Xiaobugan decoction prevents CCl-induced acute liver injury by modulating gut microbiota and hepatic metabolism.

BACKGROUND

The liver plays a crucial role in detoxification and metabolism. When its capacity to metabolize foreign substances is exceeded, it can lead to acute liver injury (ALI). Therefore, preventing liver disease and maintaining daily liver health are of utmost importance. Xiaobugan Decoction (XBGD), a traditional Chinese medicine (TCM) formula, is recorded in 'Fuxingjue', is used in folk practice to promote liver health and regulate respiration. However, the hepatoprotective mechanisms of XBGD remained unclear.

PURPOSE

We investigated the prophylactic and hepatoprotective effects of XBGD and explored its related molecular mechanisms using a mouse model of carbon tetrachloride (CCl)-induced ALI.

STUDY DESIGN AND METHODS

XBGD composition was determined using analytical methods, and the main compounds were identified using ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) and high-performance liquid chromatography (HPLC). A CCl-induced L02 cell injury model was employed to explore the protective effects of XBGD on liver cells, and a CCl-induced ALI mouse model was used to investigate the hepatoprotective effects of XBGD.

RESULTS

Cellular experiments demonstrated that XBGD had a protective function against L02 cell damage by increasing cell viability, restoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD) levels, reducing malondialdehyde (MDA) content, and improving mitochondrial membrane potential (ΔΨm). In the mouse ALI model, XBGD prevented ALI by reducing ALT, AST, and alkaline phosphatase (ALP) levels and inhibiting oxidative stress. Quantitative real-time polymerase chain reaction (qPCR), immumohistochemical staining and western blotting results revealed that XBGD exerted hepatoprotective effects by reducing inflammatory responses and inhibiting cell apoptosis. Furthermore, H-NMR metabolomics indicated that XBGD regulates hepatic and intestinal metabolism, whereas 16S rDNA sequencing demonstrated the regulatory effects of XBGD on the gut microbiota. Correlation analysis highlighted the close relationship among gut microbiota, metabolites, and ALI indicators.

CONCLUSIONS

XBGD is a promising TCM for the prevention of CCl-induced ALI via regulation of microbiota and metabolism. This study provides a new perspective on the development of hepatoprotective measures and the prevention of liver disease in daily life.