School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Clinical Pharmacy of The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, China; School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Int J Biol Macromol. 2022 Jan 1;194:546-555. doi: 10.1016/j.ijbiomac.2021.11.097. Epub 2021 Nov 19.
PTP70-2, a novel polysaccharide isolated from Polygala tenuifolia in our previous publication, exhibits potential anti-inflammatory effects. Here, we investigate the mechanisms underlying these effects and the neuroprotective activity of PTP70-2 in lipopolysaccharide (LPS)-damaged BV2 microglial cells and neuroinflammation-injured primary cortical neurons. The results suggest that PTP70-2 dramatically reduces the LPS-stimulated inflammatory cytokines overexpression, as well as down-regulates the levels of TLR4-, MyD88-, and NF-κB-related proteins. The effect of PTP70-2 in down-regulation of proinflammatory cytokines and downstream proteins implicated in MyD88 and NF-κB signaling is related to the TLR4 pathway. Furthermore, this effect is enhanced by the co-incubation of BV2 cells with PTP70-2 and TAK242, a TLR4 inhibitor, before exposure to LPS. Importantly, PTP70-2 prevents neuroinflammation-induced neurotoxicity by mitigating ROS overproduction and MMP dissipation. Overall, the PTP70-2's anti-neuroinflammation and neuroprotection are involved to the modulation of the TLR4-mediated MyD88/NF-κB signaling pathway.
PTP70-2 是我们之前的出版物中从远志中分离得到的一种新型多糖，具有潜在的抗炎作用。在这里，我们研究了 PTP70-2 在脂多糖 (LPS) 损伤的 BV2 小胶质细胞和神经炎症损伤的原代皮质神经元中的作用机制及其神经保护活性。结果表明，PTP70-2 可显著降低 LPS 刺激的炎症细胞因子过表达，并下调 TLR4、MyD88 和 NF-κB 相关蛋白的水平。PTP70-2 下调与 MyD88 和 NF-κB 信号转导有关的炎症细胞因子和下游蛋白的作用与 TLR4 途径有关。此外，在 LPS 暴露前，将 PTP70-2 与 TLR4 抑制剂 TAK242 共同孵育 BV2 细胞，可增强这种作用。重要的是，PTP70-2 通过减轻 ROS 过度产生和 MMP 耗散来防止神经炎症引起的神经毒性。总之，PTP70-2 的抗神经炎症和神经保护作用涉及 TLR4 介导的 MyD88/NF-κB 信号通路的调节。
