Sea cucumber sulfated fucan protects against acute liver injury in mice: insights from inflammatory responses, gut microbiota and hepatic metabolic profile analyses

Abstract

As a natural polysaccharide, sulfated fucan from sea cucumber possesses multiple biological activities, but its protective effect on acute liver injury (ALI) is still unclear. The aim of this study was to clarify the protective effects of sulfated fucan from sea cucumber on lipopolysaccharide (LPS)-induced ALI in mice. After administering sulfated fucan from sea cucumber (100 mg kg⁻¹ d⁻¹) to mice via gavage for 14 days, an ALI model was induced by intraperitoneal injection of LPS. The results showed that pretreatment with sulfated fucan from sea cucumber significantly reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels, alleviated histopathological liver damage, suppressed the expression of pro-inflammatory factors (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), elevated the anti-inflammatory factor level (IL-10), and enhanced the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)). Additionally, FUC suppressed the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway and activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathway gene expression. 16S rRNA sequencing indicated that sulfated fucan from sea cucumber mainly increased the proportions of Lachnospiraceae_NK4A136_group and Christensenellaceae_R-7_group. Liver metabolomics analysis revealed that FUC reversed LPS-induced disturbances in purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study demonstrates that sulfated fucan from sea cucumber exerts hepatoprotective effects by modulating the “gut–liver axis”, providing a scientific basis for its use as a functional food or dietary supplement in the prevention of ALI.