Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM and Engineering & Technology Research Center for Chinese Materia Medica Quality of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou, 510632, China.
Food Chem Toxicol. 2021 Jul;153:112244. doi: 10.1016/j.fct.2021.112244. Epub 2021 Apr 27.
Methylglyoxal (MGO), a cytotoxic byproduct of glycolysis in biological systems, can induce endothelial cells dysfunction, implicated in diabetic vascular complications. Pterostilbene (PTS), a naturally occurring resveratrol derivative, is involved in various pharmacological activities. This study aimed to explore the effects of PTS on MGO induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms for the first time. In the current study, it has been demonstrated that PTS could enhance the level of glyoxalase 1 (GLO-1) and elevate glutathione (GSH) content to active the glyoxalase system, resulting in elimination of the toxic MGO as well as advanced glycation end products (AGEs) in HUVECs. Meanwhile, PTS could also suppress oxidative stress and thus exert cytoprotective effects by elevating Nrf2 nuclear translocation and the corresponding down-stream antioxidant enzymes in MGO induced HUVECs. In addition, PTS could alleviate MGO induced apoptosis in HUVECs via inhibition of oxidative stress and associated downstream mitochondria-dependent signaling apoptotic cascades, as characterized by preventing caspases family activation. Taken together, these findings suggest that PTS could protect against MGO induced endothelial cell cytotoxicity by regulating glyoxalase, oxidative stress and apoptosis, suggesting that PTS could be beneficial in the treatment of diabetic vascular complications.
甲基乙二醛（MGO）是生物体系糖酵解过程中的一种细胞毒性副产物，可诱导内皮细胞功能障碍，与糖尿病血管并发症有关。紫檀芪（PTS）是一种天然存在的白藜芦醇衍生物，具有多种药理活性。本研究首次旨在探讨紫檀芪对人脐静脉内皮细胞（HUVEC）中 MGO 诱导的细胞毒性的影响及其潜在机制。在本研究中，已经证明 PTS 可以增强糖氧还蛋白 1（GLO-1）的水平并提高谷胱甘肽（GSH）含量，从而激活糖氧还系统，消除 HUVEC 中的有毒 MGO 以及晚期糖基化终产物（AGEs）。同时，PTS 还可以通过增加 Nrf2 核易位和相应的下游抗氧化酶来抑制氧化应激，从而在 MGO 诱导的 HUVEC 中发挥细胞保护作用。此外，PTS 可以通过抑制氧化应激和相关的下游线粒体依赖性信号凋亡级联反应来减轻 MGO 诱导的 HUVEC 凋亡，表现为阻止半胱天冬酶家族的激活。总之，这些发现表明，PTS 通过调节糖氧还酶、氧化应激和凋亡来保护内皮细胞免受 MGO 诱导的细胞毒性，这表明 PTS 可能有益于治疗糖尿病血管并发症。
