Farhad Eisvand - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Kasra Rezvani - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Hossein Hosseinzadeh - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Bibi Marjan Razavi - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): 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. Materials and Methods: 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 (۵-۶۰ mM) and A-MG (۱.۲۵-۱۰ μM) for three days. Then, HUVECs were treated with ۶۰ mM of glucose+۲.۵ μM of A-MG to measure viability, ROS, and NO content. Finally, the levels of autophagic proteins including LC۳, SIRT۱, and beclin ۱ were evaluated by western blot.Results: The results expressed that high glucose condition (۶۰ mM) decreased viability and increased ROS and NO content in HUVECs. In addition, LC۳, SIRT۱, and beclin ۱ protein levels declined when HUVECs were exposed to the high concentration of glucose. A-MG reversed these detrimental effects and elevated autophagic protein levels.Conclusion: 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.

Alpha-mangostin, Autophagy, Beclin ۱, Diabetes, Garcinia mangostana, HUVEC, LC۳, SIRT۱