhibitor Z‐YVAD‐FMK, and an IKK and caspase‐11 inhibitor wedelolactone are used for blocking, Z‐YVAD‐FMK and wedelolactone exacerbate the inhibitory efficacy than using EGCG alone. Finally, consistent with the results obtained in BV2 cells, EGCG treatment reduces microglial inflammation and neurotoxicity by suppressing the activation of canonical NLRP3 and noncanonical caspase‐11‐dependent inflammasome via TLR4/NF‐κB pathway in LPS+Aβ‐induced rat primary microglia and hippocampus of APP/PS1 mice. Conclusion EGCG attenuates microglial inflammation and neurotoxicity by inhibition of canonical NLRP3 and noncanonical caspase‐11‐dependent inflammasome activation via TLR4/NF‐κB pathway.