Echinacoside mitigates sepsis-associated encephalopathy by inhibiting STING pathway and reducing neuroinflammation

Sepsis-associated encephalopathy (SAE) is a prevalent and severe complication in septic patients, characterized by diffuse brain dysfunction and high mortality rates. Current treatment options are limited, necessitating the exploration of novel therapeutic approaches. Echinacoside (ECH) has demonstrated neuroprotective effects in various neurodegenerative models. This study investigates the neuroprotective potential of ECH on SAE and elucidates the underlying mechanism.

A sepsis model was established using male C57BL/6 mice (8-10 weeks old) via cecum ligation and puncture (CLP). Cognitive impairment was assessed by open field test (OFT), sucrose preference test (SPT), elevated plus maze test (EPM), and Barnes maze test (BMT). Mitochondrial ultrastructure in the cortex was observed by Transmission electron microscopy. mRNA and protein expression levels were measured by RT-qPCR, Western blot, and immunohistochemical staining.

ECH administration significantly alleviated cognitive impairment in septic mice, meanwhile, dysfunction of microglial mitochondria, release of reactive oxygen species, activation of cGAS/stimulator of interferon genes (STING) signaling pathway has been found reversed after the ECH treatment. Furthermore, increase the release of ROS can significantly rescued the neuroprotective effect of ECH on septic mice.

These findings suggest that ECH exerts its neuroprotective effects by targeting the cGAS-STING pathway, offering a promising therapeutic strategy for SAE.