Sesamin mitigates inflammation and oxidative stress in endothelial cells exposed to oxidized low-density lipoprotein.
Sesamin, a lignan from sesame oil, has been shown to have antihypertensive and antioxidative properties. This study examined the effects of sesamin on oxidized low-density lipoprotein (oxLDL)-induced endothelial dysfunction. Oxidative stress was determined by measuring the generation of intracellular reactive oxygen species (ROS) and by measuring the expression levels of superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS). To assess the pro-inflammatory effects of oxLDL, ELISA was used to detect IL-8 expression, endothelin-1 (ET-1) secretion, and nuclear factor-kappaB (NF-kappaB) activation. The expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was examined by flow cytometry. In addition, several apoptotic signaling pathways were also investigated. The data showed that sesamin significantly ameliorated oxLDL-induced ROS generation and SOD-1 inactivation. Sesamin also attenuated the oxLDL-induced activation of NF-kappaB, suggesting that the inhibitory effects of sesamin on IL-8 and ET-1 release, adhesion molecule expression, and the adherence of THP-1 cells were at least partially through the blockade of NF-kappaB activation. Furthermore, sesamin attenuated oxLDL-induced apoptotic features, such as intracellular calcium accumulation and the subsequent collapse of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3. Results from this study may provide insight into possible molecular mechanisms underlying sesamin's beneficial effects against oxLDL-mediated vascular endothelial dysfunction.
Lee
Wen-Jane
WJ
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Ou
Hsiu-Chung
HC
Wu
Ching-Mei
CM
Lee
I-Te
IT
Lin
Shih-Yi
SY
Lin
Li-Yun
LY
Tsai
Kun-Ling
KL
Lee
Shin-Da
SD
Sheu
Wayne Huey-Herng
WH
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000276:immunology*; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism
D004149:Dioxoles; D019040:E-Selectin; D017705:Lignans; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C054125:sesamin