Lycium Barbarum Glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs/NF-kB and pyroptosis pathways.

Abstract Background Lycium barbarum polysaccharides (LBP) is an activity ingredient extracted from Lycium barbarum, which has the effect of inhibiting neuroinflammation. Lycium Barbarum Glycopeptide (LbGp) is a glycoprotein with immunological activity that is further purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action is still unclear. Aims In this study, we aim to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. Methods SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally, and the spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated by metabolomics and molecular biology techniques such as western blot, q-PCR. Results Through in vivo and in vitro experiments, it was found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, it was found that LbGp can induce the secretion of docosahexaenoic acid (DHA) by microglia, and DHA can inhibit neuroinflammation through the MAPKs/NF-kB and pyroptosis pathways. Conclusions In summary, we believe that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA in microglia, thereby inhibiting the MAPKs/NF-kB and pyroptosis pathways, promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.