Hydroxy-safflor yellow A inhibits neuroinflammation mediated by Aβ₁₋₄₂ in BV-2 cells.

Inflammation is an important contributor to the development of Alzheimer's disease (AD). Anti-inflammatory medication may offer promising treatment for AD. Hydroxy-safflor yellow A (HSYA), a chemical component of the safflower yellow pigments, has been reported to exert potent immunosuppressive effects. This study examined the anti-inflammatory effects of HSYA in Aβ₁₋₄₂-treated BV-2 microglia cells. The mRNA levels of IL-1β, IL-4, IL-10, TNF-α, COX-2 and iNOS were detected by real-time PCR. Western blotting was used to determine the protein expression of COX-2, TNF-α, iNOS, Janus Kinase 2 (JAK2), p-JAK2, signal transducers and activators of transcription 3 (STAT3) and p-STAT3. BV2-conditioned medium was used to treat SH-SY5Y cells and primary neuronal cells in indirect toxicity experiments. Cell viability and apoptosis were assessed using MTT assay and Annexin V/PI staining respectively. The results demonstrated that HSYA significantly reduced the expression of the pro-inflammatory mediators and inhibited Aβ₁₋₄₂-induced neuroinflammation. Moreover, HSYA protected primary cortical neurons and SH-SY5Y cells against microglia-mediated neurotoxicity. HSYA also enhanced the phosphorylation of JAK2/STAT3 pathway and inhibition of JAK2 by AG 490 attenuated the anti-inflammatory effects of HSYA. Overall, our findings suggested that HSYA inhibited Aβ₁₋₄₂-induced inflammation and conferred neuroprotection partially through JAK2/STAT3 pathway, indicating that HSYA could be a potential drug for the treatment of AD.