MDL‐800, the SIRT6 Activator, Suppresses Inflammation via the NF‐<i>κ</i>B Pathway and Promotes Angiogenesis to Accelerate Cutaneous Wound Healing in Mice
Xiaoqi Jiang, Zhe Yao, Kangyan Wang, Lihua Lou, Kaikai Xue, Jinghao Chen, Guojian Zhang, Yu Zhang, Jiqing Du, Cai Lin, Jian Xiao
Abstract
Sirtuin 6 (SIRT6) is an NAD + ‐dependent deacetylase belonging to the sirtuin family. It has been shown to participate in wound healing and some inflammation‐related disorders. However, the effect of MDL‐800, a highly efficient and selective SIRT6 activator, on wound healing and inflammation has not been reported. Therefore, this study investigated whether MDL‐800 confers anti‐inflammatory effects and promotes wound healing and uncovered the molecular mechanisms involved. This was achieved using mouse models of full‐thickness wounds. Results showed that MDL‐800 significantly downregulated inflammation by attenuating the release of inflammatory mediators and improved collagen deposition and neovascularization of wounds, thereby accelerating cutaneous wound healing. Furthermore, MDL‐800 significantly downregulated expression levels of TNF‐ α and IL‐6 in the dorsal skin tissue of mice via the NF‐ κ B pathway. These results demonstrated that MDL‐800 exerted anti‐inflammatory and prohealing effects, indicating that the SIRT6/NF‐ κ B/I κ B signaling pathway may play an important role in wound healing.