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石榴皮苷对人脐静脉内皮细胞炎症和血管生成激活的抑制作用。

Inhibitory Effect of Punicalagin on Inflammatory and Angiogenic Activation of Human Umbilical Vein Endothelial Cells.

作者信息

Liu Wei, Ou Yanghui, Yang Yumeng, Zhang Xuemei, Huang Liqi, Wang Xiaohua, Wu Buling, Huang Mingcheng

机构信息

Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University, Shenzhen, China.

Department of Digestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.

出版信息

Front Pharmacol. 2021 Nov 16;12:727920. doi: 10.3389/fphar.2021.727920. eCollection 2021.

DOI:10.3389/fphar.2021.727920
PMID:34867335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8636678/
Abstract

Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs and . Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.

摘要

石榴皮鞣质是从石榴中分离出的一种主要鞣花单宁，已被证明具有多种药理活性，但其治疗机制尚不明确。本研究的目的是证明石榴皮鞣质对人脐静脉内皮细胞（HUVECs）的抗炎和血管生成激活作用及其潜在机制。采用内皮细胞-白细胞黏附试验评估肿瘤坏死因子α（TNF-α）处理后人脐静脉内皮细胞原代培养物的激活情况。分别通过EdU试验、伤口迁移试验、跨内皮电阻（TEER）试验和毛细血管样管形成试验评估内皮细胞的增殖、迁移、通透性和管形成。此外，使用蛋白质印迹分析评估相关蛋白的表达。我们证实石榴皮鞣质可以减少人单核细胞与HUVECs的黏附。此外，石榴皮鞣质降低了HUVECs中ICAM-1和VCAM-1的mRNA和蛋白表达。此外，石榴皮鞣质抑制VEGF诱导的HUVECs的通透性、增殖、迁移和管形成，抑制IKK介导的TNF-α诱导的内皮细胞中NF-κB信号通路的激活，并抑制血管内皮生长因子受体2（VEGFR2）的激活和下游p-PAK1。我们的研究结果表明，石榴皮鞣质可能对HUVECs的激活具有保护作用，这表明石榴皮鞣质通过内皮介导的机制发挥作用，可用于治疗各种疾病，如癌症、类风湿性关节炎和心血管疾病。

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