Anti-Inflammatory Effect of Cherry Extract Loaded in Polymeric Nanoparticles: Relevance of Particle Internalization in Endothelial Cells
Anti-Inflammatory Effect of Cherry Extract Loaded in Polymeric Nanoparticles: Relevance of Particle Internalization in Endothelial Cells
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DOI：
10.3390/pharmaceutics11100500
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发表时间：
2019-10-01
期刊：
影响因子：
5.4
通讯作者：
Di Stefano, Rossella
中科院分区：
文献类型：
--
作者：
Beconcini, Denise;Felice, Francesca;Di Stefano, Rossella
本研究旨在评估天然樱桃提取物（CE）（无论是游离的还是封装在基于壳聚糖衍生物（Ch-der）或聚（乳酸-乙醇酸）（PLGA）的纳米颗粒（NP）中对人脐静脉内皮细胞（HUVEC）的抗炎作用。对来自 Prunus avium L. 的 CE 进行了总多酚、类黄酮和花青素含量的表征。通过水溶性四唑盐 (WST-1) 测定检测 CE 和负载 CE 的 NP 对脂多糖 (LPS) 应激的 HUVEC 的细胞毒性和保护作用。通过酶联免疫吸附测定 (ELISA) 对 HUVEC 释放的促炎和抗炎细胞因子（TNF-α、IL-6、IL-10 和 PGE2）进行定量。所有 NP 类型在孵育 2 小时后均内化到 HUVEC 中，并在 2 μg 没食子酸当量 (GAE)/mL 浓度下促进游离 CE 的抗炎作用。负载 CE 的 Ch-der NP 显示出最高的体外摄取和抗炎活性，可抑制 IL-6、TNF-α 和 PGE2 细胞因子的分泌。此外，所有NPs都能减少一氧化氮和NLRP3炎症小体的产生，并且比主要皮质类固醇地塞米松具有更强的抗炎作用。特别是，结果表明，当天然 CE 封装在基于季铵壳聚糖的 NP 中时，可以保护内皮细胞免受炎症应激。 CE 的有益效果与负载 CE 的 NP 的体外内化直接相关。
This study aimed at evaluating the anti-inflammatory effect of natural cherry extract (CE), either free or encapsulated in nanoparticles (NPs) based on chitosan derivatives (Ch-der) or poly(lactic-co-glycolic acid) (PLGA), on human umbilical vein endothelial cells (HUVEC). CE from Prunus avium L. was characterized for total polyphenols, flavonoids, and anthocyanins content. CE and CE-loaded NP cytotoxicity and protective effect on lipopolysaccharide (LPS)-stressed HUVEC were tested by water-soluble tetrazolium salt (WST-1) assay. Pro- and anti-inflammatory cytokines (TNF-alpha, IL-6, IL-10, and PGE2) released by HUVEC were quantified by enzyme-linked immunosorbent assay (ELISA). All NP types were internalized into HUVEC after 2 h incubation and promoted the anti-inflammatory effect of free CE at the concentration of 2 mu g gallic acid equivalents (GAE)/mL. CE-loaded Ch-der NPs showed the highest in vitro uptake and anti-inflammatory activity, blunting the secretion of IL-6, TNF-alpha, and PGE2 cytokines. Moreover, all NPs reduced the production of nitric oxide and NLRP3 inflammasome, and had a stronger anti-inflammatory effect than the major corticosteroid dexamethasone. In particular, the results demonstrate that natural CE protects endothelial cells from inflammatory stress when encapsulated in NPs based on quaternary ammonium chitosan. The CE beneficial effects were directly related with in vitro internalization of CE-loaded NPs.