Zhu Xia, Okubo Aya, Igari Naoki, Ninomiya Kentaro, Egashira Yukari
Research and Development Department, Daiwa Pharmaceutical Co., Ltd., 1650-88 Okubara-cho, Ushiku-shi, Ibaraki 300-1283, Japan.
Marketing Planning & Support, Daiwa Pharmaceutical Co., Ltd., Tokyo, Japan.
Biosci Microbiota Food Health. 2017;36(2):45-53. doi: 10.12938/bmfh.16-016. Epub 2016 Dec 27.
Angiogenesis is implicated in diverse pathological conditions such as cancer, rheumatoid arthritis, psoriasis, atherosclerosis, and retinal neovascularization. In the present study, we investigated the effects of modified rice bran hemicellulose (MRBH), a water-soluble hemicellulose preparation from rice bran treated with shiitake enzymes, on vascular endothelial growth factor (VEGF)-induced angiogenesis and its mechanism. We found that MRBH significantly inhibited VEGF-induced tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with human dermal fibroblasts. We also observed that MRBH dose-dependently suppressed the VEGF-induced proliferation and migration of HUVECs. Furthermore, examination of the anti-angiogenic mechanism indicated that MRBH reduced not only VEGF-induced activation of VEGF receptor 2 but also of the downstream signaling proteins Akt, extracellular signal-regulated protein kinase 1/2, and p38 mitogen-activated protein kinase. These findings suggest that MRBH has anti-angiogenic effects that are partially mediated through the inhibition of VEGF signaling.
血管生成与多种病理状况有关，如癌症、类风湿性关节炎、牛皮癣、动脉粥样硬化和视网膜新生血管形成。在本研究中，我们研究了改性米糠半纤维素（MRBH），一种用香菇酶处理过的米糠中的水溶性半纤维素制剂，对血管内皮生长因子（VEGF）诱导的血管生成及其机制的影响。我们发现，MRBH显著抑制了与人类真皮成纤维细胞共培养的人脐静脉内皮细胞（HUVECs）中VEGF诱导的管腔形成。我们还观察到，MRBH剂量依赖性地抑制了VEGF诱导的HUVECs增殖和迁移。此外，对抗血管生成机制的研究表明，MRBH不仅降低了VEGF诱导的VEGF受体2的激活，还降低了下游信号蛋白Akt、细胞外信号调节蛋白激酶1/2和p38丝裂原活化蛋白激酶的激活。这些发现表明，MRBH具有抗血管生成作用，部分是通过抑制VEGF信号传导介导的。
