Curcumin-induced inhibition of cellular reactive oxygen species generation: Novel therapeutic implications
Curcumin-induced inhibition of cellular reactive oxygen species generation: Novel therapeutic implications
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DOI：
10.1007/bf02708432
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发表时间：
2003-12-01
影响因子：
2.9
通讯作者：
Mohan, V
中科院分区：
文献类型：
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作者：
Balasubramanyam, M;Koteswari, AA;Mohan, V
有证据表明糖尿病患者循环活性氧（ROS）水平升高，这是通过脂质过氧化作用增加和抗氧化状态降低的结果间接推断的。使用荧光染料直接测量细胞内ROS的产生也证明了氧化应激与糖尿病的关联。虽然酚类化合物减弱氧化应激相关的组织损伤，但合成酚类抗氧化剂的毒性引起了人们的关注，这极大地激发了人们对研究天然酚类化合物在医学应用中的作用的兴趣。姜黄素（Curcuma longa Linn.）已被声称是具有植物营养素和生物保护特性的潜在抗氧化剂和杀菌剂。然而，缺乏分子研究来证明其细胞作用和潜在的分子靶点。在这项研究中，姜黄素的抗氧化作用作为细胞ROS产生变化的函数进行了测试。我们的研究结果清楚地表明，姜黄素废除佛波醇-12肉豆蔻酸酯-13乙酸酯（PMA）和毒胡萝卜素诱导的ROS生成的细胞从控制和糖尿病受试者。这些ROS抑制作用的模式作为剂量依赖性的函数表明，姜黄素机械干扰蛋白激酶C（PKC）和钙调节。ROS和Ca 2+内流的同时测量表明，胞质Ca 2+的上升可能是ROS产生增加的触发因素。我们认为，姜黄素的抗氧化和抗血管生成作用，作为一种机制，抑制钙离子内流和PKC活性，应进一步开发合适的和新的药物用于治疗糖尿病视网膜病变和其他糖尿病并发症。
There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.