title: Protocatechuic acid induces angiogenesis through PI3K-Akt-eNOS-VEGF signalling pathway.
abstract: In this study, we sought to elucidate whether protocatechuic acid contributes to induce angiogenesis as well as its mechanisms. To this end, we examined the role of protocatechuic acid on human brain microvascular endothelial cell line (HBMEC) proliferation, invasion and tube formation in in vitro. For the study of mechanisms involved, the phosphoinositide 3 kinase (PI3K)-Akt inhibitor LY294002, the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME, vascular endothelial growth factor (VEGF), antagonist sFlt-1 and VEGF receptor blocker SU-1498 were used. Proliferation of HBMEC was tested by MTT. Scratch adhesion test was used to assess the ability of invasion. A Matrigel tube formation assay was performed to test capillary tube formation ability. PI3K-Akt-eNOS-VEGF pathway activation in HBMEC was tested by Western blot. Our data suggested that protocatechuic acid induces angiogenesis in vitro by increasing proliferation, invasion and tube formation. VEGF expression was increasing by protocatechuic acid and counteracted by VEGF antagonist sFlt-1, LY294002 and L-NAME in HBMEC. Tube formation was increased by protocatechuic acid and counteracted by VEGF receptor blocker-SU1498, LY294002 and L-NAME. These data suggest that protocatechuic acid may be a candidate therapy for stroke recovery by promoting angiogenesis via a programmed PI3K/Akt/eNOS/VEGF signalling axis.
authors.affiliation: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai, China.
authors.forename: Zechun
authors.initials: Z
authors.lastname: Kang
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhu
authors.forename: Wanglin
authors.initials: W
authors.lastname: Jiang
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
mesh_terms: D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D002867:Chromones; D002934:Cinnamates; D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; D009025:Morpholines; C483044:SU 1498; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C009091:protocatechuic acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3; D019331:NG-Nitroarginine Methyl Ester