WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
Food Chem. 2013 Dec 15;141(4):3309-16. doi: 10.1016/j.foodchem.2013.06.038. Epub 2013 Jun 18.
The unregulated migration and invasion of human aortic smooth muscle cells (HASMCs) into the intima is a crucial step in the development of atherosclerosis. Recently, the oriental persimmon extract (Diospyros kaki Thunb. cv. Fuyu) has been investigated for its anti-atherogenic properties, but the molecular mechanisms involved remain unclear. We investigated the inhibitory effects of persimmon peel and flesh extract on the platelet-derived growth factor (PDGF) BB-induced MMP-1 expression using Western blot, and abnormal migration and invasion of HASMCs using a modified Boyden chamber assay and a wound healing assay. We also evaluated the inhibitory effects of persimmon peel extract on aortic vessel thickening using a rat aortic sprouting assay. Persimmon peel (PPE), but not flesh extract (PFE), inhibited PDGF-BB-induced MMP-1 expression, cell migration and invasion in HASMCs, while suppressing the rat aortic sprouting. Western blot and in vitro kinase assay data demonstrated that PPE inhibited Src kinase activity and subsequently attenuated PDGF-BB-induced phosphorylation of MAPK and Akt signalling pathways. Taken together, our results indicate that persimmon peel might possess a potential anti-atherogenic effect through attenuation of ASMCs migration and invasion and aortic sprouting by direct inhibition of the c-Src kinase activity.
人主动脉平滑肌细胞（HASMC）不受调节的迁移和浸润到内膜是动脉粥样硬化发展的关键步骤。最近，东方柿子提取物（Diospyros kaki Thunb. cv. Fuyu）因其抗动脉粥样硬化特性而受到研究，但涉及的分子机制仍不清楚。我们使用 Western blot 研究了柿子皮和果肉提取物对血小板衍生生长因子（PDGF）BB 诱导的 MMP-1 表达的抑制作用，并使用改良 Boyden 室测定和划痕愈合测定研究了 HASMC 异常迁移和侵袭。我们还使用大鼠主动脉发芽测定评估了柿子皮提取物对主动脉壁增厚的抑制作用。柿子皮（PPE），而不是果肉提取物（PFE），抑制了 PDGF-BB 诱导的 HASMC 中 MMP-1 的表达、细胞迁移和侵袭，同时抑制了大鼠主动脉发芽。Western blot 和体外激酶测定数据表明，PPE 抑制了 Src 激酶活性，随后减弱了 PDGF-BB 诱导的 MAPK 和 Akt 信号通路的磷酸化。总之，我们的结果表明，柿子皮可能通过直接抑制 c-Src 激酶活性，减弱 ASMC 迁移和侵袭以及主动脉发芽，从而具有潜在的抗动脉粥样硬化作用。
