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Inhibitory Effect of Dehydrozingerone on Vascular Smooth Muscle Cell Functions
Author(s) -
Sreejayan Nair,
Ren Jun
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb55-b
Subject(s) - vascular smooth muscle , platelet derived growth factor receptor , curcumin , biochemistry , cell growth , pharmacology , chemistry , microbiology and biotechnology , biology , endocrinology , growth factor , receptor , smooth muscle
Migration and proliferation of vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of atherosclerosis and re‐stenosis following balloon injury. Growth factors and reactive oxygen species released during vascular injury are thought activate VSMCs. We have recently reported that the food‐additive curcumin (diferuloyl methane) is a potent inhibitor of PDGF‐stimulated VSMC activation and neointima formation following balloon angioplasty. Dehydrozingerone, isolated from ginger (Zingiber officinale), is a structural half‐analog and a biosynthetic intermediate of curcumin with antiinflammatory and antioxidant properties. The objective of this study was to assess the ability of dehydrozingerone to inhibit PDGF‐stimulated migration, proliferation and collagen synthesis in cultured VSMCs. Dehydrozingerone (1–50 μM) produced a concentration‐dependent inhibition of PDGF‐elicited VSMC migration, proliferation, and collagen synthesis as assessed by chemotaxis, [ 3 H]thymidine‐incorporation and [ 3 H]‐L‐proline‐incorporation, respectively. At the molecular level dehydrozingerone attenuated agonist and hydrogen peroxide‐stimulated PDGF‐signal transduction and inhibited the hydrogen peroxide‐mediated oxidization of phosphotyrosine phosphatase. Equipotency of dehydrozingerone and curcumin in inhibiting PDGF signaling, and lack of activity of a structural analog isoeugenol suggests that the ketone group on the side chain and the phenolic and methoxy groups are a structural necessity for activity. These data suggest that dehydrozingerone is a potent inhibitor of key PDGF‐stimulated VSMC functions and may possess therapeutic implications in regulating these events following vascular injury.