Inhibitory effects of oroxylin A on endothelial protein C receptor shedding in vitro and in vivo.

Abstract

Endothelial cell protein C receptor (EPCR) plays important roles in blood coagulation and inflammation. EPCR activity is markedly changed by ectodomain cleavage and release as the soluble EPCR. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Oroxylin A (OroA), a major component of Scutellaria baicalensis Georgi, is known to exhibit anti-angiogenic, antiinflammation, and anti-invasive activities. However, little is known about the effects of OroA on EPCR shedding. Data showed that OroA induced potent inhibition of phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and on cecal ligation and puncture (CLP)-induced EPCR shedding through suppression of TACE expression and activity. In addition, treatment with OroA resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results demonstrate the potential of OroA as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.

• Authors: Sae-Kwang Ku, Min-Su Han, Min Young Lee, You-Mie Lee, Jong-Sup Bae
• Journal: BMB reports (BMB Rep) Vol. 47 Issue 6 Pg. 336-41 (Jun 2014) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 24286327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Coagulation Factors
• Flavonoids
• Interleukin-1beta
• Receptors, Cell Surface
• Tumor Necrosis Factor-alpha
• activated protein C receptor
• 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human
• Adam17 protein, mouse
• Tetradecanoylphorbol Acetate

Topics

• ADAM Proteins (metabolism)
• ADAM17 Protein
• Animals
• Blood Coagulation Factors (metabolism)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Flavonoids (chemistry, pharmacology, therapeutic use)
• Human Umbilical Vein Endothelial Cells
• Humans
• Interleukin-1beta (pharmacology)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Phosphorylation (drug effects)
• Receptors, Cell Surface (metabolism)
• Scutellaria baicalensis (chemistry, metabolism)
• Sepsis (drug therapy, etiology, metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)