Wound Healing Effect of 20(S)-Protopanaxadiol of Ginseng Involves VEGF-ERK Pathways in HUVECs and Diabetic Mice

Wound healing is the process of skin and soft tissue repair following an injury. Angiogenesis is an essential process in wound healing and plays an important role in tissue regeneration. Ginseng is mainly composed of saponins and protopanaxadiol-based ginsenosides, namely Rb1, Rb2, Rc, Re, Rg1, and Rf. 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT) are aglycones of ginsenosides produced by metabolic processes and heat treatment. This study aimed to investigate the wound healing effects of active ingredients of ginseng, namely ginsenosides and aglycones, in various cellular and animal skin wound models. The angiogenic effects of ginsenosides were investigated in human umbilical vein endothelial cells (HUVECs). All experiments were conducted at increased intracellular glucose concentrations and the induction of angiogenesis through tube formation was evaluated. Among the ginsenosides and aglycones used in this study, PPD showed the strongest wound-healing activity. Cell scratch experiments confirmed that PPD increased intracellular proliferation and cell migration at high glucose concentrations, and western blotting of HUVECs showed that phosphorylated ERK, Akt, and p38 were regulated. We observed accelerated wound healing with PPD treatment in STZ-treated mice. Overall, the findings suggested that PPD could possibly help improve skin wound healing in patients with diabetes, although further research is recommended.