Christian Doppler Laboratory for Receptor Biotechnology, Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Vienna, Austria.
Menopause. 2010 Mar;17(2):379-87. doi: 10.1097/gme.0b013e3181c94617.
Inflammation and hyperlipidemia or dyslipidemia contribute to an increased risk of atherosclerosis and cardiovascular disease. Cardiovascular disease represents one of the major causes of premature death worldwide. The activation of peroxisome proliferator-activated receptor (PPAR) alpha, a drug target for hyperlipidemia and dyslipidemia, leads to an improved blood lipid profile. In this study, we determined the putative anti-inflammatory and PPARalpha stimulatory activities of red clover, an alternative to the classic hormone therapy used currently to treat menopausal symptoms.
Lipopolysaccharide-induced macrophages were used as a model for anti-inflammatory activity, and a chimeric GAL4-PPARalpha system was used as a model for putative hypolipidemic activity.
Red clover extract and the isoflavones genistein and biochanin A were moderate PPARalpha activators. Daidzein only slightly activated PPARalpha, but its metabolite 6-hydroxydaidzein exerted a much higher PPARalpha activity. Similarly, the metabolite 3'-hydroxygenistein achieved higher activation efficiency than its precursor, genistein, did. In lipopolysaccharide-stimulated macrophages, red clover extract and its compounds reduced the secretion of proinflammatory cytokines, interleukin-6 and tumor necrosis factor alpha, increased the secretion of the anti-inflammatory interleukin-10, and/or reduced the expression of nuclear factor-kappaB, inducible nitric oxide synthase, and/or cyclooxygenase 2. Tumor necrosis factor alpha production was most efficiently reduced by biochanin A and genistein. Interleukin-6 levels were most efficiently reduced by genistein and equol.
Owing to its PPARalpha activation and modulation of the secreted cytokine profile, red clover extract is a putative candidate for preventing atherosclerosis and, thus, cardiovascular disease.
炎症和高脂血症或血脂异常会增加动脉粥样硬化和心血管疾病的风险。心血管疾病是全球主要的早逝原因之一。过氧化物酶体增殖物激活受体（PPAR）α的激活是治疗高脂血症和血脂异常的药物靶点，可改善血脂谱。在这项研究中，我们确定了红车轴草（一种替代目前用于治疗更年期症状的经典激素疗法的方法）的潜在抗炎和 PPARα刺激活性。
用脂多糖诱导的巨噬细胞作为抗炎活性模型，用嵌合 GAL4-PPARα系统作为潜在的降血脂活性模型。
红车轴草提取物和异黄酮染料木素和大豆苷元是中度的 PPARα激活剂。大豆苷元仅轻微激活 PPARα，但它的代谢物 6-羟基大豆苷元发挥了更高的 PPARα活性。同样，代谢物 3'-羟基染料木素的激活效率高于其前体染料木素。在脂多糖刺激的巨噬细胞中，红车轴草提取物及其化合物减少了促炎细胞因子白细胞介素-6 和肿瘤坏死因子-α的分泌，增加了抗炎白细胞介素-10 的分泌，和/或降低了核因子-κB、诱导型一氧化氮合酶和/或环氧化酶 2 的表达。生物素 A 和染料木素最有效地减少了肿瘤坏死因子-α的产生。白细胞介素-6 水平最有效地被染料木素和雌马酚降低。
由于其对 PPARα的激活作用和对分泌细胞因子谱的调节作用，红车轴草提取物是预防动脉粥样硬化和心血管疾病的潜在候选药物。
