The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer's disease, anti-diabetic, and anti-inflammatory activities
The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer's disease, anti-diabetic, and anti-inflammatory activities
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DOI：
10.1007/s12272-014-0351-3
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发表时间：
2014-10-01
影响因子：
6.7
通讯作者：
Jung, Hyun Ah
中科院分区：
文献类型：
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作者：
Choi, Jae Sue;Islam, Md Nurul;Jung, Hyun Ah
为了研究木樨草素不同位置的C-糖基化作用，评价了木樨草素和一对异构的C-糖基化衍生物orientin和isoorientin的构效关系。通过体外过氧化亚硝酸根（ONOO-）、总活性氧（ROS）、一氧化氮（NO）、1，1-二苯基-2-苦基肼（DPPH）、醛糖还原酶、蛋白酪氨酸磷酸酶1B（PTP 1B）、乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）和β位点淀粉样蛋白前体切割酶1（BACE 1），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）/环氧合酶-2表达的细胞测定。在这三种化合物中，异Orientin对DPPH，NO和ONOO-的清除活性最高，而木犀草素是最有效的ROS生成抑制剂。此外，毛地黄黄酮显示出最有效的抗AD活性，通过其对AChE，BChE和BACE 1的抑制来确定。在抗糖尿病作用方面，毛地黄黄酮对PTP 1B和大鼠透镜醛糖还原酶的抑制作用最强。木犀草素还抑制LPS刺激的巨噬细胞中NO的产生和iNOS蛋白的表达，而Orientin和isoorientin在相同浓度下无活性。木樨草素不同位置的C-糖基化作用可能与木樨草素及其C-糖基化衍生物的抗氧化、抗AD、抗糖尿病和抗炎作用的强度和调节密切相关。
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 beta-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.