首页> 外文期刊>Free Radical Biology and Medicine: The Official Journal of the Oxygen Society >Isolation, identification, and biological evaluation of Nrf2-ARE activator from the leaves of green perilla (Perilla frutescens var. crispa f. viridis)
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Isolation, identification, and biological evaluation of Nrf2-ARE activator from the leaves of green perilla (Perilla frutescens var. crispa f. viridis)

机译:绿紫苏(Perilla frutescens var。crispa f。viridis)叶片中Nrf2-ARE激活剂的分离,鉴定和生物学评估

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摘要

The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is a cellular defense system against oxidative stress. Activation of this pathway increases expression of antioxidant enzymes. Epidemiological studies have demonstrated that the consumption of fruits and vegetables is associated with reduced risk of contracting a variety of human diseases. The aim of this study is to find Nrf2-ARE activators in dietary fruits and vegetables. We first attempted to compare the potency of ARE activation in six fruit and six vegetables extracts. Green perilla (Perilla frutescens var. crispa f. viridis) extract exhibited high ARE activity. We isolated the active fraction from green perilla extract through bioactivity-guided fractionation. Based on nuclear magnetic resonance and mass spectrometric analysis, the active ingredient responsible for the ARE activity was identified as 2′,3′-dihydroxy-4′,6′-dimethoxychalcone (DDC). DDC induced the expression of antioxidant enzymes, such as γ-glutamylcysteine synthetase (γ-GCS), NAD(P)H: quinone oxidoreductase-1 (NQO1), and heme oxygenase-1. DDC inhibited the formation of intracellular reactive oxygen species and the cytotoxicity induced by 6-hydroxydopamine. Inhibition of the p38 mitogen-activated protein kinase pathway abolished ARE activation, the induction of γ-GCS and NQO1, and the cytoprotective effect brought about by DDC. Thus, this study demonstrated that DDC contained in green perilla enhanced cellular resistance to oxidative damage through activation of the Nrf2-ARE pathway.
机译:核因子红系2相关因子2(Nrf2)-抗氧化反应元件(ARE)途径是针对氧化应激的细胞防御系统。该途径的激活增加了抗氧化酶的表达。流行病学研究表明,食用水果和蔬菜与减少感染多种人类疾病的风险有关。这项研究的目的是在饮食水果和蔬菜中找到Nrf2-ARE激活剂。我们首先尝试比较六种水果和六种蔬菜提取物中ARE活化的效力。绿紫苏(Perilla frutescens var。crispa f。viridis)提取物表现出较高的ARE活性。我们通过生物活性指导的分离从绿色紫苏提取物中分离出了活性组分。基于核磁共振和质谱分析,将负责ARE活性的活性成分鉴定为2',3'-二羟基-4',6'-二甲氧基查尔酮(DDC)。 DDC诱导抗氧化剂酶的表达,例如γ-谷氨酰半胱氨酸合成酶(γ-GCS),NAD(P)H:醌氧化还原酶-1(NQO1)和血红素加氧酶-1。 DDC抑制了细胞内活性氧的形成和6-羟基多巴胺诱导的细胞毒性。抑制p38丝裂原活化的蛋白激酶途径消除了ARE活化,γ-GCS和NQO1的诱导以及DDC带来的细胞保护作用。因此,这项研究表明,绿色紫苏中所含的DDC通过激活Nrf2-ARE途径增强了细胞对氧化损伤的抵抗力。

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