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

beta-amyloid (A beta) accumulation is a major neuropathological characteristic of Alzheimer's disease (AD) and serves as an inflammatory stimulus for micmglial 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 A beta-induced activation of microglial BV-2 cells. Cell Counting Kit-8 assay showed that oxysophoridine concentration-dependently attenuated A beta-induced viability reduction of BV-2 cells. A beta 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 A beta-induced increase of mRNA expression, secretion, and protein expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in BV-2 cells. Additionally, western blot suggested that oxysophoridine inhibited A beta-induced activation of the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B) pathways in BV-2 cells. Inhibition of the TLR4/NF-kappa B pathway by TAK-242 enhanced the effects of oxysophoridine on A beta-induced viability reduction, oxidative stress, and inflammation in BV-2 cells. Taken together, oxysophoridine suppressed A beta-induced oxidative stress and inflammation in BV-2 cells by inhibition of the TLR4/NF-kappa B pathway.

Automated summary

Oxysophoridine suppresses A beta-induced oxidative stress and inflammation in BV-2 cells by inhibiting the TLR4/NF-kappa B pathway.