HSYA inhibits Aβ1-42 -induced neuroinflammation by promoting microglial M2 polarization via TREM2/TLR4/NF- κB pathway in BV-2 cells.

Abstract Hydroxysafflor yellow A (HSYA), an extract from Carthamus tinctorius L. Dry flowers (Compositae). HSYA has been shown to have neuroprotective effects in several AD models. However, the exact mechanisms of HSYA regulate neuroinflammation have still not been clarified. In this study, we investigated the mechanism by which HSYA regulates microglia activation and neuroinflammation via TREM2, and further clarified its underlying molecular mechanism. We silenced TREM2 in BV-2 cells and evaluated the expression of inflammatory markers (TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-13). The results showed that HSYA could up-regulate cell activity and improve the morphology of BV-2 cells injured by Aβ1−42. HSYA up-regulated expression of M1 markers (iNOS, IL-1β, IL-6) and down-regulated expression of M2 markers (Arg-1, IL-4, IL-10, IL-13) by TREM2, and changed microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. HSYA inhibited the activation of TLR4/ NF-κB transduction pathway induced by Aβ1−42 by up-regulating TREM2, and regulated the transcription of inflammatory cytokines by downstream transcription factors NF-κB p65 and IκB-α. In conclusion, HSYA regulated microglial inflammatory phenotype by regulating microglial (M1/M2) polarization in Aβ1−42-induced BV-2 cells which may be mediated through TREM2/TLR4/NF-κB pathway.