Epigallocatechin-3-gallate rescues LPS-impaired adult hippocampal neurogenesis through suppressing the TLR4-NF-κB signaling pathway in mice

Abstract

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activatingTLR4-NF-κB signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-κB pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPSinduced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.

Anti-oxidant and anti-inflammatory effects of rice bran and green tea fermentation mixture on lipopolysaccharideinduced RAW 264.7 macrophages

“…We observed that the production of NO and iNOS in LPS-induced murine macrophages was reduced by OCB treatment. During inflammation, macrophages have three major functions: antigen presentation [14], phagocytosis [15], and immunomodulation [15,16], which is mediated through the production of various cytokines and growth factors. The inflammatory process is usually tightly regulated, involving both signals that initiate and maintain inflammation and signals that resolve inflammation.…”

Catechins reduce inflammation in lipopolysaccharide‐stimulated dental pulp cells by inhibiting activation of the NF‐κB pathway

“…Nakanishi and co‐workers showed that catechins can inhibit VEGF production and COX‐2 expression in HDPCs. Catechins have also been reported to have potential effects on suppressing inflammation mediated by the NF‐κB pathway (Ravindranath & Ravindranath, ), especially in lipopolysaccharide‐mediated cerebral injury (Seong et al, ). Hirao and colleagues reported that catechins can reduce inflammatory reactions via MAPK pathways in dental pulp cells and that up‐regulated expression of IL‐8 or prostaglandin‐E2 in streptococci could be inhibited by catechins (Hirao et al, ).…”

Recent Advances on the Anti-Inflammatory and Antioxidant Properties of Red Grape Polyphenols: In Vitro and In Vivo Studies

“…RES was shown to attenuate LPS and Aβ-mediated microglia neuroinflammation, inhibiting the TLR-4/NF-κB/STAT pathway [180]. EGCG was able to abrogate LPS-impaired adult hippocampal neurogenesis, silencing the TLR-4 signaling in mice [181][182][183].…”