Wound healing can be improved by (—)‐epigallocatechin gallate through targeting Notch in streptozotocin‐induced diabetic mice

Delayed wound healing is one of the most prominent clinical manifestations of diabetes and lacks satisfactory treatment options. Persistent inflammation occurs in the late phase of wound healing and impairs the healing process in mice with diabetes mellitus (DM). In this study, we observed that the late wound healing in streptozotocin (STZ)-induced DM mice could be improved by (−)-epigallocatechin gallate (EGCG). The macrophage accumulation, inflammation response, and Notch signaling can be inhibited by EGCG in the skin wounds of DM mice. Furthermore, we found that the LPS-induced inflammation response including overactivated Notch signaling, was inhibited by EGCG in mouse macrophages. Moreover, we confirmed that EGCG could directly bind with mouse Notch-1. In addition, our studies indicated that diabetic wound healing was improved by EGCG treatment before or after the inflammation phase by targeting the Notch signaling pathway, which suggests that the pre-existing diabetic wound healing can be improved by EGCG. To summarize, wound healing can be improved by EGCG through targeting Notch in STZ-induced DM mice. Our findings provide insight into the therapeutic strategy for diabetic wounds and offer EGCG as a novel potential medicine to treat chronic wounds.—Huang, Y.-W., Zhu,Q.-Q., Yang,X.-Y., Xu,H.-H., Sun,B., Wang,X.-J., Sheng,J.Wound healing can be improved by (−)-epigallocatechin gallate through targeting Notch in streptozotocin-induced diabetic mice. FASEB J. 33, 953–964 (2019). www.fasebj.org