Potential roles of HSYA in attenuating sepsis-induced liver injury through multi-omics analysis

Liver injury is a strong independent predictor of mortality in patients with sepsis, in which gut dysbiosis plays a crucial role. Hydroxyl safflower yellow A (HSYA), an important component of safflower, has been used to treat liver injury in animal models. However, its role in sepsis-induced liver dysfunction and the specific molecular mechanisms remain unclear. In the current study, we first discussed the discrepancy in the gut microbiota between the cecal ligation puncture (CLP) and HSYA groups using 16 S RNA sequencing. Our data demonstrated that HSYA supplementation significantly decreased the relative abundance of Proteobacteria, Firmicutes, and Campylobacterota, and further decreased the abundance of Bacteroidota, suggesting that the protective effects of HSYA against sepsis-induced liver injury may be partially attributed to the alteration of these bacteria. In addition, the metabolomic data identified 823 differentially expressed metabolites associated with sepsisinduced liver injury. After HSYA supplementation, the levels of 56 metabolites were restored to sham-like levels. Transcriptomic analysis revealed 4990 differentially expressed genes (DEGs) between the sham and CLP groups, and after HSYA injection, 1613 genes were modulated. Comprehensive analysis demonstrated that the enrichment pathways of the 903 DEGs mainly focused on inflammatory responses, amino acid metabolism, and Lipid reactions. In conclusion, our study revealed the potential mechanism of action of HSYA in sepsisinduced liver injury through a comprehensive analysis of 16 S RNA sequencing, metabolomics, and transcriptomics, thus providing a theoretical basis for further clinical applications of HSYA.