Puerarin improves diabetic wound healing via regulation of macrophage M2 polarization phenotype

Abstract

Background: Skin wound healing depends on the progress of different but overlapping stages of healing, including hemostasis, inflammatory, proliferative and remodeling. Failure of these stages to occur in a timely and gradual manner may result in non-healing pathological wounds. Macrophages and neutrophils have been shown to play an essential role in the inflammatory responses of wound tissue, and their active plasticity allows them to modulate tissue damage and repair functions. The ability of macrophages and neutrophils to regulate the occurrence and resolution of inflammatory processes is essential for the treatment of pathological wound healing. Methods: Mice were categorized into negative control, streptozotocin, streptozotocin + puerarin and puerarin groups. The traditional Chinese medicine extract puerarin was selected to treat different groups of mice with a full-thickness skin defect wound. Cells of the RAW264.7 cell line were stimulated under different puerarin conditions. Then, real time quantitative polymerase chain reaction (RT-qPCR), western blot, immunofluorescence and other assays were carried out to explore the effect of puerarin on wound healing and its molecular mechanism. Results: Animal experiments found that the wound healing of diabetic mice treated with puerarin was significantly accelerated, and histological analysis found that puerarin treatment markedly decreased the infiltration of macrophages and neutrophils in wound tissue. Through western blot, RT-qPCR and immunofluorescence experiments, it was observed that puerarin treatment remarkably inhibited nuclear factor kinase B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, downregulated the expression of inflammatory cytokines and induced the M2 polarization of macrophages. At the cellular level, we also observed that puerarin improved M2 macrophage polarization and inhibited inflammatory pathway activation in a high-glucose culture. Conclusion: Puerarin has a significant therapeutic effect on wound healing in diabetic mice. The therapeutic effect is achieved by regulating macrophage polarization through suppressing NF-κB and MAPK signaling cascades.

Keywords

Macrophage / Puerarin / Wound healing / Diabetes / Skin / Streptozotocin / Traditional Chinese medicine / Nuclear factor kinase B / Mitogen-activated protein kinase

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