Tanshinone IIA (tan IIA), a key component of Salvia miltiorrhiza Bunge (Danshen), has been proven to play a significant role in suppressing inflammation. However, the molecular mechanisms underlying the anti-inflammatory properties of tan IIA against lipopolysaccharide (LPS)-induced neuroinflammation and neurotoxicity in human U87 astrocytoma cells have not been well justified. Therefore, in this study, U87 cells were pretreated with tan IIA (1, 5 and 10 μM) for 30 min, followed by stimulation with LPS for 24 h. Immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blotting were performed to investigate the effects of tan IIA on neuroinflammatory responses. The findings demonstrated that tan IIA prevented LPS-induced cell viability decrease, inhibited U87 cells activation, and suppressed the expression of glial fibrillary acidic protein (GFAP). Furthermore, tan IIA significantly reduced the mRNA expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in LPS-stimulated U87 cells. Meanwhile, the increased protein levels of IL-1β, TNF-α, and IL-6 in cell culture supernatants were also markedly inhibited by tan IIA. Moreover, tan IIA significantly alleviated the phosphorylation of IκBα, nuclear factor-kappa B (NF-κB), p38, and JNK induced by LPS. Additionally, tan IIA suppressed the upstream signaling adaptor molecules toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), and tumor necrosis factor receptor-associated factor 6 (TRAF6). Blockade of NF-κB, p38, and JNK obviously attenuated IL-1β, TNF-α, and IL-6 in U87 cells. In conclusion, the present results suggested that tan IIA can attenuate LPS-induced neurotoxicity and neuroinflammation partly by inhibiting TLR4/NF-κB/MAPKs signaling pathways in U87 cells.

丹参酮 IIA (tan IIA)，丹参的关键成分Bunge（丹参）已被证明在抑制炎症方面发挥着重要作用。然而，tan IIA 对抗脂多糖 (LPS) 诱导的人类 U87 星形细胞瘤细胞中的神经炎症和神经毒性的抗炎特性的分子机制尚未得到充分证明。因此，在本研究中，U87 细胞用棕褐色 IIA（1、5 和 10 μM）预处理 30 分钟，然后用 LPS 刺激 24 小时。进行免疫荧光、逆转录聚合酶链反应 (RT-PCR)、酶联免疫吸附测定 (ELISA) 和蛋白质印迹法以研究 tan IIA 对神经炎症反应的影响。研究结果表明，tan IIA 可防止 LPS 诱导的细胞活力降低，抑制 U87 细胞活化，并抑制胶质纤维酸性蛋白（GFAP）的表达。此外，tan IIA 显着降低了 LPS 刺激的 U87 细胞中白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α) 和白介素-6 (IL-6) 的 mRNA 表达。同时，细胞培养上清液中 IL-1β、TNF-α 和 IL-6 蛋白水平的升高也受到 tan IIA 的显着抑制。此外，tan IIA 显着减轻 LPS 诱导的 IκBα、核因子-κB (NF-κB)、p38 和 JNK 的磷酸化。此外，tan IIA 抑制上游信号转导分子 toll 样受体 4 (TLR4)、骨髓分化初级反应蛋白 88 (MyD88) 和肿瘤坏死因子受体相关因子 6 (TRAF6)。NF-κB、p38 和 JNK 的阻断明显减弱了 U87 细胞中的 IL-1β、TNF-α 和 IL-6。综上所述，