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γ-Oryzanol Ameliorates Endothelial Replicative Senescence via Downregulation of SGLT2 Expression to Attenuate
Saugat Shiwakoti1, Kushal Sharma1, Dal-Seong Gong1
1College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea.
Abstract:
Replicative senescence in endothelial cells is characterized by an irreversible cell cycle arrest and impaired endothelial function, contributing to vascular aging and cardiovascular disease. Natural compounds are being actively studied for their potential to delay cellular senescence and protect vascular health. Among them, rice bran has demonstrated several vascular benefits that are mainly attributed to gamma-oryzanol (γ-Orz), a major bioactive component in rice bran. However, its role in regulating endothelial replicative senescence and the underlying molecular mechanisms remain unclear. This study aimed to explore the protective effects of rice bran extract (RBE) and γ-Orz on replicative senescence in porcine coronary artery endothelial cells (PCAECs). Replicative senescence was modeled in PCAECs by serial passaging from P1 to P3 with varying concentrations of RBE and γ-Orz. Senescence was evaluated by measuring senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, oxidative stress, and the expression of cell cycle regulatory proteins. RBE and γ-Orz significantly reduced SA-β-gal activity, improved proliferation, and decreased oxidative stress in P3 cells, along with downregulation of senescence-related proteins p53, p21, and p16. Additionally, γ-Orz suppressed sodium-glucose co-transporter 2 expression, reduced NADPH oxidase overexpression, and restored eNOS levels. These findings indicate that RBE and γ-Orz delay endothelial senescence by alleviating oxidative stress, highlighting their potential to reduce cardiovascular disease risk associated with endothelial senescence.
Insights
Rice bran extract and gamma-oryzanol delay endothelial cell senescence, reducing oxidative stress and improving vascular health. These natural compounds show promise in mitigating cardiovascular disease risk linked to aging blood vessels.
Area of Science:
- Vascular Biology
- Cellular Senescence
- Nutraceuticals
Background:
- Endothelial replicative senescence contributes to vascular aging and cardiovascular disease.
- Natural compounds, like gamma-oryzanol from rice bran, are investigated for vascular protection.
- The specific role of gamma-oryzanol in endothelial senescence is not well understood.
Purpose of the Study:
- To investigate the protective effects of rice bran extract (RBE) and gamma-oryzanol (γ-Orz) on replicative senescence in porcine coronary artery endothelial cells (PCAECs).
- To elucidate the molecular mechanisms underlying the anti-senescence effects of RBE and γ-Orz.
Main Methods:
- Replicative senescence was induced in PCAECs through serial passaging.
- Cells were treated with varying concentrations of RBE and γ-Orz.
- Senescence markers including SA-β-gal activity, proliferation, oxidative stress, and cell cycle proteins (p53, p21, p16) were assessed.
Main Results:
- RBE and γ-Orz significantly reduced SA-β-gal activity and improved cell proliferation in senescent PCAECs.
- Treatment decreased oxidative stress markers and downregulated key senescence-related proteins (p53, p21, p16).
- γ-Orz modulated sodium-glucose co-transporter 2, NADPH oxidase, and eNOS expression.
Conclusions:
- Rice bran extract and gamma-oryzanol effectively delay endothelial replicative senescence.
- These compounds alleviate endothelial oxidative stress, a key factor in senescence.
- RBE and γ-Orz hold potential for reducing cardiovascular disease risk associated with endothelial aging.
