Structural characterization and multi-omics analysis of novel Saposhnikovia divaricata (Turcz.) Schischk acidic heteropolysaccharide alleviating acute liver injury.

Abstract

BACKGROUND: Acute liver injury (ALI) can result from multiple etiological factors, including drug toxicity and viral infection. Notably, drug-induced ALI is primarily mediated through oxidative stress, inflammatory responses, and gut microbiota dysbiosis. Although Saposhnikovia divaricata polysaccharides exhibit promising hepatoprotective potential, the underlying mechanisms-particularly those involving the gut-liver axis and metabolic regulation-remain poorly understood. PURPOSE: This study aims to isolate and structurally characterize a novel acidic heteropolysaccharide, SD-1, from S. divaricata, and to investigate its protective mechanisms against APAP-induced acute liver injury, with particular emphasis on its regulatory effects on gut microbiota and metabolic pathways. METHODS: SD-1 was isolated and characterized. Its efficacy was assessed in an APAP-injured mouse model using histopathology, serum biochemistry, Western blot, metabolomics, and 16S rRNA sequencing. RESULTS: SD-1 treatment alleviated hepatic necrosis and reduced ALT/AST levels. It activated the Nrf2/HO-1 pathway to reduce oxidative stress and inhibited the TLR4/NF-κB cascade to suppress inflammation. SD-1 also downregulated pro-inflammatory arachidonic acid metabolism and restored gut microbiota balance by increasing Akkermansia and decreasing Escherichia-Shigella. CONCLUSION: The novel polysaccharide SD-1 alleviates APAP-ALI via multi-target mechanisms, including direct antioxidant/anti-inflammatory effects, suppression of arachidonic acid metabolism, and gut-liver axis modulation, highlighting its therapeutic potential.