Jiujiu Li^{1, 2}, Ting Wang¹, Fuding Zhou¹, Changchun Xiao², Zhengxiang Liu¹, Jinchuan Yu¹, Di Liang³, Guangjun Wang⁴, Changsheng Shao⁵, Peng Wang^5,, Wenjun Chen^1,

From liver injury to hepatocirrhosis and hepatocarcinoma, irreversible progression correlates closely with inflammation. Polygonatum sibiricum has been reported to be beneficial to the liver, but its regulation of inflammation in liver injury has not been determined. Thus, we hypothesize that Polygonatum sibiricum polysaccharides (PSP) play a protective role against acute liver injury by inhibiting inflammation and explore the underlying mechanism. The concentration and constituents of polysaccharides in PSP were identified first. We found that, like bifendate, PSP pretreatment significantly ameliorated acute CCl₄ exposure-induced liver injury and associated biomarkers. Meanwhile, PSP markedly attenuated inflammation and macrophage proinflammatory polarization both in the livers of CCl₄-treated mice and LPS-treated Raw264.7 cells. Mechanistic investigation showed that PSP pretreatment markedly attenuated the activation of JAK₂/STAT₃/NF-κB signaling pathway in liver injury. Our findings demonstrated a novel understanding of PSP-mediated macrophage proinflammatory polarization in acute injury, which provides new knowledge regarding its application in acute liver injury treatment.

Polygonatum sibiricum, macrophage M1 polarization, acute liver injury, inflammation, JAK₂/STAT₃