Department of Food Science and Nutrition, Pukyong National University, Pusan, 608-737, Republic of Korea,
Arch Pharm Res. 2014 Oct;37(10):1354-63. doi: 10.1007/s12272-014-0351-3. Epub 2014 Mar 24.
To investigate the effect of C-glycosylation at different positions of luteolin, the structure-activity relationships of luteolin and a pair of isomeric C-glycosylated derivatives orientin and isoorientin, were evaluated. We investigated the effects of C-glycosylation on the antioxidant, anti-Alzheimer's disease (AD), anti-diabetic and anti-inflammatory effects of luteolin and its two C-glycosides via in vitro assays of peroxynitrite (ONOO(-)), total reactive oxygen species (ROS), nitric oxide (NO), 1,1-diphenyl-2-picrylhydraxyl (DPPH), aldose reductase, protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor cleaving enzyme 1 (BACE1), and cellular assays of NO production and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Of the three compounds, isoorientin showed the highest scavenging activity against DPPH, NO, and ONOO(-), while luteolin was the most potent inhibitor of ROS generation. In addition, luteolin showed the most potent anti-AD activity as determined by its inhibition of AChE, BChE, and BACE1. With respect to anti-diabetic effects, luteolin exerted the strongest inhibitory activity against PTP1B and rat lens aldose reductase. Luteolin also inhibited NO production and iNOS protein expression in LPS-stimulated macrophages, while orientin and isoorientin were inactive at the same concentrations. The effects of C-glycosylation at different positions of luteolin may be closely linked to the intensity and modulation of antioxidant, anti-AD, anti-diabetic, and anti-inflammatory effects of luteolin and its C-glycosylated derivatives.
为了研究木樨草素不同位置 C-糖苷化的效果，评估了木樨草素及其一对同分异构体 C-糖苷化衍生物芹菜素和异芹菜素的结构-活性关系。我们通过过氧亚硝酸盐 (ONOO(-))、总活性氧 (ROS)、一氧化氮 (NO)、1,1-二苯基-2-苦基肼基 (DPPH)、醛糖还原酶、蛋白酪氨酸磷酸酶 1B (PTP1B)、乙酰胆碱酯酶 (AChE)、丁酰胆碱酯酶 (BChE) 和β-位淀粉样前体蛋白裂解酶 1 (BACE1) 的体外测定以及脂多糖 (LPS) 刺激的 RAW 264.7 细胞中 NO 产生和诱导型一氧化氮合酶 (iNOS)/环加氧酶-2 表达的细胞测定，研究了 C-糖苷化对木樨草素及其两种 C-糖苷的抗氧化、抗阿尔茨海默病 (AD)、抗糖尿病和抗炎作用的影响。在这三种化合物中，异芹菜素对 DPPH、NO 和 ONOO(-) 的清除活性最高，而木樨草素对 ROS 生成的抑制作用最强。此外，木樨草素对 AChE、BChE 和 BACE1 的抑制作用最强，表现出最强的抗 AD 活性。关于抗糖尿病作用，木樨草素对 PTP1B 和大鼠晶状体醛糖还原酶表现出最强的抑制活性。木樨草素还抑制 LPS 刺激的巨噬细胞中 NO 的产生和 iNOS 蛋白表达，而芹菜素和异芹菜素在相同浓度下无活性。木樨草素不同位置 C-糖苷化的效果可能与木樨草素及其 C-糖苷化衍生物的抗氧化、抗 AD、抗糖尿病和抗炎作用的强度和调节密切相关。
