Huiyang Shengji Extract improved wound healing by regulating macrophage phenotype transition

Dysfunction of macrophage phenotype transition is a primary reason for wound healing failure caused by persistent inflammation. Huiyang Shengji Extract (HSE) is a Traditional Chinese Medicine prescription for treating chronic wounds. Little is known about the underlying molecular mechanism of HSE. This study aim to investigate the effect of HSE on macrophage phenotype transition in chronic skin wound of mice and macrophages in vitro. Balb/c mice were randomly divided into four groups: control (normal wound-NS treated), model (delayed wound-NS treated), HSE-treated groups, and bFGF-treated groups. The immunosuppressive mice were operated by full-thickness excision. Macrophage phenotype markers on the wound were analyzed by immunohistochemistry, real-time PCR, and Western blot. The in vitro cytotoxicity and phagocytosis of macrophages was assessed by CCK-8 and neutral red assays. Macrophage 1/2 (M1/M2) markers were analyzed using ELISA, flow cytometry, and real-time PCR. The results showed delayed wound healing in immunosuppressed mice. HSE promoted macrophage recruitment to the wounded tissue, decreased the expression of iNOS and IL-6, and increased the level of CD206, VEGF, and TGF-β during granulation tissue formation. In vitro, HSE inhibited the inflammatory activated macrophages secreting M1 cytokines, promoted secretion of M2 cytokines, increased Arg-1 mRNA, and decreased iNOS mRNA significantly. In conclusion, an imbalance of macrophage phenotype contributed to impaired wound healing in immunosuppressed mice. HSE promoted impaired wound healing by regulating the macrophage phenotype transition: a potential therapeutic mechanism of HSE for the chronic non-healing wound.

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