Elucidation of mechanism on "French Paradox" toward prevention of lifestyle-related diseases

在野生型而非PPARα敲除小鼠中，乳制品中摄入白藜芦醇（红酒中含有的一种植物抗毒素）可降低血浆甘油三酯浓度，并上调肝脏中PPAR-α应答基因的表达。此外，在高脂饮食中长期摄入0.02%白藜芦醇，可防止小鼠46周后体重增加和腹部白色脂肪组织的积累，提高小鼠存活率。这些发现将解释一种可能对预防生活方式相关疾病产生有益影响的新机制。一些天然化学物质如白藜芦醇已被确定为COX-2表达的抑制因子和PPARs的激活因子。这两个针对COX-2和PPARs的特性将有助于评估功能性食品成分对生活方式相关疾病的影响。在这种情况下，我们在细胞转染实验中评估了来自各种植物的精油，发现百里香、玫瑰、丁香、茴香、桉树和佛手柑中的六种精油具有这些特性。从百里香油中，我们发现香芹酚是PPARα和γ激活剂以及COX-2表达抑制剂的主要成分，并且在香芹酚处理下，ppar γ依赖性的COX-2启动子活性受到抑制。这些结果将对了解精油的抗生活方式相关疾病特性具有重要意义。

Dairy oral intake of resveratrol, a phytoalexin contained in red wine, reduces plasma triglyceride concentration, and upregulates hepatic expression of PPAR-α responsive genes in the wild-type but not PPARα knockout mice. Moreover, long-term intake of 0.02% resveratrol with high fat diet prevents body weight gain observed after 46 weeks and accumulation of abdominal white adipose tissue, and improves survival of mice. These findings will account for a novel mechanism that may afford beneficial effects of preventing lifestyle-related diseases.Several natural chemicals such as resveratrol have been identified as suppressors of COX-2 expression and activators of PPARs. These two properties targeted to COX-2 and PPARs will be useful in evaluating functional food components against lifestyle-related diseases. In this context, we evaluated oils from various plants in cell-based transfection assays, and found that six essential oils from thyme, rose, clove, fennel, eucalyptus, and bergamot, have these properties. From thyme oil, we identified carvacrol as a major component of the activator of PPARα and γ and suppressor of COX-2 expression, and PPARγ-dependent suppression of COX-2 promoter activity was observed in response to carvacrol treatment. These results will be important in understanding the anti-lifestyle-related disease properties of essential oils.