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

• DCQD alleviated liver fibrosis and its associated gut vascular barrier (GVB) injury. • DCQD protects against liver and GVB injury via the gut-liver axis. • Network pharmacology showed that DCQD alleviated liver fibrosis by inhibiting ESR1 and NF-κB/TNFα pathways. • RNA sequencing showed that DCQD alleviated GVB by upregulating FUT2 and Wnt/β-Catenin signaling. 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. To investigate the role of DCQD in liver fibrosis-related gut vascular barrier (GVB) damage in mice. 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. Three graded doses of DCQD were gavaged into the CCL 4 -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. DCQD significantly ameliorated fibrosis and inflammatory response in the CCL 4 -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. DCQD broke the closed-loop damage of the gut-liver axis to improve GVB injury in mice with liver fibrosis. DCQD inhibited the progression of hepatic fibrosis and attenuated gut vascular barrier damage in CCL 4 mice by modulating the ESR1/NF-κB/TNFα pathway in the liver and the FUT2/Wnt/β-Catenin pathway in the ileum.