Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Biochem Pharmacol. 2018 Jun;152:1-10. doi: 10.1016/j.bcp.2018.03.012. Epub 2018 Mar 14.
Although didymin, a flavonoid-O-glycosides compound naturally found in the citrus fruits, has been reported to be a potent anticancer agent in the prevention of various cancers, its role in the prevention of cardiovascular complications is unclear. Most importantly, its effect in the prevention of endothelial dysfunction, a pathological process involved in the atherogenesis, is unknown. We have examined the efficacy of didymin in preventing the high glucose (HG; 25 mM)-induced human umbilical vein endothelial cells (HUVECs) dysfunction. Our results indicate that incubation of HUVECs with HG resulted in the loss of cell viability, and pre-incubation of didymin prevented it. Further, didymin prevented the HG-induced generation of reactive oxygen species (ROS) as well as lipid peroxidation product, malondialdehyde. Pretreatment of HUVECs with didymin also prevented the HG-induced decrease in eNOS and increase in iNOS expressions. Further, didymin prevented the HG-induced monocytes cell adhesion to endothelial cells, expressions of ICAM-1 and VCAM-1 and activation of NF-κB. Didymin also prevented the release of various inflammatory cytokines and chemokines in HG-treated HUVECs. In conclusion, our results demonstrate that didymin with its anti-oxidative and anti-inflammatory actions prevents hyperglycemia-induced endothelial dysfunction and death. Thus, it could be developed as a potential natural therapeutic agent for the prevention of cardiovascular complications in diabetes.
尽管二氢杨梅素是一种天然存在于柑橘类水果中的类黄酮-O-糖苷化合物，已被报道具有预防多种癌症的强大抗癌作用，但它在预防心血管并发症方面的作用尚不清楚。最重要的是，其预防内皮功能障碍的效果（动脉粥样硬化形成过程中的一个病理过程）尚不清楚。我们已经研究了二氢杨梅素预防高葡萄糖（HG；25mM）诱导的人脐静脉内皮细胞（HUVEC）功能障碍的功效。我们的结果表明，HG 孵育 HUVEC 会导致细胞活力丧失，而二氢杨梅素的预孵育可预防这种情况。此外，二氢杨梅素可预防 HG 诱导的活性氧（ROS）和脂质过氧化产物丙二醛的产生。用二氢杨梅素预处理 HUVEC 还可预防 HG 诱导的 eNOS 表达降低和 iNOS 表达增加。此外，二氢杨梅素可预防 HG 诱导的单核细胞黏附内皮细胞、ICAM-1 和 VCAM-1 的表达以及 NF-κB 的激活。二氢杨梅素还可预防 HG 处理的 HUVEC 中各种炎症细胞因子和趋化因子的释放。总之，我们的结果表明，二氢杨梅素具有抗氧化和抗炎作用，可预防高血糖引起的内皮功能障碍和死亡。因此，它可能被开发为预防糖尿病心血管并发症的潜在天然治疗剂。
