The vasoprotective effect of JP05 through the activation of PI3K/Akt-dependent eNOS and MEK/ERK pathways in brain endothelial cells

Hye Young Son, Hyo Won Jung, Won-Ki Kim, Yong Ki Park

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aim of the study: 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. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)607-613
Number of pages7
JournalJournal of Ethnopharmacology
Volume130
Issue number3
DOIs
Publication statusPublished - 2010 Aug 1

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Phosphatidylinositol 3-Kinase
MAP Kinase Signaling System
Nitric Oxide Synthase Type III
Endothelial Cells
Vascular Endothelial Growth Factor A
Brain
Cyclic AMP Response Element-Binding Protein
Nitric Oxide
Stroke
Phosphorylation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Extracellular Signal-Regulated MAP Kinases
Brain Diseases
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Protein Kinases
Blood Vessels
Up-Regulation
Therapeutics
Water

Keywords

  • Brain endothelial cell
  • ENOS
  • JP05
  • NO
  • PI3K/Akt
  • VEGF

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

The vasoprotective effect of JP05 through the activation of PI3K/Akt-dependent eNOS and MEK/ERK pathways in brain endothelial cells. / Son, Hye Young; Jung, Hyo Won; Kim, Won-Ki; Park, Yong Ki.

In: Journal of Ethnopharmacology, Vol. 130, No. 3, 01.08.2010, p. 607-613.

Research output: Contribution to journalArticle

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