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Alpha-mangostin decreased cellular senescence in human umbilical vein endothelial cells
Hourieh Tousian1, Bibi Marjan Razavi1,2, Hossein Hosseinzadeh3,4
1Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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.
Insights
Alpha-mangostin, a natural compound, combats high glucose-induced cellular senescence in blood vessel cells. This suggests its potential as a supplement to prevent diabetes-related vascular complications.
Area of Science:
- Biomedical Science
- Cell Biology
- Endocrinology
Background:
- Diabetes-induced hyperglycemia accelerates vascular endothelial cell senescence, contributing to cardiovascular disease.
- Alpha-mangostin, a xanthone from Garcinia mangostana, exhibits protective effects in metabolic syndrome.
Purpose of the Study:
- To investigate the anti-senescence properties of alpha-mangostin under hyperglycemic conditions.
- To evaluate alpha-mangostin's impact on cellular senescence markers and related pathways.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (60 mM) for six days.
- Cells were co-treated with alpha-mangostin (1.25 μM) or metformin (50 μM).
- Measurements included cell viability, reactive oxygen species (ROS), senescence percentage, IL-6 secretion, and expression of SIRT1, AMPK, p53, and p21.
Main Results:
- High glucose reduced cell viability, increased ROS and senescence (β-galactosidase activity), and elevated p53, acetyl-p53, and p21 levels.
- High glucose decreased SIRT1 and AMPK protein levels and increased IL-6 secretion.
- Alpha-mangostin and metformin counteracted the detrimental effects of high glucose on HUVECs.
Conclusions:
- Alpha-mangostin demonstrates anti-senescence effects in high-glucose conditions, comparable to metformin.
- These effects are likely mediated by antioxidant activity via the SIRT1 pathway.
- Alpha-mangostin may serve as a valuable supplement for preventing diabetic vascular complications.
