Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase
Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase
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DOI：
10.1007/s11357-009-9124-1
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发表时间：
2010-06-01
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影响因子：
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通讯作者：
Chung, Hae Young
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作者：
Kim, Ji Min;Lee, Eun Kyeong;Chung, Hae Young
晚期糖基化终产物（AGE）是由碳水化合物与活性物质（RS）激发的游离氨基蛋白质之间的反应形成的氧化产物。我们还知道AGE可促进RS的生成，AGE与特定AGE受体（RAGE）的结合可诱导氧化还原敏感的促炎转录因子核因子- κ B （NF-AB）的激活。在本研究中，我们研究了短期补充山奈酚对老年大鼠肾脏年龄相关性AGE形成和RAGE结合活性的抗氧化作用。我们进一步研究山奈酚对AGE刺激促炎NF-AB活化能力的抑制作用及其分子机制。在这项研究中，我们使用幼龄大鼠（6个月大）、老年大鼠（24个月大）和山奈酚喂养大鼠（2和4 mg/kg/天，持续10天）。此外，分子工作采用大鼠内皮细胞系pen -1。结果表明，衰老过程中AGE和RAGE均呈升高趋势，山奈酚可抑制AGE和RAGE的升高。此外，饮食山奈酚降低了nf - κ B活性和nf - ab依赖性促炎基因活性的年龄相关性增加。本研究最重要的新发现是山奈酚补充剂通过抑制年龄诱导的烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶）来阻止年龄相关的nf - κ B活化。综上所述，我们的研究结果表明，饮食山奈酚通过抑制年龄诱导的NADPH氧化酶激活，调节与年龄相关的nf - κ B信号级联及其促炎基因，发挥其抗氧化和抗炎作用。基于这些数据，膳食山奈酚被认为是一种可能的抗age药物，可能在抗炎症治疗中有潜在的用途。
Advanced glycation endproducts (AGE) are oxidative products formed from the reaction between carbohydrates and a free amino group of proteins that are provoked by reactive species (RS). It is also known that AGE enhance the generation of RS and that the binding of AGE to a specific AGE receptor (RAGE) induces the activation of the redox-sensitive, pro-inflammatory transcription factor, nuclear factor-kappa B (NF-AB). In this current study, we investigated the anti-oxidative effects of short-term kaempferol supplementation on the age-related formation of AGE and the binding activity of RAGE in aged rat kidney. We further investigated the suppressive action of kaempferol against AGE's ability to stimulate activation of pro-inflammatory NF-AB and its molecular mechanisms. For this study, we utilized young (6 months old), old (24 months old), and kaempferol-fed (2 and 4 mg/kg/day for 10 days) old rats. In addition, for the molecular work, the rat endothelial cell line, YPEN-1 was used. The results show that AGE and RAGE were increased during aging and that these increases were blunted by kaempferol. In addition, dietary kaempferol reduced age-related increases in NF-kappa B activity and NF-AB-dependant pro-inflammatory gene activity. The most significant new finding from this study is that kaempferol supplementation prevented age-related NF-kappa B activation by suppressing AGE-induced nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Taken together, our results demonstrated that dietary kaempferol exerts its anti-oxidative and anti-inflammatory actions by modulating the age-related NF-kappa B signaling cascade and its pro-inflammatory genes by suppressing AGE-induced NADPH oxidase activation. Based on these data, dietary kaempferol is proposed as a possible anti-AGE agent that may have the potential for use in anti-inflammation therapies.