Angelica dahurica promoted angiogenesis and accelerated wound healing in db/db mice via the HIF-1α/PDGF-β signaling pathway

Impaired angiogenesis is crucial for impeding the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that Angelica dahurica (A. dahurica) stimulated angiogenesis and benefited wound healing in genetic mouse models of diabetes. In HUVECs, A. dahurica promoted cell proliferation and tube formation, which was accompanied by increased nuclear translocation of HIF-1α under hypoxic conditions and led to elevated PDGF-β protein expression. A. dahurica activated the PI3K/AKT signaling pathway in human umbilical vein endothelial cells (HUVECs), which was abrogated by the PI3K inhibitor LY294002. Furthermore, the cellular expression of PDGF-β decreased significantly after treatment with a HIF-1α-siRNA, and PDGF-β expression was increased in HIF-1α-overexpressing cells. In a full-thickness cutaneous wound healing db/db mouse model, A. dahurica accelerated wound closure, which was reflected by a significantly reduced wound area and an increase in neovascularization, as well as by elevated PDGF-β expression and increased capillary formation. In addition, A. dahurica activated the PI3K/AKT signaling pathway and enhanced HIF-1α synthesis in wounds. In summary, A. dahurica promoted angiogenesis of HUVECs in vitro by promoting signaling via the HIF-1α/PDGF-β pathway, efficiently enhancing vascularization in regenerated tissue and facilitating wound healing in vivo. The results revealed that A. dahurica has potential as a therapy for vessel injury-related wounds.