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In the present study, a novel polysaccharide, APS2-1, was isolated and purified from Astragalus membranaceus using DEAE-cellulose and Sephadex G-100 chromatography. The effect of APS2-1 on the promotion of wound healing was evaluated and its preliminary mechanism was investigated. In vitro experiments showed that APS2-1 was able to promote human skin fibroblast (HSF) propagation and accelerate cell cycle progression. For further examination, a scalded mice model was used to verify the effect of APS2-1 and investigate its mechanism of action. The analysis of biochemical parameters, including cyclin D1, inhibitor of nuclear factor κBα (IκBα), transforming growth factor (TGF)-β1, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) showed that APS2-1 inhibited the increase in cyclin D1 and IκBα, and promoted the expression of TGF-β1, bFGF and EGF, which was further confirmed by histopathological observation. These results suggested that APS2-1 possessed high potential in wound healing and its mechanism was associated with inhibiting inflammation, accelerating cell cycle and promoting the secretion of repair factors. [ABSTRACT FROM AUTHOR]