Sen Serkan, Kasikci Murat
Department of Medical Laboratory Techniques, Ataturk Vocational School of Health Services, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey.
Department of Ophthalmology, Muğla Training and Research Hospital, Mugla, Turkey.
J Cell Mol Med. 2025 Jan;29(1):e70327. doi: 10.1111/jcmm.70327.
Nowadays, the use of monoclonal antibodies to target angiogenic signalling pathways is common, but, unfortunately, the clinical activity of these agents is limited. Thus, the development of approaches targeting multiple pathways for anti-angiogenic effect will lead to increase the clinical benefit. For this purpose, oleuropein, hesperidin, piperine, proanthocyanidins and retinoic acid, which have previously been proven to be bioactive components, anti-angiogenic performances were experimentally tested in retinal pigment epithelial cells. Bioactive ingredients were applied to retinal pigment epithelial cells at varying doses for 48 h, and then IC doses were calculated by MTT analysis. VEGFA and VEGFR1 protein levels were measured by ELISA analysis. Using the RT-PCR technique, the mRNA expression levels of EGF, EGFR, PDGF, PDGFR-β and HIF1A were analysed. Among all bioactive compounds, the bevacizumab group showed the best anti-VEGF activity, followed by the proanthocyanidins and piperine groups. Piperine group showed EGF, PDGF and HIF1A expressions; proanthocyanidins, on the other hand, reduced EGFR, PDGF and HIF1A expressions. Retinoic acid showed an angiogenic effect by increasing VEGFA protein levels and EGF and PDGFR-β expressions. Although hesperidin increased VEGFA protein levels, it decreased EGF, PDGF, PFGFR-β and HIF1A expression levels. Among the bioactive components stated in previous studies to have anti-angiogenic properties, only proanthocyanidins and piperin had anti-VEGF properties. Considering that angiogenesis does not proceed only through VEGF, this study investigated and reported for the first time the effects of relevant bioactive components on angiogenesis through different mechanisms in retinal pigment epithelial cells.
如今，使用单克隆抗体靶向血管生成信号通路很常见，但遗憾的是，这些药物的临床活性有限。因此，开发针对多种通路以产生抗血管生成作用的方法将提高临床获益。为此，在视网膜色素上皮细胞中对橄榄苦苷、橙皮苷、胡椒碱、原花青素和视黄酸进行了实验测试，这些物质先前已被证明是生物活性成分，具有抗血管生成性能。将生物活性成分以不同剂量应用于视网膜色素上皮细胞48小时，然后通过MTT分析计算IC剂量。通过ELISA分析测量VEGFA和VEGFR1蛋白水平。使用RT-PCR技术分析EGF、EGFR、PDGF、PDGFR-β和HIF1A的mRNA表达水平。在所有生物活性化合物中，贝伐单抗组显示出最佳的抗VEGF活性，其次是原花青素和胡椒碱组。胡椒碱组显示出EGF、PDGF和HIF1A的表达；另一方面，原花青素降低了EGFR、PDGF和HIF1A的表达。视黄酸通过增加VEGFA蛋白水平以及EGF和PDGFR-β的表达显示出血管生成作用。尽管橙皮苷增加了VEGFA蛋白水平，但它降低了EGF、PDGF、PFGFR-β和HIF1A的表达水平。在先前研究中表明具有抗血管生成特性的生物活性成分中，只有原花青素和胡椒碱具有抗VEGF特性。鉴于血管生成并非仅通过VEGF进行，本研究首次调查并报告了相关生物活性成分在视网膜色素上皮细胞中通过不同机制对血管生成的影响。
