Eisvand Farhad, Rezvani Kasra, Hosseinzadeh Hossein, Razavi Bibi Marjan
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2024;27(1):90-96. doi: 10.22038/IJBMS.2023.71019.15425.
Diabetes is a chronic disorder that occurs as a result of impaired glucose metabolism. In hyperglycaemic states, the balance between oxidative stress and antioxidant enzymes is disrupted leading to oxidative damage and cell death. In addition, impaired autophagy leads to the storage of dysfunctional proteins and cellular organelles in the cell. Hence, the cytoprotective function of autophagy may be disrupted by high glucose conditions. Alpha-mangostin (A-MG) is an essential xanthone purified from the mangosteen fruit. The different pharmacological benefits of alpha-mangostin, including antioxidant, anti-obesity, and antidiabetic, were demonstrated.
We evaluated the protective influence of A-MG on autophagic response impaired by high concentrations of glucose in human umbilical vein endothelial cells (HUVECs). The HUVECs were treated with various glucose concentrations (5-60 mM) and A-MG (1.25-10 μM) for three days. Then, HUVECs were treated with 60 mM of glucose+2.5 μM of A-MG to measure viability, ROS, and NO content. Finally, the levels of autophagic proteins including LC3, SIRT1, and beclin 1 were evaluated by western blot.
The results expressed that high glucose condition (60 mM) decreased viability and increased ROS and NO content in HUVECs. In addition, LC3, SIRT1, and beclin 1 protein levels declined when HUVECs were exposed to the high concentration of glucose. A-MG reversed these detrimental effects and elevated autophagic protein levels.
Our data represent that A-MG protects HUVECs against high glucose conditions by decreasing ROS and NO generation as well as increasing the expression of autophagy proteins.
糖尿病是一种因葡萄糖代谢受损而发生的慢性疾病。在高血糖状态下，氧化应激与抗氧化酶之间的平衡被打破，导致氧化损伤和细胞死亡。此外，自噬功能受损会导致功能失调的蛋白质和细胞器在细胞内蓄积。因此，自噬的细胞保护功能可能会被高糖环境破坏。α-山竹黄酮（A-MG）是从山竹果中提纯的一种重要的氧杂蒽酮。已证实α-山竹黄酮具有多种药理益处，包括抗氧化、抗肥胖和抗糖尿病作用。
我们评估了A-MG对高浓度葡萄糖损害人脐静脉内皮细胞（HUVECs）自噬反应的保护作用。将HUVECs用不同浓度的葡萄糖（5 - 60 mM）和A-MG（1.25 - 10 μM）处理三天。然后，用60 mM葡萄糖 + 2.5 μM A-MG处理HUVECs以检测细胞活力、活性氧（ROS）和一氧化氮（NO）含量。最后，通过蛋白质印迹法评估包括微管相关蛋白1轻链3（LC3）、沉默信息调节因子1（SIRT1）和贝克林1（beclin 1）在内的自噬蛋白水平。
结果表明，高糖环境（60 mM）降低了HUVECs的活力，增加了ROS和NO含量。此外，当HUVECs暴露于高浓度葡萄糖时，LC3、SIRT1和beclin 1蛋白水平下降。A-MG逆转了这些有害作用并提高了自噬蛋白水平。
我们的数据表明，A-MG通过减少ROS和NO的生成以及增加自噬蛋白的表达来保护HUVECs免受高糖环境的影响。
