新型羽扇豆醇衍生查耳酮的抗血脂异常和抗氧化作用。
Antidyslipidemic and antioxidant effects of novel Lupeol-derived chalcones.
作者信息
Srivastava Shishir, Sonkar Ravi, Mishra Sunil Kumar, Tiwari Avinash, Balaramnavar Vishal M, Mir Snober, Bhatia Gitika, Saxena Anil K, Lakshmi Vijai
机构信息
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow, 226 001, India.
出版信息
Lipids. 2013 Oct;48(10):1017-27. doi: 10.1007/s11745-013-3824-0. Epub 2013 Aug 14.
A series of Lupeol-based chalcones have been synthesized aiming to enhance the therapeutic efficacy of parent compound, the novel compounds were evaluated for their antidyslipidemic activity in triton-WR 1339 induced hyperlipidemic rats. Among the ten synthesized chalcones, the most active K4, K8, and K9 reversed the plasma levels of TC by (24, 25, 27 %), phospholipid by (25, 26, 25 %) and triacylglycerol by (27, 24, 24 %) respectively. In addition, the compounds showed significant in vitro antioxidant activity. The lipid lowering activity of these compounds were mediated through lipoprotein lipase activation (12-21 %) and enhanced post-heparin lipolytic activity (15-16 %). The compounds also displayed noteworthy inhibitory effect on 3-hydroxy-3-methyl-glutaryl reductase activity (in vitro). The in vitro effect of the most active compounds on MDI-induced adipogenesis using 3T3-L1 preadipocytes at 10 and 20 μM concentrations showed significant inhibition (20-32 %) of adipogenesis.
为了提高母体化合物的治疗效果，已合成了一系列基于羽扇豆醇的查耳酮，对这些新化合物在 Triton-WR 1339 诱导的高脂血症大鼠中的抗血脂异常活性进行了评估。在合成的十种查耳酮中，活性最高的 K4、K8 和 K9 分别使总胆固醇（TC）的血浆水平降低了（24%、25%、27%），磷脂降低了（25%、26%、25%），三酰甘油降低了（27%、24%、24%）。此外，这些化合物在体外显示出显著的抗氧化活性。这些化合物的降脂活性是通过脂蛋白脂肪酶激活（12%-21%）和增强肝素后脂解活性（15%-16%）介导的。这些化合物在体外对 3-羟基-3-甲基戊二酰辅酶 A 还原酶活性也表现出显著的抑制作用。使用 3T3-L1 前脂肪细胞，在 10 和 20 μM 浓度下，活性最高的化合物对 MDI 诱导的脂肪生成的体外作用显示出对脂肪生成的显著抑制（20%-32%）。
Zotero 插件