title: Baicalin increases VEGF expression and angiogenesis by activating the ERR{alpha}/PGC-1{alpha} pathway.
abstract: OBJECTIVE
  Baicalin is the major component found in Scutellaria baicalensis root, a widely used herb in traditional Chinese medicine. Although it has been used for thousands of years to treat stroke, the mechanisms of action of S. baicalensis have not been clearly elucidated. In this report, we studied the modulation of angiogenesis as one possible mechanism by investigating the effects of these agents on expression of vascular endothelial growth factor (VEGF), a critical factor for angiogenesis.
  
  
  RESULTS
  The effects of baicalin and an extract of S. baicalensis on VEGF expression were tested in several cell lines. Both agents induced VEGF expression in all cells without increasing expression of hypoxia-inducible factor-1α (HIF-1α). The expression of reporter genes was also activated under the control of the VEGF promoter containing either a functional or a defective HIF response element (HRE). Only minimal effects were observed on reporter activation under the HRE promoter. Instead, both agents significantly induced oestrogen-related receptor (ERRα) expression as well as the activity of reporter genes under the control of ERRα-binding element. Their ability to induce VEGF expression was suppressed once ERRα expression was knocked down by siRNA or ERRα-binding sites were deleted in the VEGF promoter. We also found that both agents stimulated cell migration and vessel sprout formation from the aorta.
  
  
  CONCLUSIONS
  Our results implicate baicalin and S. baicalensis in angiogenesis by inducing VEGF expression through the activation of the ERRα pathway. These data may facilitate a better understanding of the potential health benefits of these agents in the treatment of cardiovascular diseases.
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.forename: Jianming
authors.initials: J
authors.lastname: Lu
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Leslie
authors.initials: L
authors.lastname: Smith-Powell
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Synold
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000196:embryology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D017930:Genes, Reporter; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots; D011401:Promoter Regions, Genetic / Q000187:drug effects; D034622:RNA Interference; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D031364:Scutellaria baicalensis; D015398:Signal Transduction / Q000187:drug effects*; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D043925:Angiogenesis Inducing Agents; D005419:Flavonoids; D006360:Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010936:Plant Extracts; D011960:Receptors, Estrogen; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000097983:ERRalpha Estrogen-Related Receptor; C497442:HIF1A protein, human; C486497:PPARGC1A protein, human; C467484:VEGFA protein, human; C038044:baicalin