Skopinski Piotr, Szaflik Jerzy, Duda-Król Barbara, Nartowska Jadwiga, Sommer Ewa, Chorostowska-Wynimko Joanna, Demkow Urszula, Skopinska-Rózewska Ewa
Second Department of Ophtalmology, Medical University of Warsaw, 13 Sierakowskiego street, 03-709 Warsaw, Poland.
Int J Mol Med. 2004 Oct;14(4):707-11.
Angiogenesis, the process of new blood vessel formation, is the key event in the mechanism of several pathological processes including diabetic retinopathy. The physiological control of angiogenesis depends on the balance between stimulatory and inhibitory factors. Therefore, a number of anti-angiogenic approaches has been developed, many of them based on the inhibition of the functional activity of pro-angiogenic factors. The aim of the present study was to compare the anti-angiogenic effectiveness of sulindac sulfone and some herbal compounds in the serum-induced angiogenesis test performed in Balb/c mice. Pooled sera from 35 patients with diabetes type 2 and retinopathy were used as pro-angiogenic stimuli. The strongest inhibitory effect was observed for the sulindac sulfone and ursolic acid in the highest concentration of 200 micro g/ml, as well as for the low-dosage concomitant treatment with 2 micro g/ml of epigallocatechin gallate (EGCG, green tea flavanol), ursolic acid (plant-derived triterpenoid), sulindac sulfone and convalamaroside (steroidal saponin). Combination treatment was significantly more effective than monotherapy with medium (20 micro g/ml) or lowest doses of tested compounds. The present study is the first to demonstrate the potent anti-angiogenic effect of the combination therapy comprising of plant-derived extracts and sulindac sulfone, as tested in the in vivo angiogenesis experimental model with sera of non-proliferative diabetic retinopathy patients used as the pro-angiogenic stimuli. We think that it might be the first step toward application of some of these compounds, in the future, in preventive anti-angiogenic therapy of these patients, as well, as in the treatment of later, proliferative stage of this disease.
血管生成，即新血管形成的过程，是包括糖尿病视网膜病变在内的多种病理过程机制中的关键事件。血管生成的生理控制取决于刺激因子和抑制因子之间的平衡。因此，已经开发了多种抗血管生成方法，其中许多基于抑制促血管生成因子的功能活性。本研究的目的是在Balb/c小鼠进行的血清诱导血管生成试验中比较舒林酸砜和一些草药化合物的抗血管生成效果。来自35名2型糖尿病和视网膜病变患者的混合血清用作促血管生成刺激物。在200微克/毫升的最高浓度下，观察到舒林酸砜和熊果酸具有最强的抑制作用，同时在低剂量联合治疗中，2微克/毫升的表没食子儿茶素没食子酸酯（EGCG，绿茶黄烷醇）、熊果酸（植物来源的三萜类化合物）、舒林酸砜和康瓦尔苷（甾体皂苷）也有较强抑制作用。联合治疗比用中等剂量（20微克/毫升）或最低剂量的受试化合物进行单一治疗显著更有效。本研究首次证明了在以非增殖性糖尿病视网膜病变患者血清作为促血管生成刺激物的体内血管生成实验模型中，植物提取物与舒林酸砜联合治疗具有强大的抗血管生成作用。我们认为，这可能是未来将其中一些化合物应用于这些患者的预防性抗血管生成治疗以及该疾病后期增殖期治疗的第一步。
