Loganin prevents BV-2 microglia cells from Aß1-42 -induced inflammation via regulating TLR4/TRAF6/NF-κB axis.

ABSTRACT

Neuroinflammation is closely related with the pathogenesis and progress of neurodegenerative diseases including Alzheimer's disease (AD). Loganin, an iridoid glycoside obtained from traditional Chinese medicine Cornus officinalis, has properties of inhibiting inflammation and improving memory. The present study was aimed to investigate effects of loganin on Aß-induced inflammation and to explore the underlying mechanisms. BV-2 microglia cells were stimulated with 10 µM Aß1-42 for 24 h to induce inflammatory damage. According to results of CCK-8 assay, the doses of loganin in present work were 10 and 30 µM. We found that treatment with loganin could inhibit Aß1-42 -induced microglia activation. Furthermore, loganin treatment prevented the over-production of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Macrophage Chemotactic Protein 1(MCP-1), Nitric oxide (NO), Prostaglandin E2 (PGE2) and the up-regulation of inducible nitric oxide synthase (iNOS) and Cyclooxygenase 2 (COX-2) in Aß1-42 -stimulated BV-2 cells. Results from Western blots demonstrated that loganin inhibited Aß1-42 -induced elevation in Toll-like receptor 4 (TLR4), Myeloid Differentiation Factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6). Loganin treatment also attenuated the increased phosphorylation level of IRAK4 caused by Aß1-42 . Additionally, loganin alleviated nuclear translocation of NF-κB p65 subunit in Aß1-42 -stimulated BV-2 cells, and this phenomenon could be reversed by TLR4 agonist LPS. Further, the anti-inflammatory effects of loganin were attenuated when TLR4 signaling pathway was re-activated by LPS. Taken together, our data indicated that loganin could attenuate inflammatory response induced by Aß in BV-2 microglia cells, partially through deactivating the TLR4/TRAF6/NF-κB axis.