SBD.4 stimulates regenerative processes in vitro, and wound healing in genetically diabetic mice and in human skin/severe-combined immunodeficiency mouse chimera.

In search of novel angiostimulators, we performed a high-throughput screening of medicinal plants beneficial for blood circulation. From the panel of positive hits, Angelica sinensis was selected for further investigation. Purified down to a low-molecular-weight fraction and characterized by high-performance liquid chromatography-mass spectrometry, the material, named SBD.4A, revealed a particularly strong wound healing activity in the diabetic mouse wound-healing model, and in the human/severe combined immunodeficiency mouse chimera wound-healing model. In both models, SBD.4A compared favorably with the Food and Drug Administration-approved wound-healing drug becaplermin, suggesting that this botanical product could be a valuable treatment for difficult-to-heal wounds. Further high-performance liquid chromatography fractionation of SBD.4A yielded a hydrophilic fraction, which strongly stimulated endothelial cell proliferation, tridimensional endothelial cell network formation, as well as the proliferation of human dermal fibroblasts and type I collagen secretion. Because angiogenesis and fibroblast proliferation are essential for wound healing, we propose that this liquid chromatography-mass spectrometry-defined hydrophilic fraction is at least partially responsible for the wound-healing activity of SBD.4A.