No abstract

BACKGROUND: Compounds of the inner shell of chestnut (Castanea crenata) have diverse biological activities, including anti-cancer and anti-oxidant activities. Here we explored the effects of an extract of chestnut inner shells and of its bioactive component scoparone on vascular smooth muscle cell migration and vessel damage. RESULTS:The ethanol extract of chestnut inner shells, containing 11 major compounds, inhibited platelet-derived growth factor (PDGF)-BB-induced migration of rat aortic smooth muscle cells (RASMCs). Among these compounds, scoparone (6,7-dimethoxycoumarin) suppressed RASMC migration and wound healing in response to PDGF-BB but did not affect RASMC proliferation. In RASMCs, scoparone inhibited the PDGF-BB-induced rat aortic sprout outgrowth and attenuated the PDGF-BB-mediated increase in phosphorylation of mitogen-activated protein kinases (MAPKs), p38 MAPK and extracellular signal-regulated kinase 1/2. The in vivo administration of scoparone resulted in the attenuation of neointima formation in balloon-injured carotid arteries of rats.CONCLUSION: These findings demonstrate that scoparone, found in chestnut inner shells, may inhibit cell migration through suppression of the phosphorylation of MAPKs in PDGF-BB-treated RASMCs, probably contributing to the reduction of neointimal hyperplasia induced after vascular injury. Therefore, scoparone and chestnut inner shell may be a potential agent or functional food, respectively, for the prevention of vascular disorders such as vascular restenosis or atherosclerosis. Cell isolation and cultureAll experiments were performed, and animal care was undertaken, in accordance with the institutional guidelines of Konkuk University. RASMCs were isolated from the thoracic aortas of five-week-old male Sprague Dawley (SD) rats (n = 6) and were cultivated in Dulbecco's modified Eagle medium (DMEM; Welgene, Korea) supplemented with 10% fetal bovine serum (FBS), 100 U mL −1 penicillin, 100 mg mL −1 streptomycin, and 200 mmol L −1 L-glutamine. For all experiments, RASMCs at passages 5-8 were grown to 70-80% confluence.