Hydroxysafflor Yellow A Inhibits Aβ1–42-Induced Neuroinflammation by Modulating the Phenotypic Transformation of Microglia via TREM2/TLR4/NF-κB Pathway in BV-2 Cells

• DOI: 10.1007/s11064-021-03484-x
• Publication Date: 2021-11-16T06:04:17Z
• Authors: Mengqiao Ren; Mengyu Zhang; Xiaoyan Zhang; Chunhui Wang; Yanjie Zheng; Yanli Hu
• Keywords: 0301 basic medicine; 0303 health sciences; Amyloid beta-Peptides; Membrane Glycoproteins; NF-kappa B; Quinones; Peptide Fragments; 3. Good health; Toll-Like Receptor 4; Mice; 03 medical and health sciences; Chalcone; Phenotype; Neuroinflammatory Diseases; Animals; Microglia; Receptors, Immunologic; Signal Transduction

Hydroxysafflor yellow A (HSYA) is an extract from Carthamus tinctorius L. dry flowers (Compositae). HSYA has been shown to have neuroprotective effects on several Alzheimer's disease (AD) models. However, the exact mechanisms by which HSYA regulates neuroinflammation have still not been clarified. In this study, we investigated the mechanism by which HSYA regulates microglial 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 viability and improve the morphology of BV-2 cells injured by Aβ1-42. The results showed that Aβ1-42 could induce microglia to upregulate the expression of M1 markers (iNOS, IL-1β, IL-6) and downregulate M2 marker (Arg-1, IL-4, IL-10, IL-13) expression. HSYA reversed the effects of Aβ1-42 via TREM2, switching microglia from an M1 proinflammatory phenotype to an M2 anti-inflammatory phenotype. HSYA inhibited the Aβ1-42-induced activation of the TLR4/NF-κB transduction pathway by upregulating TREM2 and regulated the transcription of inflammatory cytokines via the downstream transcription factors NF-κB p65 and IκB-α. In conclusion, HSYA regulated the microglial inflammatory phenotype by regulating microglial (M1/M2) polarization in Aβ1-42-induced BV-2 cells which may be mediated by the TREM2/TLR4/NF-κB pathway.