THE ROLE OF GINSENOSIDE RG1 IN AUGMENTING SURVIVAL OF THE ISCHEMIC SKIN FLAP: IN VITRO STUDIES OF CELL PROLIFERATION AND CAPILLARY TUBE FORMAION AND IN VIVO EFFECTS
Xiao Tian Wang, MD, Bella Avanessian, BS, Chuan Hao Chen, MD, Jin Bo Tang, MD, Paul Y Liu, MD.
Roger Williams Medical Center, Providence, RI, USA.
PURPOSE: A central event underlying wound-healing processes is angiogenesis, to which cellular proliferation and capillary tube formation are imperative. Ginsenoside Rg1, an important constituent of ginseng, is considered to be a promoter of angiogenesis. However, the role of Rg1 in promoting skin flap survival has not been investigated.
METHODS: In a culture model, we first tested the efficacy of Rg1 in promoting proliferation and capillary tube formation of HUVECs. Cell proliferation was assessed with MTS assay, and tube formation was recorded under a confocal microscope. Secondly, we studied the proliferation of cultured rat skin fibroblasts using an automated, non-invasive, live-cell imaging platform (IncuCyte) obtained over a week period. Finally, to assess effectiveness of Rg1 in vivo, 20 Sprague-Dawley rats were divided into 2 groups. 2.1ml of saline containing 0.2 mg of Rg1 was injected into flap territory of the treatment group. The flap was raised immediately after injection. In the control group, the flap was raised without preceding injections. One week later, flap viability was measured. Histologic sections were evaluated for vascularization and stained immunohistochemically with antibody to von Willebrand factor, a marker specific for angiogenesis.
RESULTS: Rg1 significantly enhanced the proliferation of HUVECs and promoted capillary tube formation in the culture setting. Addition of Rg1 significantly improved closure rates of the “wounds” in the monolayer of skin fibroblasts visualized using IncuCyte. In the rat model, flap viability was significantly improved with Rg1 injection compared to the non-treatment control (p<0.05). Histologically, vascularity was increased after R1 injection; immunohistochemical staining indicated enhanced expression of von Willebrand factor after Rg1 injection.
CONCLUSIONS: Use of Rg1 significantly improves proliferation of skin fibroblasts and increases ischemic flap survival in rat models. We postulate that Rg1 may induce the production of factors pertinent to angiogenesis, thus promoting angiogenesis and augmenting healing in the ischemic flap.