Abstract 356: Rice Bran Extracts and Its Active Compound, γ-oryzanol, Prevent Particulate Matters-induced Endothelium Senescence

Abstract

Particulate matters (PMs) derived from are known to be responsible for a wide range of diseases. Recent studies have indicated that long-term exposure PMs is associated with several cardiovascular diseases, at least in part, by increase of inflammation, oxidative stress and nitric oxide (NO) balance disturbance. The present study was to investigate the protective effect of rice bran and its active compound, γ-oryzanol (γ-Orz), on PMs-induced premature endothelial senescence, and if then, to explore the underlying mechanism. Premature senescence was induced in porcine coronary arterial endothelial cells (PCAECs) by incubating 30 μg/mL of PM10. Senescence-associated β-galactosidase (SA-β-gal) activity, oxidative stress, expression level of cell cycle regulatory proteins, nicotinamide adenine dinucleotide phosphate(NADPH) oxidase, and local angiotensin system (LAS) component were evaluated. The result showed that senescence associated-β-gal activity in the PMs-treated PCAECs was attenuated by rice bran extracts (RBEs) and its major constituent, γ-Orz. Pretreatment with γ-Orz inhibited PMs-induced oxidative stress in PCAECs. Similarly, γ-Orz restored the cell proliferation of PCAECs by inhibiting PMs -induced cell cycle arrest. Western blot analyses revealed that cell cycle regulatory protein such as p53, p16, and p21 in senescent PCAECs treated with γ-Orz were reduced from PMs-exposed cells. In addition, γ- Orz prevented senescence associated NADPH oxidase, LAS activity of PM10-exposed cells. Pretreatment of γ-Orz restored PM10-induced endothelial dysfunction by upregulation of endothelial NO synthase expression. The present study demonstrated that γ-Orz protects against PMs induced PCAECs senescence, potentially through abrogating oxidative stress pathway. Taken together, this study can serve as a pharmacological use of rice bran extracts and γ-Orz for the prevention and/or treatment of air pollution-associated coronary artery diseases.