Inhibitory effects of scoparone from chestnut inner shell on platelet‐derived growth factor‐BB‐induced vascular smooth muscle cell migration and vascular neointima hyperplasia

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.

Bioactive phenolic components and potential health effects of chestnut shell: A review

“…Phenolic compounds in CIS also inhibited the migration of rat aortic smooth muscle cells (RASMC) induced by platelet-derived growth factor (PDGF) BB. In particular, scoparone in CIS inhibited RASMC cell migration and wound healing under PDGF-BB, but did not affect RASMC proliferation (Jung et al, 2019). This revealed the potential application of CIS as a new functional food and drug to prevent restenosis and atherosclerosis.…”

Effect of Endothelial Progenitor Cells Transplantation on Neointimal Hyperplasia and Reendothelialization after Balloon Catheter Injury in Rat Carotid Arteries

“…However, other scholars declared that transplanting EPCs could not only promote reendothelialization through paracrine modes of action, but also differentiate into mature ECs [40,41]. Assessment of transplanted EPCs and reendothelialization requires sequential crossor longitudinal sectioning of the vessels [42][43][44][45], but not every section could be chosen to stain and quantify [46][47][48]. The irregular geometry of the cell distribution requires accurate tools.…”

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

“…Furthermore, there is evidence that scoparone can mitigate cardiac ischemia/reperfusion injury in in vitro and in vivo settings ( 129 ). Scoparone also has anti-atherogenic effects including the inhibition of vascular smooth muscle cell proliferation and migration ( 130 , 131 ), inhibition of platelet aggregation ( 132 ), and the attenuation of atherosclerotic plaque formation and dyslipidemia in hyperlipidemic diabetic rabbits ( 133 , 134 ). One study also found that scoparone decreased peroxisome proliferator-activated receptor gamma (PPARγ) activity, expression of PPARγ target genes, and lipid accumulation in differentiating 3T3-L1 adipocytes ( 135 ).…”