OBJECTIVE To explore the protective effect and molecular mechanism of Ilex pubescens triterpenoid saponins(IPTS) on acute liver injury induced by lipopolysaccharide(LPS) in mice based on transcriptomics.

METHODS Thirty-six 6−8-week-old male C57BL/6 mice were randomly divided into normal group, model group, silymarin positive control group(50 mg·kg⁻¹), and low-, medium-, high-dose IPTS groups(30, 60, and 120 mg·kg⁻¹), with 6 mice in each group. An acute liver injury model was established by intraperitoneal injection of LPS(10 mg·kg⁻¹). Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of liver tissues. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), myeloperoxidase(MPO), inducible nitric oxide synthase(iNOS), superoxide dismutase(SOD), and inflammatory factors(TNF-α, IL-10, IL-1β) in serum were detected by ELISA. The potential mechanism of IPTS was explored by combining transcriptome sequencing technology.

RESULTS Compared with the model group, the liver histopathological damage in the IPTS treatment groups was significantly improved, characterized by regular arrangement of hepatocytes and reduced infiltration of inflammatory cells. The levels of serum ALT and AST were significantly decreased(P<0.001), and the levels of oxidative stress indicators(MPO, iNOS, SOD) and inflammatory factors(TNF-α, IL-1β, IL-6) were significantly improved(P<0.001). Transcriptome analysis showed that a total of 115 differentially expressed genes were identified in the high-dose IPTS group, which were mainly enriched in pathways closely related to oxidative stress and inflammation, such as arachidonic acid metabolism, TRP channel inflammatory regulation, and B-cell receptor signaling.

CONCLUSION IPTS can ameliorate LPS-induced acute liver injury in mice by suppressing the release of inflammatory factors, balancing oxidative stress levels, and modulating the C₂H₂ zinc finger protein and TRAF transcription factor network, thereby protecting the liver through regulation of lipid metabolism, intestinal immunity, and TRP channel-mediated inflammatory pathways.