Xiayuxue Decoction Plays an Antidevelopment Role in Hepatocellular Carcinoma through Intestinal-Hepatic Axis

Introduction: In recent years, the effect of “intestinal-hepatic axis” in tumorigenesis of hepatocellular carcinoma (HCC) has been paid more and more attention, and the imbalance of gut microbiota is closely related to the pathogenesis of HCC. The Xiayuxue decoction (XYXD) has inhibitory effect on hepatic fibrosis, but the effect of XYXD on HCC is not clear. Methods: We induced HCC mouse model by diethylnitrosamine and CCL4. HCC mice were treated with XYXD gavage. Hematoxylin-eosin staining was used to detect the pathological changes of liver tissue in mice. Immunohistochemistry was used to detect the level of Ki-67 in liver tumor and ZO-1 in colon tissue. The level of inflammatory factors in plasma, liver, and colon tissue of mice was detected by ELISA. The changes of macrophages and neutrophils in colorectal tissues of mice were counted by immunofluorescence. 16S sequencing was used to analyze the effect of XYXD treatment on gut microbiota of HCC mice. Results: Our study found that XYXD could inhibit the progress of HCC. XYXD upregulated the expression levels of ZO-1, occludin, and claudin in colon tissue to repair intestinal mucosal barrier. XYXD could alleviate the infiltration of intestinal immune cells in HCC mice by inhibiting the data of macrophages and neutrophils in colon tissue and downregulating SIgA level. XYXD also regulated the composition of intestinal microorganisms and improved the diversity of gut microbiota, thus affecting the progress of HCC. Conclusion: XYXD inhibits the progress of HCC by influencing gut microbiota to regulate intestinal and liver inflammation and intestinal immune response.