Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China.
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Life Sci. 2019 Apr 15;223:128-136. doi: 10.1016/j.lfs.2019.03.026. Epub 2019 Mar 12.
Liquorice is a widely used herbal medicine for treating various diseases native to southern Europe and parts of Asia. Isoliquiritin (ISL), a licorice root-derived flavonoid, has been reported to exhibit antioxidant, anti-inflammatory, anti-genotoxic activity and anti-depression activities. This study was aimed to explore the pro-angiogenic activity of ISL and explicate the underlying mechanism.
In vitro, ISL-treated human umbilical vein endothelial cells (HUVECs) were analyzed for cell viability, cell migration and tube formation. In vivo, pro-angiogenic effects were evaluated for the intersegmental vessels (ISVs) formation in transgenic zebrafish embryos [Tg(fli-1: EGFP)]. Furthermore, a blocking assay with eight pathways-specific kinase inhibitors were also used to determine the potential pro-angiogenic mechanism of ISL.
ISL counteracted tyrosine kinase inhibitor II (VRI)-induced endothelial cell apoptosis and promoted cell migration and tube formation in HUVECs. ISL markedly rescued ISVs loss induced by VRI in zebrafish embryos, probably by activating vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K), Raf and mitogen-activated protein kinase (MEK)-dependent signaling pathways.
Our study first discovered and confirmed the pro-angiogenic activity of ISL both in HUVECs and zebrafish. Thus, ISL could be developed as a potential therapeutic agent by the role of pro-angiogenic activity for the treatment of cardiovascular diseases, cerebrovascular diseases and other vascular diseases.
甘草是一种广泛用于治疗源自欧洲南部和亚洲部分地区的各种疾病的草药。甘草根衍生的异甘草素（ISL）已被报道具有抗氧化、抗炎、抗遗传毒性和抗抑郁活性。本研究旨在探讨 ISL 的促血管生成活性，并阐明其潜在的机制。
在体外，分析 ISL 处理的人脐静脉内皮细胞（HUVEC）的细胞活力、细胞迁移和管形成。在体内，通过转基因斑马鱼胚胎[Tg(fli-1: EGFP)]中的节间血管（ISV）形成评估促血管生成作用。此外，还使用八种途径特异性激酶抑制剂的阻断试验来确定 ISL 的潜在促血管生成机制。
ISL 拮抗酪氨酰激酶抑制剂 II（VRI）诱导的内皮细胞凋亡，并促进 HUVEC 中的细胞迁移和管形成。ISL 显著挽救了 VRI 诱导的斑马鱼胚胎中 ISV 的缺失，可能通过激活血管内皮生长因子受体-2（VEGFR-2）、磷酸肌醇 3-激酶（PI3K）、Raf 和丝裂原激活蛋白激酶（MEK）依赖性信号通路。
本研究首次在 HUVEC 和斑马鱼中发现并证实了 ISL 的促血管生成活性。因此，ISL 可通过其促血管生成活性作用开发为治疗心血管疾病、脑血管疾病和其他血管疾病的潜在治疗剂。
