Abstract
BACKGROUND: Current treatments for cirrhosis-a progressive disease marked by fibrosis and inflammation-are limited and non-specific. Jinqiancao granules (JQC), a traditional Chinese medicine used for hepatobiliary diseases, could provide a promising new therapeutic approach. PURPOSE: The objective of this study is to explore the therapeutic effects and potential molecular mechanisms of JQC on CCl(4)-induced liver cirrhosis in mice, and to analyze its effects on the liver-gut axis, including liver pathology, the intestinal barrier, and gut microbiota. METHODS: To investigate the therapeutic effects of JQC and its impact on the liver-gut axis, a mouse model of liver cirrhosis was established by intraperitoneal injection of carbon tetrachloride (CCl(4)). The mice were allocated into four groups: the control group (without CCl(4) induction and receiving normal saline), the model group (CCl(4)-induced and receiving normal saline), and the two treatment groups which received JQC via gavage at either 500 mg/kg (JQC-H) or 250 mg/kg (JQC-L) after CCl(4) induction. Upon completion of the treatment, all mice were euthanized to collect serum, fecal samples, liver, and intestinal tissues for subsequent analysis. The assessments encompassed histopathology (H&E, Masson, Picro Sirius Red), immunohistochemistry, immunofluorescence, molecular biology (ELISA, Western blot, qRT-PCR), transcriptomics, and 16S rRNA sequencing. RESULTS: JQC ameliorated CCl(4)-induced liver cirrhosis in mice by improving liver function and suppressing fibrosis, inflammation, and oxidative stress. Mechanistically, it modulated the PI3K-AKT pathway and restored gut-liver axis homeostasis. This was evidenced by intestinal barrier repair (including upregulation of ZO-1 and occludin, and reduction of LPS) and correction of microbial dysbiosis, specifically enriching beneficial bacteria, such as Bacteroidota and Akkermansia, that correlated negatively with liver injury. CONCLUSION: This study demonstrates that JQC mitigates liver cirrhosis in mice by modulating the gut-liver axis, enhancing the intestinal barrier, and inhibiting the PI3K-AKT signaling pathway. These results propose JQC as a promising therapeutic candidate, warranting further clinical translation.