Epigoitrin ameliorates acute liver injury in mice via regulation of the TLR4/NF-κB signaling pathway

Background Acute liver injury (ALI), frequently triggered by drugs, toxins, or viral infections, is closely associated with the aberrant activation of the TLR4/NF-κB signaling pathway. Epigoitrin (EPG), a major bioactive component derived from Isatis indigotica root, exhibits anti-inflammatory, antioxidant properties, and potential NF-κB inhibitory effects. However, the specific mechanisms underlying its therapeutic action in ALI remain to be elucidated. Objective To investigate the protective effects and underlying mechanisms of EPG against carbon tetrachloride (CCl ₄ )-induced ALI in mice. Methods Kunming mice were randomly divided into five groups: normal control group, model group, bifendate group, high-dose EPG group, and low-dose EPG group. The treatment groups received corresponding doses of the drugs, while the normal control and model groups were given an equal volume of distilled water via intragastric gavage once daily for 7 consecutive days. One hour after the final administration, all groups except the normal control group were intraperitoneally injected with 0.2% CCl₄-olive oil solution to induce liver injury. Sixteen hours post-injection, blood samples were collected to measure serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissues were harvested to assess interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was performed to observe histopathological changes in the liver. The effects on the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway were evaluated by quantitative real-time PCR and Western blot analysis. Results EPG significantly reduced serum liver function markers (ALT and AST) and levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in mice ( P <0.05). Histopathological examination demonstrated that EPG effectively ameliorated CCl₄-induced hepatocellular necrosis. Furthermore, qPCR and Western blot (WB) analyses revealed that EPG markedly suppressed the TLR4/NF-κB signaling pathway ( P <0.05). Conclusion EPG exerts a protective effect against CCl₄-induced ALI in mice, and its mechanism may involve the suppression of the TLR4/NF-κB signaling pathway.