Albiflorin Discovered from Paeoniae Rubra Radix Attenuates Liver Fibrosis and Inflammation via Regulating CXCL12/CXCR4 Axis

Liver fibrosis, a common pathological feature of chronic liver injury, faces a lack of effective treatment methods. Albiflorin (ALB), a pinane-type monoterpene compound isolated from the medicinal and edible plant Paeonia lactiflora Pall, has demonstrated a variety of biological activities. Here, we reported on the hepatoprotection and potential mechanisms of ALB against liver fibrosis. The results indicated that ALB significantly alleviated the histological damage and collagen deposition caused by CCl4-induced liver fibrosis and led to a reduction in serum levels of ALT, AST, CRE, and BUN. Meanwhile, ALB downregulated the expression of liver fibrosis markers (α-SMA and Collagen I) and decreased inflammatory cytokines (IL-1β, IL-6, TNF-α, and NLRP3). According to RNA-sequencing analysis, the CXCL12/CXCR4 axis was identified as a potential signaling pathway for ALB's action against liver fibrosis. Further mechanistic data revealed that ALB exerts anti-inflammatory and antifibrotic effects through the JAK1/STAT3 and p38 MAPK pathways mediated by the CXCL12/CXCR4 axis. Notably, treatment with AMD3100 diminished the hepatoprotective effect of ALB on CCl4-induced liver fibrosis. Furthermore, we found that the combination of ALB with metformin (MET) exhibited a significant synergistic effect in the treatment of liver fibrosis, with the CXCL12/CXCR4 axis playing a crucial role in this process. Thus, the findings of this study provided theoretical data support and suggested a new possible treatment strategy for liver fibrosis.