Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; CSIR-Central Food Technological Research Institute, Mysore, Karnataka, 570020, India.
CSIR-Central Food Technological Research Institute, Mysore, Karnataka, 570020, India.
Eur J Pharmacol. 2021 May 15;899:174014. doi: 10.1016/j.ejphar.2021.174014. Epub 2021 Mar 8.
Hyperglycemia mediated perturbations in biochemical pathways induce angiogenesis in diabetic retinopathy (DR) pathogenesis. The present study aimed to investigate the protective effects of lactucaxanthin, a predominant lettuce carotenoid, on hyperglycemia-mediated activation of angiogenesis in vitro and in vivo diabetic model. ARPE-19 cells cultured in 30 mM glucose concentration were treated with lactucaxanthin (5 μM and 10 μM) for 48 h. They were assessed for antioxidant enzyme activity, mitochondrial membrane potential, reactive oxygen species, and cell migration. In the animal experiment, streptozotocin-induced diabetic male Wistar rats were gavaged with lactucaxanthin (200 μM) for 8 weeks. Parameters like animal weight gain, feed intake, water intake, urine output, and fasting blood glucose level were monitored. In both models, lutein-treated groups were considered as a positive control. Hyperglycemia-mediated angiogenic marker expressions in ARPE-19 and retina of diabetic rats were quantified through the western blot technique. Expression of hypoxia, endoplasmic reticulum stress markers, and vascular endothelial growth factor were found to be augmented in the hyperglycemia group compared to control (P < 0.05). Hyperglycemia plays a crucial role in increasing cellular migration and reactive oxygen species besides disrupting tight junction protein. Compared to lutein, lactucaxanthin aids retinal pigment epithelium (RPE) function from hyperglycemia-induced stress conditions via downregulating angiogenesis markers expression. Lactucaxanthin potentiality observed in protecting tight junction protein expression via modulating reactive oxygen species found to conserve RPE integrity. Results demonstrate that lactucaxanthin exhibits robust anti-angiogenic activity for the first time and, therefore, would be useful as an alternative therapy to prevent or delay DR progression.
高血糖介导的生化途径改变诱导糖尿病视网膜病变 (DR) 发病中的血管生成。本研究旨在探讨生菜叶黄素，一种主要的生菜类胡萝卜素，对体外和体内糖尿病模型中高血糖介导的血管生成激活的保护作用。将 ARPE-19 细胞在 30mM 葡萄糖浓度下培养，并分别用生菜叶黄素（5μM 和 10μM）处理 48 小时。评估抗氧化酶活性、线粒体膜电位、活性氧和细胞迁移。在动物实验中，链脲佐菌素诱导的糖尿病雄性 Wistar 大鼠用生菜叶黄素（200μM）灌胃 8 周。监测动物体重增加、饲料摄入量、水摄入量、尿量和空腹血糖水平等参数。在这两种模型中，叶黄素处理组被认为是阳性对照。通过 Western blot 技术定量测定 ARPE-19 和糖尿病大鼠视网膜中高血糖介导的血管生成标记物的表达。与对照组相比，高血糖组中缺氧、内质网应激标志物和血管内皮生长因子的表达增加（P<0.05）。与叶黄素相比，生菜叶黄素通过下调血管生成标记物的表达，有助于从高血糖引起的应激条件下保护视网膜色素上皮（RPE）功能。观察到生菜叶黄素通过调节活性氧来保护紧密连接蛋白表达的潜力，从而发现其具有保护 RPE 完整性的潜力。结果表明，生菜叶黄素首次表现出强大的抗血管生成活性，因此可作为预防或延迟 DR 进展的替代治疗方法。
