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
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
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DOI：
10.1007/s11064-021-03484-x
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发表时间：
2021-11-16
影响因子：
4.4
通讯作者：
Hu, Yanli
中科院分区：
文献类型：
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作者：
Ren, Mengqiao;Zhang, Mengyu;Hu, Yanli
羟基红花黄色素A（HSYA）是红花的提取物。干燥的花（菊科）。HSYA已被证明对几种阿尔茨海默病（AD）模型具有神经保护作用。然而，HSYA调节神经炎症的确切机制仍不清楚。在本研究中，我们研究了HSYA通过TREM 2调节小胶质细胞活化和神经炎症的机制，并进一步阐明了其潜在的分子机制。我们沉默BV-2细胞中的TREM 2并评估炎症标志物（TNF-α、IL-1 β、IL-4、IL-6、IL-10和IL-13）的表达。结果表明，HSYA能上调A β（1-42）损伤的BV-2细胞活力，改善细胞形态。结果表明，A β（1-42）可诱导小胶质细胞M1标志物（iNOS、IL-1 β、IL-6）表达上调，M2标志物（Arg-1、IL-4、IL-10、IL-13）表达下调。HSYA通过TREM 2逆转A β（1-42）的作用，将小胶质细胞从M1促炎表型转换为M2抗炎表型。HSYA通过上调TREM 2抑制A β（1-42）诱导的TLR 4/NF-κ B转导通路的激活，并通过下游转录因子NF-κ B p65和I κ B-α调节炎性细胞因子的转录。总之，HSYA通过调节A β（1-42）诱导的BV-2细胞中小胶质细胞（M1/M2）极化来调节小胶质细胞炎症表型，这可能是由TREM 2/TLR 4/NF-κ B途径介导的。
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-alpha, IL-1 beta, 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 A beta(1-42). The results showed that A beta(1-42) could induce microglia to upregulate the expression of M1 markers (iNOS, IL-1 beta, IL-6) and downregulate M2 marker (Arg-1, IL-4, IL-10, IL-13) expression. HSYA reversed the effects of A beta(1-42) via TREM2, switching microglia from an M1 proinflammatory phenotype to an M2 anti-inflammatory phenotype. HSYA inhibited the A beta(1-42)-induced activation of the TLR4/NF-kappa B transduction pathway by upregulating TREM2 and regulated the transcription of inflammatory cytokines via the downstream transcription factors NF-kappa B p65 and I kappa B-alpha. In conclusion, HSYA regulated the microglial inflammatory phenotype by regulating microglial (M1/M2) polarization in A beta(1-42)-induced BV-2 cells which may be mediated by the TREM2/TLR4/NF-kappa B pathway.