Dachengqi decoction ameliorated liver injury in liver fibrosis mice by maintaining gut vascular barrier integrity.

BACKGROUND

Severe liver fibrosis may be accompanied by intestinal barrier damage, such as bacterial peritonitis, suggesting that the role of the gut-liver axis is nonnegligible. Dachengqi decoction (DCQD) was reported to improve bowel movements, but whether DCQD was effective for intestinal damage caused by liver fibrosis remained unclear.

PURPOSE: To investigate the role of DCQD in liver fibrosis-related gut vascular barrier (GVB) damage in mice.

STUDY

DESIGN

DCQD was verified to reduce the imbalance of the intestinal vascular barrier and restore intestinal homeostasis to prove that DCQD acts through the gut-liver axis.

METHODS

Three graded doses of DCQD were gavaged into the CCL4-induced mice for 12 weeks to evaluate the resistance to liver and intestinal damage. Immunoblotting and primary flow cytometry were used to assess organ damage; PV-1 to indicate gut vascular barrier damage; serum endotoxin, fecal SCFAs, and liver microbiota translocation to examine the gut-liver axis's crosstalk. Network pharmacology and RNA sequencing were used to analyze and verify the signaling pathway of DCQD.

RESULTS

DCQD significantly ameliorated fibrosis and inflammatory response in the CCL4-induced mice, alleviated gut leakage, downregulated PV-1, relieved liver enterobacterial translocation, restored intestinal homeostasis, and reduced infiltration of myeloid cells in the lamina propria. Network pharmacology and RNA sequencing results indicated that DCQD exerted anti-fibrotic and anti-inflammatory effects in the liver through inhibition of the ESR1/NF-κB/TNFα pathway and maintained GVB homeostasis through the FUT2/Wnt/β-Catenin pathway.

CONCLUSIONS

DCQD broke the closed-loop damage of the gut-liver axis to improve GVB injury in mice with liver fibrosis.