Astragaloside IV Enhances Diabetic Wound Healing

Diabetes is a kind of chronic metabolic disease, which has become the world’s fourth-largest disease mortality. The greatest health threat of diabetic patients dues to its serious complications, such as wound delayed heal, diabetic kidney disease, retinopathy,peripheral neuropathy, in which refractory wounds are the research focus. Studies have shown astragaloside(AS-IV), as the main active ingredient of astragalus, plays an important role in anti-inflammatory and immunomodulatory aspects. This study intends to establish a model of wound healing in diabetic mice to explore the mechanism of AS-IV promoting skin tissue wound healing and provide a new idea to the treatment of clinical wound tissue.ObjectiveTo observe the role of AS-IV in wound healing of diabetic mice model, and study the immunomodulatory mechanism of AS-IV in acceleration of wound tissue repair; The effect of AS-IV on biological function of mouse fibroblasts(NIH3T3), such as proliferation and chemotaxis, is researched in vitro. At the same time the possible mechanisms to promote wound healing in diabetic mice tissue repair is also investigated.MethodsThe skin wound model of diabetic mice was established. We observed the effect of AS-IV on the area change of wound healing and the healing rate at different time points.ECM generation, new vessels and granulation tissue on local wound tissue were detected.The effect of AS-IV on biological function of NIH3T3 cells such as proliferation andchemotaxis was studied in vitro. The regulation of AS-IV on macrophage polarization was further explored.Results1. The effect of AS-IV on wound healing in diabetic miceAfter treatment with AS-IV, wound healing time was significantly shorter in diabetic mice. ECM deposition, new vessels and granulation tissue generation were significantly increased. In addition, levels of M2 macrophages were raised in skin wound tissue.2. The impact of AS-IV on the biological activity of NIH3T3 cellsAS-IV treatment enhanced the chemotaxis, proliferation and secretion function of NIH3T3 cells.3. The impact of AS-IV on macrophage polarizationAS-IV treatment alone could not affect macrophage polarization, but synergy with IL-13 can induce M2 macrophage polarization, and upregulate the expression of M2macrophage-associated molecules.4. To effect of AS-IV on the biological activity of NIH3T3 cells via M2 macrophagesAfter culture with supernatant of M2 macrophages, the chemotaxis, proliferation and secretion function of NIH3T3 cells were significantly increased, which effect was better than AS-IV alone. Experiments show M2 macrophages supernatant promoted the expression of TGF-β, which displayed a positive role on NIH3T3 cells via TGF-β signaling pathway.ConclusionAS-IV treatment accelerates the skin wound healing in diabetic mice. The potential mechanism may include that AS-IV contributes to M2 macrophage polarization, in turn affects the biological activities of fibroblast on chemotaxis, proliferation and secretion, and then accelerates the generation of ECM, new vessels and granulation tissue.