Lee Yun Mi, Lee Yu-Ri, Kim Chan-Sik, Jo Kyuhyung, Sohn Eunjin, Kim Jin Sook, Kim Junghyun
Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea.
Department of Biology, Chungnam National University, Daejeon, 34134, South Korea.
BMC Complement Altern Med. 2016 Jul 19;16:231. doi: 10.1186/s12906-016-1216-8.
Retinal neovascularization, which is the pathological growth of new blood vessels, is associated with retinopathy of prematurity, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. In this study, we evaluated the effect of an extract of Cnidium officinale Makino (COE) and its bioactive compound, butylidenephthalide (BP), on the migration and tube formation of human umbilical vein endothelial cells (HUVECs), and on retinal pathogenic neovascularization in the oxygen-induced retinopathy (OIR) mouse model.
The HUVECs were incubated with COE and BP (0.1-10 μg/ml). The mice were exposed to 75 % oxygen for 5 days starting on the 7(th) postnatal day (P7-P12). Then, the mice were returned to room air and intraperitoneally injected with COE (100 mg/kg) and BP (5 mg/kg) once per day for 5 days (P12-P16). On P17, we measured retinal neovascularization and analyzed the angiogenesis-related proteins expression using protein arrays.
COE and BP inhibit the HUVECs migration and the tube formation in a dose-dependent manner. In addition, COE significantly decreased retinal neovascularization in the OIR mice. COE reduced the expression levels of AREG, ANG, DLL4, Endostatin, IGFBP-2 and VEGF. Additionally, BP also inhibited the retinal neovascularization and down-regulated the expression of AREG, ANG, DLL4 and VEGF.
These results suggest that COE and BP exerts antiangiogenic effects on retinal neovascularization by inhibiting the expression of AREG, ANG, DLL4 and VEGF, indicating that antiangiogenic activities of COE may be in part due to its bioactive compound, BP.
视网膜新生血管形成是新血管的病理性生长，与早产儿视网膜病变、新生血管性年龄相关性黄斑变性、糖尿病视网膜病变及视网膜静脉阻塞相关。在本研究中，我们评估了蛇床子提取物（COE）及其生物活性化合物丁烯基苯酞（BP）对人脐静脉内皮细胞（HUVECs）迁移和管腔形成的影响，以及对氧诱导视网膜病变（OIR）小鼠模型中视网膜病理性新生血管形成的影响。
将HUVECs与COE和BP（0.1 - 10μg/ml）一起孵育。小鼠在出生后第7天（P7 - P12）开始暴露于75%氧气中5天。然后，将小鼠放回正常空气中，并每天腹腔注射COE（100mg/kg）和BP（5mg/kg），持续5天（P12 - P16）。在P17时，我们测量视网膜新生血管形成，并使用蛋白质芯片分析血管生成相关蛋白的表达。
COE和BP以剂量依赖性方式抑制HUVECs迁移和管腔形成。此外，COE显著降低了OIR小鼠的视网膜新生血管形成。COE降低了AREG、ANG、DLL4、内皮抑素、IGFBP - 2和VEGF的表达水平。此外，BP也抑制了视网膜新生血管形成，并下调了AREG、ANG、DLL4和VEGF的表达。
这些结果表明，COE和BP通过抑制AREG、ANG、DLL4和VEGF的表达对视网膜新生血管形成发挥抗血管生成作用，表明COE的抗血管生成活性可能部分归因于其生物活性化合物BP。
