Targeting the TLR4/NF-κB pathway in β-amyloid-stimulated microglial cells: A possible mechanism that oxysophoridine exerts anti-oxidative and anti-inflammatory effects in an in vitro model of Alzheimer's disease

Abstract

β-amyloid (Aβ) accumulation is a major neuropathological characteristic of Alzheimer's disease (AD) and serves as an inflammatory stimulus for microglial cells. Oxysophoridine has multiple pharmacological effects, including anti-inflammatory and anti-oxidative activities. In view of this, the current study aimed to investigate the effects of oxysophoridine on Aβ-induced activation of microglial BV-2 cells. Cell Counting Kit-8 assay showed that oxysophoridine concentration-dependently attenuated Aβ-induced viability reduction of BV-2 cells. Aβ stimulation reduced the activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) and elevated malondialdehyde (MDA) content in BV-2 cells, but these effects were attenuated by oxysophoridine. Oxysophoridine abolished Aβ-induced increase of mRNA expression, secretion, and protein expression of tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) in BV-2 cells. Additionally, western blot suggested that oxysophoridine inhibited Aβ-induced activation of the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) pathways in BV-2 cells. Inhibition of the TLR4/NF-κB pathway by TAK-242 enhanced the effects of oxysophoridine on Aβ-induced viability reduction, oxidative stress, and inflammation in BV-2 cells. Taken together, oxysophoridine suppressed Aβ-induced oxidative stress and inflammation in BV-2 cells by inhibition of the TLR4/NF-κB pathway.

Keywords: Alzheimer’s disease; Inflammation; Oxidative stress; Oxysophoridine; TLR4/NF-κB pathway; β-Amyloid.