The vasoprotective effect of JP05 through the activation of PI3K/Akt-dependent eNOS and MEK/ERK pathways in brain endothelial cells.
OBJECTIVE
Endothelial dysfunction is involved in stroke. Recent therapeutic options for stroke have focused on the combination therapy with a polyherbal mixture. This study was designed to provide insight into the effects of JP05, a water extract of 12 herbs, on the levels of regulators in bEnd.3 mouse brain endothelial cells.


METHODS
Production of endothelial nitric oxide synthase (eNOS)-mediated nitric oxide (NO), the expression of vascular endothelial growth factor (VEGF) and the phosphorylations of eNOS, phosphatidylinositol 3-kinase (PI3K)/Akt, extracellular signal-regulated protein kinase (ERK) and cAMP response element binding protein (CREB) in JP05 were assayed in bEnd.3 cells, a mouse brain endothelial line.


RESULTS
JP05 led to increase the levels of eNOS-mediated NO generation and VEGF expression in bEnd.3 cells. JP05 induced the phosphorylation of eNOS, Akt and ERK in bEnd.3 cells. As well, JP05 blocked the inhibition of PI3K/Akt and ERK activities by LY294002 (PI3K/Akt inhibitor) and PD98059 (mitogen-activated protein kinase inhibitor), respectively. JP05 also induced the phosphorylation of CREB, which plays an important role in endothelial cell function and blood vessel development.


CONCLUSIONS
Taken together, these results indicate that JP05 can upregulate eNOS-mediated NO generation and VEGF expression through the ERK and/or PI3K/Akt activation, an upstream event of angiogenesis. JP05 with vasoprotective properties has a potential therapy for human brain diseases including stroke.
Son
Hye Young
HY
Oriental Medicine R&D Center, College of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea.
Jung
Hyo Won
HW
Kim
Won-Ki
WK
Park
Yong-Ki
YK
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases