The flavonoid hydroxygenkwanin reduces inflammation and neointimal formation

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry Pub Date : 2024-09-18 DOI:10.1016/j.jnutbio.2024.109771

Pin-Yu Chen , Mao-Shin Lin , Chin-Chuan Chen , Yann-Lii Leu , Shu-Huei Wang

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Abstract

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play crucial roles in neointimal hyperplasia and restenosis progression in response to stimulation with various inflammatory cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and tumour necrosis factor-α (TNF-α). Hydroxygenkwanin (HGK) exerts remarkable anti-inflammatory, antitumour, antiproliferative and antimigratory effects. The aim of the study was to elucidate the therapeutic effect and regulatory mechanism of HGK on neointimal hyperplasia. The results showed that HGK inhibited the abnormal proliferation, migration, and inflammation of PDGF-BB- or TNF-α-treated VSMCs through regulation of the PDK1/AKT/mTOR pathway. In addition, HGK promoted circulating endothelial progenitor cell (EPC) chemotaxis. In an in vivo assay, HGK dramatically enhanced re-endothelization and reduced neointimal hyperplasia after femoral artery denudation with a guide wire in mice. These results suggest that HGK can serve as a therapeutic target drug or a functional food supplement for the treatment of restenosis.

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黄酮类羟基黄酮能减少炎症和新内膜的形成。

背景和目的：血管平滑肌细胞（VSMC）在血小板衍生生长因子-BB（PDGF-BB）和肿瘤坏死因子-α（TNF-α）等各种炎症细胞因子的刺激下，出现异常增殖和迁移，在新内膜增生和再狭窄进展中起着至关重要的作用。羟基花青素（HGK）具有显著的抗炎、抗肿瘤、抗增殖和抗移行作用。本研究旨在阐明 HGK 对新内膜增生的治疗作用和调控机制：方法：在体外进行 Western 印迹分析、细胞周期分析、MTT、BrdU 结合、伤口愈合和粘附试验，以确定 HGK 对 PDGF-BB 或 TNF-α 处理的 VSMC 的治疗效果。此外，还进行了对接分析和细胞热转移试验，以阐明 HGK 调节作用的机制。对断裂的股动脉进行组织学和免疫组化染色，以阐明HGK在体内的治疗效果：结果和结论：HGK通过调节PDK1/AKT/mTOR通路，抑制了PDGF-BB或TNF-α处理的VSMC的异常增殖、迁移和炎症反应。此外，HGK 还能促进循环内皮祖细胞（EPC）的趋化。在体内试验中，HGK 显著增强了小鼠股动脉导丝剥脱后的再内皮化并减少了新内膜增生。这些结果表明，HGK 可作为治疗再狭窄的靶向药物或功能性食品补充剂。

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来源期刊

Journal of Nutritional Biochemistry 医学-生化与分子生物学

CiteScore

9.50

自引率

3.60%

发文量

237

审稿时长

68 days

期刊介绍： Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.