Abstract
Background:
The hyperglycemic condition in diabetes induces cellular senescence in vascular endothelial cells and causes cardiovascular complications. Alpha-mangostin is a xanthone found in Garcinia mangostana, and has shown protective effects in metabolic syndrome.
Objective:
In this study, the anti-senescence effects of alpha-mangostin in the hyperglycemic condition are investigated.
Methods:
HUVECs were incubated with high glucose for 6 days and co-treated by metformin or alpha-mangostin. After 6 days, cell viability, reactive oxygen species, the percentage of senescent cells, secretory interleukin-6, and the expression of SIRT1, AMPK, p53 and p21 were measured.
Results:
High glucose (60 mM) significantly decreased cellular viability and increased reactive oxygen species and cellular senescence through the reduction of senescence-associated β-galactosidase activity. Moreover, high glucose increased the protein levels of p53, acetyl-p53 and p21. The protein levels of SIRT1 and total AMPK were decreased by high glucose. High glucose increased the secretion of IL-6. Alpha-mangostin (1.25 μM) and metformin (50 μM) reversed the toxic effects of high glucose in HUVECs.
Conclusion:
These results show that alpha-mangostin, similar to metformin, has anti-senescence effects in high-glucose conditions, which is probably due to its antioxidant activity through the SIRT1 pathway. Alpha-mangostin has previously shown anti-inflammatory effects and metabolic status improvement in animal and clinical studies. Therefore, this natural agent can be considered as a supplement to prevent vascular complications caused by high glucose in patients with diabetes. Graphical abstract.
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