Division of Life Science and Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
Shenzhen Key Laboratory of Edible and Medicinal Bioresources, Ski, The Hong Kong University of Science and Technology, Hi-Tech Park, Nanshan, Shenzhen, China; Division of Life Science and Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
Phytomedicine. 2018 Mar 15;42:135-143. doi: 10.1016/j.phymed.2018.03.029. Epub 2018 Mar 17.
Polygoni Cuspidati Rhizoma et Radix (PCRR; the root and rhizome of Polygonum cuspidatum Sieb. et Zucc) is a traditional Chinese medicine for the treatment of inflammation, hyperlipemia, favus, jaundice and scald.
HYPOTHESIS/PURPOSE: The extract of PCRR inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis. The hypothesis is supported by analysis of PCRR extract and investigation of pharmacological role and signaling mechanism of PCRR extract in regulating angiogenic responses.
The PCRR ethanolic extract was examined for its inhibitory effects on angiogenesis based on VEGF-treated human umbilical vein endothelial cells and in zebrafish model METHODS: The effects and signaling mechanism of a standardized ethanolic extract of PCRR were tested on cell proliferation, migration and tube formation in VEGF-treated human umbilical vein endothelial cells, and which was further validated in zebrafish embryo model.
The treatment of PCRR extract in cultured endothelial cells inhibited VEGF-induced cell proliferation, cell migration and tube formation in a dose-dependent manner and also suppressed the formation of sub-intestinal vessels in zebrafish embryos. Moreover, the applied PCRR extract suppressed VEGF-induced phosphorylations of VEGF receptor 2 (VEGFR2) and JNK. Thus, the site of effect triggered by PCRR was proposed to be mediated by VEGFR2. To further support this notion, the phosphorylations of Erk, Akt and eNOS, induced by VEGF, were markedly reduced under the challenge of PCRR extract: the reductions were subsequently further decreased in the present of inhibitors of Erk, Akt and eNOS. In parallel, the formation of ROS induced by VEGF in cultured endothelial cells was markedly reduced in the present of PCRR extract.
Collectively, our studies demonstrated the pharmacological role and signaling mechanism of PCRR in regulation of angiogenic responses, which supported further evaluation and development of PCRR as a potential therapeutic agent for the treatment and prevention of diseases related with angiogenesis.
虎杖（Polygonum cuspidatum Sieb. et Zucc. 的根和根茎）是一种传统的中药，用于治疗炎症、高脂血症、头癣、黄疸和烫伤。
假设/目的：虎杖提取物抑制血管内皮生长因子（VEGF）诱导的血管生成。该假设得到了虎杖提取物分析和虎杖提取物调节血管生成反应的药理作用和信号机制研究的支持。
基于 VEGF 处理的人脐静脉内皮细胞和斑马鱼模型，研究了虎杖乙醇提取物对血管生成的抑制作用。
测试了一种标准化的虎杖乙醇提取物对 VEGF 处理的人脐静脉内皮细胞中细胞增殖、迁移和管状形成的作用和信号机制，并在斑马鱼胚胎模型中进一步验证。
虎杖提取物在培养的内皮细胞中的处理以剂量依赖性方式抑制 VEGF 诱导的细胞增殖、细胞迁移和管状形成，并且还抑制了斑马鱼胚胎中次级肠血管的形成。此外，所应用的虎杖提取物抑制了 VEGF 诱导的血管内皮生长因子受体 2（VEGFR2）和 JNK 的磷酸化。因此，虎杖触发的作用部位被提议通过 VEGFR2 介导。为了进一步支持这一观点，VEGF 诱导的 Erk、Akt 和 eNOS 的磷酸化在虎杖提取物的挑战下明显降低：在 Erk、Akt 和 eNOS 的抑制剂存在下，这些降低进一步减少。平行地，VEGF 在培养的内皮细胞中诱导的 ROS 的形成在虎杖提取物的存在下明显减少。
总之，我们的研究表明了虎杖在调节血管生成反应中的药理作用和信号机制，这支持了进一步评估和开发虎杖作为治疗和预防与血管生成相关疾病的潜在治疗剂。
