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Honokiol up-regulates prostacyclin synthease protein expression and inhibits endothelial cell apoptosis
- Source :
- European Journal of Pharmacology. 554:1-7
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- Honokiol is a bioactive compound extracted from the Chinese medicinal herb Magnolia officinalis. We recently demonstrated that honokiol inhibited arterial thrombosis through stimulation of prostacyclin (PGI2) generation and endothelial cell protection. The current study is designed to investigate its mechanism of stimulation of PGI2 generation and cell protection. 6-keto-PGF1alpha, the stable metabolite of PGI2, in the media of rat aortic endothelial cells was measured with radioimmunoassay kits. Indomethacin, an inhibitor of cyclooxygenase (COX) and tranylcypromine, a prostacyclin synthease inhibitor were used to ascertain the target enzyme affected by honokiol. Prostacyclin synthease protein levels in endothelial cells were determined by Western blot analysis using an anti-PGI2 synthease rabbit polyclonal antibody. Flow cytometry was used to quantify the apoptotic cells and spectrophotometry was used to test the caspase-3 activity. Honokiol (0.376-37.6 microM) increased the level of 6-keto-PGF1alpha in the media of normal endothelial cells. It counteracted the inhibitory effect of tranylcypromine on the PGI2 generation, but did not influence the effect of indomethacin; evidently, honokiol up-regulated the expression of prostacyclin synthease in the endothelial cells. These effects showed perfect concentration-dependent behavior. In addition, at lower concentration (0.376-3.76 microM), honokiol significantly decreased the percentage of apoptotic endothelial cells induced by oxidized low-density lipoprotein (ox-LDL) and significantly lowered the activity of caspase-3 stimulated by ox-LDL. A high dose of honokiol (37.6 microM), however, failed to influence either of them. In conclusion, honokiol augments PGI2 generation in normal endothelial cells; its effect on PGI2 generation attributes to up-regulation of prostacyclin synthease expression; its cell protection may be correlated with its inhibition on apoptosis of endothelial cells. These findings have partly revealed the molecular mechanism of honokiol on inhibiting arterial thrombosis.
- Subjects :
- Male
Honokiol
Programmed cell death
Indomethacin
Cell
Apoptosis
Prostacyclin
Pharmacology
Biology
Gene Expression Regulation, Enzymologic
Lignans
Rats, Sprague-Dawley
chemistry.chemical_compound
Cytochrome P-450 Enzyme System
Fibrinolytic Agents
medicine
Animals
Cyclooxygenase Inhibitors
Cells, Cultured
Caspase 3
Biphenyl Compounds
Endothelial Cells
biology.organism_classification
Epoprostenol
Rats
Up-Regulation
Intramolecular Oxidoreductases
Endothelial stem cell
Magnolia officinalis
medicine.anatomical_structure
Biochemistry
chemistry
biology.protein
lipids (amino acids, peptides, and proteins)
Cyclooxygenase
Tranylcypromine
Drugs, Chinese Herbal
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 554
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....022aa16c334dac002de8a0ac0bddb8b7
- Full Text :
- https://doi.org/10.1016/j.ejphar.2006.09.065