Edgeworthia gardneri (Wall.) Meisn Mitigates CCL4-induced liver injury in mice by modulating gut microbiota, boosting antioxidant defense, and reducing inflammation

Herbal medicine has become an area of growing global scientific interest. The prime objective of this study was to investigate the protective role of Edgeworthia gardneri (Wall.) Meisn (EGM polysaccharide) against carbon tetrachloride (CCl₄)-induced liver injury in mice. Forty-five ICR mice were randomly divided into three groups (n = 15): IC, IM, and IT. The IT group received EGM polysaccharide solution (50 mg/kg) daily, while the IC and IM groups were administered an equivalent volume of normal saline. The IT and IM groups were intraperitoneally injected with a mixture of CCl₄ and olive oil at 1:1 (v/v) (2 mL/kg) every 3 days. Our results showed that EGM polysaccharide significantly (p < 0.05) reduced pathological hepatic alterations and an increased liver index caused by CCl₄. Moreover, EGM polysaccharide therapy significantly (p < 0.001) increased levels of antioxidant enzymes, such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) and reduced malondialdehyde (MDA) content in a dose-dependent manner. Notably, EGM polysaccharide alleviated the inflammatory cascades as evidenced by decreased serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor- α (TNF-α) under CCl₄ administration. Furthermore, 16 s rRNA gene sequencing results exhibited that EGM polysaccharide increased the abundance of probiotics bacteria, such as Unclassified_Lachnospiraceae, and decreased the abundance of pathogenic bacterial texas like Brevundimonas and Candidatus_Nitrocosmicu. Conclusively, EGM polysaccharide protects against CCl₄-induced oxidative stress and inflammation in the liver and alleviates hepatic injury through beneficial gut microbiota modulations. The current study suggests that EGM polysaccharide is an effective agent in counteracting CCl₄-induced hepatic damage.