Structure characteristics of a polysaccharide isolated from safflower and its neuroprotective effects against cerebral ischemia/reperfusion injury by LASSO regression analysis of transcriptomic and metabolomic data.

Multi-omics allows for the systematic analysis of molecular information for each biological layer, while also posing the challenge of extracting valuable insights from exponentially growing multi-omics data. Here, we present a roadmap for multi-omics integrated analysis using a least absolute shrinkage and selection operator (LASSO) strategy. In this study, one novel purified safflower polysaccharide (SP1) was successfully obtained. The main chain of the polysaccharide was →4)-α-D-GalpA. Infarct size measurements and histopathology analysis results revealed the significant neuroprotective effects of SP1 in rats with middle cerebral artery occlusion/reperfusion (MCAO/R). Combined transcriptomic and metabolomic analyses identified 341 differentially expressed genes and 317 metabolites altered by SP1 treatment. Ultimately, the Galnt15 gene associated with the neuroprotective effect of SP1 was further identified using the LASSO regression approach. Mechanistically, SP1 upregulated PI3K, AKT, and p-AKT, while downregulating TNF-α, NF-κB p65, p38, and p-p38, indicating that SP1 suppressed inflammation via the p38 MAPK and PI3K/AKT pathways. Molecular docking and dynamics simulation confirmed the high affinity and stability between SP1 and Galnt15. Our study provides a novel strategy to decipher the neuroprotective mechanism of SP1, which may become an effective treatment for ischemic stroke.