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

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.