Department of Emergency Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong New Area, Shanghai 200137, China.
General Practice Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Pudong New Area, Shanghai 200137, China.
Int Immunopharmacol. 2023 Apr;117:109975. doi: 10.1016/j.intimp.2023.109975. Epub 2023 Mar 20.
Salidroside (SAL) is a natural bioactive compound with anti-oxidative, anti-inflammatory, and neuroprotective properties. In the present study, we generate an experimental design to investigate SAL-mediated protective effect and underlying mechanism on lipopolysaccharide (LPS)-induced neuroinflammation and cognitive impairment in the septic encephalopathy mice model (SEMM). In SEMM, Open-Field Test (OFT) and Novel Object Recognition Test evaluated LPS-induced cognitive impairment, behavioural phenotypes, and memory impairment (NOR). Cytokines and protein expression were assessed using ELISA assay, RT-qPCR, and Western blotting. Our results showed cognitive dysfunction could be reversed when treated with SAL in SEMM. SAL treatment significantly reduced apoptotic TUNEL-positive cells and related gene expression (BAX and BCL-2) and considerably improved neuronal damage in SEMM. In addition, it markedly reduced the production of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and Iba-1-positive cells responsible for microglial activation in mice hippocampus (P < 0.05). The effects of SAL on ROS and oxidative stress markedly reduced malondialdehyde (MDA) content and increased superoxide dismutase (SOD) and catalase (CAT) in the hippocampal tissues of mice. Besides, SAL treatment enhanced LPS-induced autophagy in mice's hippocampus and increased autophagy-related protein expression (Beclin-1 and P62). In addition, the NLRP3 inflammasome pathway and its related proteins (NLRP3, ASC, and cleaved caspase-1) were suppressed by SAL treatment. However, SAL activated the SIRT1/Nrf2 pathway and exerts protection by enhanced expression of the proteins (SIRT1 and Nrf2) and downstream genes (HO-1 and NQO1). Our finding demonstrated that SAL employed neuroprotective effects in SEMM by promoting autophagy via activation of the SIRT1 pathway.
红景天苷（SAL）是一种具有抗氧化、抗炎和神经保护作用的天然生物活性化合物。在本研究中，我们设计了一个实验来研究 SAL 对脂多糖（LPS）诱导的脓毒症脑病小鼠模型（SEMM）中神经炎症和认知障碍的保护作用及其潜在机制。在 SEMM 中，旷场试验（OFT）和新物体识别试验评估 LPS 诱导的认知障碍、行为表型和记忆障碍（NOR）。使用 ELISA 测定、RT-qPCR 和 Western blot 测定评估细胞因子和蛋白质表达。我们的结果表明，在 SEMM 中，SAL 治疗可逆转认知功能障碍。SAL 治疗显著减少凋亡 TUNEL 阳性细胞和相关基因表达（BAX 和 BCL-2），并显著改善 SEMM 中的神经元损伤。此外，它显著降低了炎性细胞因子（TNF-α、IL-1β 和 IL-6）和负责小胶质细胞活化的 Iba-1 阳性细胞的产生（P<0.05）。SAL 对 ROS 和氧化应激的作用显著降低了小鼠海马组织中丙二醛（MDA）的含量，增加了超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的含量。此外，SAL 治疗增强了 LPS 诱导的小鼠海马自噬，并增加了自噬相关蛋白表达（Beclin-1 和 P62）。此外，SAL 治疗抑制了 NLRP3 炎性小体途径及其相关蛋白（NLRP3、ASC 和切割的半胱天冬酶-1）的表达。然而，SAL 通过激活 SIRT1 通路增强自噬，增强了 SIRT1/Nrf2 通路的表达，增强了蛋白质（SIRT1 和 Nrf2）和下游基因（HO-1 和 NQO1）的表达。我们的研究结果表明，SAL 通过激活 SIRT1 通路促进自噬，从而发挥对 SEMM 的神经保护作用。
