Alisma plantago-aquatica polysaccharides ameliorate acetaminophen-induced acute liver injury by regulating hepatic metabolic profiles and modulating gut microbiota.

Acetaminophen (APAP) has emerged as a predominant contributor to acute liver failure (ALF) in United States. Alismatis rhizoma, a commonly used traditional herbal medicine, contains small molecular components with extensive hepatoprotective activity. However, the specific role of Alismatis rhizoma polysaccharide (ARP) in liver protection remains unclear. ARP50 and ARP70, derived through graded alcohol precipitation and refinement, predominantly consisted of varying proportions of glucose, galactose, and arabinose. In vitro experiments on free radical scavenging demonstrated notable antioxidant capabilities of ARP50 and ARP70. To investigate the hepatoprotective effects, an APAP-induced acute liver injury (ALI) model was established in mice. ARP50 and ARP70 exerted dose-dependent therapeutic effects on APAP-induced liver injury. Further analysis of liver metabolites revealed that ARPs facilitated the reconstruction of the liver antioxidant system by modulating the metabolism network centered on l-glutamine. In addition, the abundance of gut microbiota was altered under the influence of ARPs. ARP50 significantly reduced the levels of Pseudarthrobacter and markedly increased the levels of Faecalibacterium，At the same time, ARP50 could increase the levels of acetic acid in the liver and serum. Meanwhile, ARP70 significantly increased the abundance of Dubosiella, Muribaculum, Ileibacterium, and Prevotellaceae UCG 001, while reducing the abundance of Escherichia Shigella and Pseudarthrobacter. The results indicated that ARPs could exert a protective effect against APAP-induced acute liver injury by reshaping the liver metabolic profile and modulating the gut microbiota.