Scutellarin Promotes In Vitro Angiogenesis Of Human Umbilical Vein Endothelial Cells

Objective: Scutellarin (Scu), a known flavonoid, is the primary active ingredientisolated from a Chinese herbal medicine Erigeron breviscapus (Vant.) Hand Mazz..Scutellarin has been proven to possess benefical actions for improving cardiovascularand cerebrovascular functions, and extensively used to treat various diseases whichare associated with endothelial cell dysfunction. However, it is unknown whetherscutellarin directly contributes to angiogenesis. In the present study, we evaluated theeffects of scutellarin on angiogenic potential, including endothelial cell proliferation,migration, invasion and capillary-like tube formation.Methods: Human umbilical vein endothelial cells (HUVECs) were treated withdifferent concentrations of scutellarin (1,5and10μmol/L). Cell proliferation wasevaluated with MTT assay. The effects of scutellarin on cell migration and invasionwere assessed by the wound healing assay and the Transwell chamber system,respectively. Capillary-like tube formation was studied with a Matrigel model. Thesemi-quantitative RT-PCR was used to determine the effects of scutellarin on themRNA levels of platelet endothelial cell adhesion molecule-1(PECAM-1), matrixmetalloproteinase-2(MMP-2) and its endogenous inhibitor-tissue inhibitor ofmetalloproteinase-2(TIMP-2). For protein levels, cells were subjected to Westernblotting and gelatin zymography to analyze the level and activity of PECAM-1andMMP-2, respectively.10ng/mL vascular endothelial growth factor (VEGF) was usedas a positive control.Results: Scutellarin induced endothelial proliferation, migration and invasion ina dose-dependent manner (p<0.05). In addition, scutellarin promoted capillary-liketube formation of HUVECs on Matrigel. These angiogenic activities of scutellarin at 10μmol/L were comparable to that of10ng/mL VEGF. Scutellarin also significantlyupregulated the protein and mRNA levels of PECAM-1(p<0.01). Furthermore,scutellarin strongly increased the mRNA expression and activity of MMP-2in aconcentration-dependent manner (p<0.01). The semi-quantitative RT-PCR showedthat scutellarin, at the dose of1μmol/L, reduced the mRNA level of TIMP-2(p<0.01).However, along with the concentration of scutellarin, TIMP-2mRNA expression wasgradually increased, but these were not statistically significant compared with controlcells (p>0.05).Conclusions: Scutellarin induces in vitro angiogenesis, upregulates theexpression of biochemical marker of angiogenesis-PECAM-1, and increases themRNA expression and activity of angiogenic factor-MMP-2. Thus, scutellarin shouldbe considered as a potential angiogenic inducer for ischemia-associated diseases aswell as wound healing.