Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
J Agric Food Chem. 2012 Feb 22;60(7):1666-72. doi: 10.1021/jf204327c. Epub 2012 Feb 8.
Previous studies have established that red mold rice can regulate blood pressure in spontaneously hypertensive rats (SHR) and that Monascus -fermented products, including monacolin K, ankaflavin (AF), and monascin (MS), can inhibit expression of adhesion factors such as E-selectin and endothelin-1 to prevent human acute monocytic leukemia cell line THP-1 monocytes from adhering to human aortic endothelial cells. However, it remains unknown whether AF and MS act directly on human umbilical endothelial cells (HUVECs) to enhance nitric oxide (NO) synthesis through the stimulation of endothelial NO synthase (eNOS) expression. To address this knowledge gap, this study investigated whether AF and MS directly regulate NO synthesis and attenuate adhesion factor expression induced by treatment with tumor necrosis factor-α (TNF-α) in HUVECs. The results revealed that both AF and MS (20 μM) treatments promoted increases in eNOS expression and decreases in vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and endothelin-1 mRNA and protein expression resulting from 12 h of TNF-α treatment. These effects are attributed to the ability of AF and MS to inhibit extracellular signal-regulated protein kinase (ERK) phosphorylation and nuclear factor κB (NF-κB) translocation from the cytoplasm into the nucleus, thereby exerting antihypertensive activity.
先前的研究已经证实，红曲霉米可以调节自发性高血压大鼠（SHR）的血压，而红曲霉发酵产物，包括洛伐他汀（Monacolin K）、安卡黄素（ankaflavin，AF）和红曲素（monascin，MS），可以抑制粘附因子如 E-选择素和内皮素-1 的表达，从而防止人类急性单核细胞白血病细胞系 THP-1 单核细胞黏附于人主动脉内皮细胞。然而，目前尚不清楚 AF 和 MS 是否直接作用于人脐静脉内皮细胞（HUVEC），通过刺激内皮型一氧化氮合酶（endothelial nitric oxide synthase，eNOS）的表达来增强一氧化氮（nitric oxide，NO）的合成。为了填补这一知识空白，本研究旨在探讨 AF 和 MS 是否直接调节 NO 合成，并减轻 TNF-α处理诱导的 HUVEC 中粘附因子的表达。结果表明，AF 和 MS（20 μM）处理均可促进 eNOS 表达的增加，以及 TNF-α处理 12 小时后血管细胞粘附分子-1（vascular cell adhesion molecule-1，VCAM-1）、E-选择素和内皮素-1 mRNA 和蛋白表达的减少。这些作用归因于 AF 和 MS 抑制细胞外信号调节蛋白激酶（extracellular signal-regulated protein kinase，ERK）磷酸化和核因子 κB（nuclear factor κB，NF-κB）从细胞质向细胞核易位的能力，从而发挥降压作用。
