Salidroside attenuates lipopolysaccharide-induced neuroinflammation and cognitive impairment in septic encephalopathy mice

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.

Autophagy; Cognitive impairment; Lipopolysaccharide; Neuroinflammation; Salidroside.