PDF(Pubmed)
Abstract：
Naturally occurring homoisoflavonoids isolated from some Liliaceae plants have been reported to have diverse biological activities (e.g., antioxidant, anti-inflammatory, and anti-angiogenic effects). The exact mechanism by which homoisoflavonones exert anti-neuroinflammatory effects against activated microglia-induced inflammatory cascades has not been well studied. Here, we aimed to explore the mechanism of homoisoflavonoid SH66 having a potential anti-inflammatory effect in lipopolysaccharide (LPS)-primed BV2 murine microglial cells. Microglia cells were pre-treated with SH66 followed by LPS (100 ng/mL) activation. SH66 treatment attenuated the production of inflammatory mediators, including nitric oxide and proinflammatory cytokines, by down-regulating mitogen-activated protein kinase signaling in LPS-activated microglia. The SH66-mediated inhibition of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex and the respective inflammatory biomarker-like active interleukin (IL)-1β were noted to be one of the key pathways of the anti-inflammatory effect. In addition, SH66 increased the neurite length in the N2a neuronal cell and the level of nerve growth factor in the C6 astrocyte cell. Our results demonstrated the anti-neuroinflammatory effect of SH66 against LPS-activated microglia-mediated inflammatory events by down-regulating the NLRP3 inflammasome complex, with respect to its neuroprotective effect. SH66 could be an interesting candidate for further research and development regarding prophylactics and therapeutics for inflammation-mediated neurological complications.
摘要：
据报道，从某些百合科植物中分离出的天然存在的高异黄酮类化合物具有多种生物活性（例如，抗氧化剂，抗炎,和抗血管生成作用)。高异黄酮对活化的小胶质细胞诱导的炎症级联反应发挥抗神经炎作用的确切机制尚未得到很好的研究。这里,我们旨在探讨高异黄酮类SH66在脂多糖（LPS）引发的BV2鼠小胶质细胞中具有潜在抗炎作用的机制。用SH66预处理小胶质细胞,随后用LPS(100ng/mL)活化。SH66治疗减轻了炎症介质的产生，包括一氧化氮和促炎细胞因子,通过下调LPS激活的小胶质细胞中的丝裂原激活的蛋白激酶信号传导。SH66介导的核苷酸结合寡聚化结构域样受体家族pyrin结构域包含3（NLRP3）炎性体复合物和相应的炎症生物标志物样活性白介素（IL）-1β的抑制被认为是抗炎作用的关键途径之一。此外,SH66增加了N2a神经元细胞中的神经突长度和C6星形胶质细胞中的神经生长因子水平。我们的结果表明，SH66通过下调NLRP3炎性体复合物，对LPS激活的小胶质细胞介导的炎症事件具有抗神经炎症作用。关于它的神经保护作用。SH66可能是有关炎症介导的神经系统并发症的预防和治疗的进一步研究和开发的有趣候选者。
