Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway

Rhein is a natural anthraquinone substance extracted from Rheum palmatum L. This study aimed to evaluate Rhein's protective effects against skin wound by in vivo and in vitro models and investigate whether its protective mechanism regulated the PI3K/AKT signaling pathway. The skin wound mice model was established and then treated with Rhein for 10 days. Hematoxylin and eosin staining and Masson's trichrome staining were applied to assess histological changes and collagen maturity in the mice skin wound tissues. Human skin fibroblasts (HSFs) viability, migration, and invasion were detected by Cell counting kit-8 (CCK-8), scratch wound, and transwell assays respectively. Moreover, the protein expression of p-PI3K, PI3K, p-AKT, and AKT were determined by western blot assay. We found that local treatment with Rhein promoted skin wound healing and accelerated collagen maturation, compared with the Model group. In addition, Rhein promoted skin wound healing through accelerated HSF proliferation, migration, and invasion. Furthermore, Rhein remarkably enhanced p-PI3K and p-AKT expression, as well as p-PI3K/PI3K and p-AKT/AKT ratio in skin wound mice and HSF cells, suggesting that Rhein promoted skin wound healing by activating PI3K/AKT signaling pathway. In conclusion, Rhein is a promising agent for promoting wound healing of skin tissues.