Hydroxy-safflor yellow A attenuates Aβ1-42-induced inflammation by modulating the JAK2/STAT3/NF-κB pathway

• HSYA ameliorated the memory deficits in Aβ1–42-induced AD mice.
• HSYA suppressed inflammatory responses in Aβ1–42-induced AD mice.
• The anti-inflammatory effect of HSYA was mediated by a novel JAK2-STAT3-NF-κB pathway.

Beta-amyloid (Aβ)-mediated inflammation plays a critical role in the initiation and progression of Alzheimer׳s disease (AD). Anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of hydroxy-safflor yellow A (HSYA) on Aβ1–42-induced inflammation in AD mice was investigated and the underlying mechanisms were explored. Aβ1–42 was injected into bilateral hippocampi of mice to induce AD models in vivo. Spatial learning and memory of mice were investigated by the Morris water maze test. Activated microglia and astrocytes were examined by immunofluorescence staining for ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). The mRNA of inflammatory cytokines were measured using real-time PCR. NF-κB p65 translocation was analyzed by western blotting and immunostaining. IκB and phosphorylation of JAK2 and STAT3 were tested by western blotting. The results showed that HSYA ameliorated the memory deficits in Aβ1–42-induced AD mice. HSYA suppressed Aβ1–42-induced activation of microglia and astrocytes and reduced the mRNA expression of pro-inflammatory mediators. HSYA up-regulated the JAK2/STAT3 pathway and inhibits the activation of NF-κB signaling pathways. Pharmacological inhibition of STAT3 by AG490 reversed the inactivation of p65 and anti-inflammatory effects of HSYA. In conclusion, these results suggest that HSYA protects Aβ1–42-induced AD model through inhibiting inflammatory response, which may involve the JAK2/STAT3/NF-κB pathway.