Integrative multi-omics reveals that salvianolic acid a protects against septic liver injury by remodeling amino acid metabolism and redox homeostasis.
TL;DR
Sal A protects against SILI through coordinated regulation of amino acid metabolism, redox homeostasis, apoptosis, immune responses, and inflammatory signaling pathways, and the lack of direct mechanistic validation of key molecular targets.
Abstract
Background
Sepsis-induced liver injury (SILI) is a severe complication of sepsis associated with high morbidity and mortality. Salvianolic acid A (Sal A), a bioactive phenolic compound isolated from Salvia miltiorrhiza Bunge, exhibits hepatoprotective properties. However, its effects against SILI and underlying molecular mechanisms remain unclear.
Methods
A cecal ligation and puncture (CLP)-induced murine sepsis model was established to evaluate the hepatoprotective effects of Sal A. Liver injury was assessed by serum biochemical assays and histopathological examination. Integrated transcriptomic, proteomic, and metabolomic analyses were performed to investigate the molecular mechanisms of Sal A-mediated hepatoprotection.
Results
Sal A significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated hepatic histopathological injury in septic mice. Multi-omics analyses identified 236 differentially expressed genes (DEGs), 590 differentially expressed proteins (DEPs), and 370 differentially expressed metabolites (DEMs). Integrated analyses revealed that Sal A mainly regulated amino acid metabolism, oxidative stress, apoptosis, immune responses, and inflammatory signaling pathways, identifying key regulatory molecules and 37 shared metabolic pathways.
Conclusions
Sal A protects against SILI through coordinated regulation of amino acid metabolism, redox homeostasis, apoptosis, immune responses, and inflammatory signaling pathways. Nevertheless, this study has several limitations, including the use of a CLP-induced mouse model, the preventive administration strategy rather than post-onset treatment, and the lack of direct mechanistic validation of key molecular targets. Further studies using clinically relevant therapeutic protocols and targeted experiments are required to confirm the translational potential of Sal A.