Inhibitory effect of ent-Sauchinone on amyloidogenesis via inhibition of STAT3-mediated NF-κB activation in cultured astrocytes and microglial BV-2 cells

Background: ent-sauchinone is a polyphenolic compound found in plants belonging to the lignan family. ent-sauchinone has been shown to modulate the expression of inflammatory factors through the nuclear factor-kappa b (nf-κb) signaling pathway. it is well known that neuroinflammation is associated with amyloidogenesis. thus,in the present study,we investigated whether ent-sauchinone could have anti-amyloidogenic effects through the inhibition of nf-κb pathways via its anti-inflammatory property.methods: to investigate the potential effect of ent-sauchinone on anti-neuroinflammation and anti-amyloidogenesis in in vitro studies,we used microglial bv-2 cells and cultured astrocytes treated with ent-sauchinone (1,5,and 10 μm) for 24 hours. for the detection of anti-neuro-inflammatory responses,reative oxygen species (ros) and nitric oxide (no) generation and inducible nitric oxide synthase (inos) and cyclooxygenase-2 (cox-2) expression were measured with assay kits and western blotting. β-secretase and β-secretase activities and β-amyloid levels were determined for measuring the anti-amyloidogenic effects of ent-sauchinone by enzyme assay kits. nf-κb and stat3 signals were detected with electromobility shift assay (emsa) to study the related signaling pathways. the binding of ent-sauchinone to stat3 was evaluated by a pull-down assay and by a docking model using autodock vina software (hoover's inc.,texas,united states).results:ent-sauchinone (1,5,and 10 μm) effectively decreased lipopolysaccharide (lps)-(1 μg/ml) induced inflammatory responses through the reduction of ros and no generations and inos and cox-2 expressions in cultured astrocytes and microglial bv-2 cells. ent-sauchinone also inhibited lps-induced amyloidogenesis through the inhibition of β-secretase and β-secretase activity. nf- κb amyloid and stat3,critical transcriptional factors regulating not only inflammation but also amyloidogenesis,were also inhibited in a concentration dependent manner by ent-sauchinone by blocking the phosphorylation of i κb and stat3 in cultured astrocytes and microglial bv-2 cells. the docking model approach showed that ent-sauchinone binds to stat3,and the employment of a stat3 inhibitor and sirna reversed ent-sauchinone-induced inhibition nf-κb activation and aβ generation.conclusions: these results indicated that ent-sauchinone inhibited neuroinflammation and amyloidogenesis through the inhibition of stat3-mediated nf-κb activity,and thus could be applied in the treatment of neuro-inflammatory diseases,including alzheimer's disease. © 2014 song et al.; licensee biomed central ltd.