题名：Ellagic acid inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and prevents atheroma formation in streptozotocin-induced diabetic rats.
作者：RANI UP; KESAVAN R; GANUGULA R; AVANEESH T; KUMAR UP; REDDY GB; DIXIT M;
来源：J Nutr Biochem. 2013 Nov;24(11):1830-9. doi: 10.1016/j.jnutbio.2013.04.004. Epub [ IF= 0.00 ] ]
摘要：Plant-derived polyphenolic compounds have beneficial health effects. In the
present study, we determined the ability of ellagic acid (EA) to prevent
platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of primary
cultures of rat aortic smooth muscle cells (RASMCs). We also determined the
ability of EA to prevent atherosclerosis in streptozotocin-induced diabetic rats.
Proliferation of cells was measured via Alamar Blue assay and through propidium
iodide-based cell cycle analysis in flow cytometer. Reactive oxygen species (ROS)
were measured via 2',7'-dichlorofluorescin diacetate and Amplex red methods.
Expression of proliferation markers and activation of kinases were assessed by
immunoblot analysis. Cotreatment of primary cultures of RASMCs with 25 mumol/L of
EA significantly reduced PDGF-BB (20 ng/ml)-induced proliferation by blocking
S-phase entry. EA effectively blocked PDGF receptor-beta (PDGFR-beta) tyrosine
phosphorylation, generation of intracellular ROS and downstream activation of
extracellular signal-regulated kinase 1/2. It also blocked PDGF-BB-induced
expression of cyclin D1. Computational molecular docking of EA with the
PDGFR-beta-PDGF-BB complex revealed two putative inhibitor binding sites which
showed similar binding energies with the known PDGFR-beta inhibitor AG1295. In
diabetic rats, supplementation of diet with 2% EA significantly blocked
diabetes-induced medial thickness, and lipid and collagen deposition in the arch
of aorta. These were assessed through haematoxylin and eosin, Oil Red O and
Masson's trichome staining, respectively. EA treatment also blocked cyclin D1
expression in medial smooth muscle cells in experimental animals. Thus, EA is
effective in reducing atherosclerotic process by blocking proliferation of
vascular smooth muscle cells.