Callicarpa nudiflora is a traditional folk medicine in China used for eliminating stasis to subdue swelling. Several compounds from Callicarpa nudiflora have been proved to show anti-inflammatory, haemostasis, hepatitis, and anti-proliferative effects. Tumor endothelial cells play crucial roles in tumor-induced angiogenesis. Recently, it was demonstrated that ECs may be the important source of cancer associated fibroblasts (CAFs) through endothelial to mesenchymal transition (EndoMT). In this study, we evaluated the effects of nudifloside (NDF), a secoiridoid glucoside from Callicarpa Nudiflora, on TGF-β1-induced EndoMT and VEGF-induced angiogenesis, and the underlying mechanisms were also involved. It was found that NDF significantly inhibited enhanced migration, invasion and F-actin assembly in endothelial cells (ECs) exposed in TGF-β1. NDF obviously reversed expression of several biomarkers associated with EndoMT and recovered the morphological characteristics of ECs and tube-like structure induced by TGF-β1. Furthermore, treatment of NDF resulted in a significant destruction of VEGF-induced angiogenesis in vitro and ex vivo. Data from co-immunoprecipitation assay provided the evidence that Ezrin phosphorylation and the interaction with binding protein can be inhibited by NDF, which can be confirmed by data from Ezrin silencing assay. Collectively, the application of NDF inhibited TGF-β1-induced EndoMT and VEGF-induced angiogenesis in ECs by reducing Ezrin phosphorylation.

中文翻译：

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Nudifloside 是一种从紫珠中提取的环烯醚萜苷，通过抑制 Ezrin 磷酸化来抑制内皮细胞内皮细胞向间质转化和血管生成

裸花紫珠是我国传统民间药材，用于散瘀消肿。裸花紫珠的多种化合物已被证明具有抗炎、止血、肝炎和抗增殖作用。肿瘤内皮细胞在肿瘤诱导的血管生成中发挥着至关重要的作用。最近，有研究证明EC可能是通过内皮向间质转化（EndoMT）产生癌症相关成纤维细胞（CAF）的重要来源。在本研究中，我们评估了裸花紫珠中的环烯醚萜苷（NDF）对 TGF-β1 诱导的 EndoMT 和 VEGF 诱导的血管生成的影响，并探讨了其潜在机制。研究发现，NDF 显着抑制暴露于 TGF-β1 的内皮细胞 (EC) 中增强的迁移、侵袭和 F-肌动蛋白组装。 NDF明显逆转了与EndoMT相关的几种生物标志物的表达，并恢复了TGF-β1诱导的ECs和管状结构的形态特征。此外，NDF 的治疗导致 VEGF 诱导的体外和离体血管生成显着破坏。免疫共沉淀实验的数据提供了NDF可以抑制Ezrin磷酸化以及与结合蛋白的相互作用的证据，这可以通过Ezrin沉默实验的数据得到证实。总的来说，NDF 的应用通过减少 Ezrin 磷酸化抑制了 EC 中 TGF-β1 诱导的 EndoMT 和 VEGF 诱导的血管生成。