Panacis Quinquefolii Radix glucan ameliorates liver fibrosis by modulating macrophage polarization and suppressing inflammation via the TLR4/MyD88/NF-κB signaling pathway

Abstract Liver fibrosis is a critical pathological stage in chronic liver disease progression, with effective clinical therapeutics remaining limited. Herein, a homogeneous glucan (XYS1-1, 12.59 kDa) was isolated and purified from Panax quinquefolius Radix roots-a widely used medicinal and functional food ingredient. Structural characterization via monosaccharide composition, IR, methylation analysis, and 2D-NMR confirmed XYS1-1 has a →4)-α-D-Glcp-(1→ backbone with terminal α-D-Glcp branches at C-6 positions, distinguishing it from commercial starches as a potential functional hydrocolloid. In vitro (TGF-β1-induced LX-2 cells) and in vivo (CCl₄-induced fibrotic mice) assays demonstrated that XYS1-1 alleviated liver fibrosis in a concentration-dependent manner-outperforming the clinical reference Fuzheng Huayu Capsule in reducing α-SMA/collagen expression, serum ALT/AST levels, and hepatic pathological injury. Mechanistically, XYS1-1 exerted antifibrotic effects by suppressing macrophage inflammatory responses, regulating M1/M2 polarization, and inhibiting the TLR4/MyD88/NF-κB pathway. These findings highlight XYS1-1, as a promising candidate for functional foods targeting liver health, while expanding insights into natural polysaccharide-based strategies against liver fibrosis.