Yang Haixia, Du Zheyuan, Wang Weicang, Song Mingyue, Sanidad Katherine, Sukamtoh Elvira, Zheng Jennifer, Tian Li, Xiao Hang, Liu Zhenhua, Zhang Guodong
Department of Food Science, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Department of Nutrition and Food Safety, College of Public Health, Xi'an Jiaotong University , Xi'an, Shaanxi, China 710061.
J Agric Food Chem. 2017 Jun 7;65(22):4509-4515. doi: 10.1021/acs.jafc.7b01792. Epub 2017 May 23.
Curcumin, a dietary compound from turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease. Most previous studies have focused on the structure-activity relationship of the thiol-reactive α,β-unsaturated carbonyl groups of curcumin, so little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogues with different substitution groups (R = H-, Br-, Cl-, F-, NO-, CH-, and OH-) to replace the methoxy group and evaluated their biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 μM) suppressed 74.91 ± 0.88, 77.75 ± 0.89, and 71.75 ± 0.90% of LPS-induced NO production, respectively (P < 0.05). Similarly, these compounds also decreased iNOS expression, COX-2 expression, and NF-κB signaling in RAW 264.7 macrophage cells (P < 0.05). However, other analogues, especially Cur-NO, were inactive (P > 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse model, the Cur-Br analogue also showed a beneficial effect the same as curcumin (P < 0.05), whereas the Cur-NO analogue had no effect in the animal model (P > 0.05). Together, the analogues have dramatically different effects on inflammation, supporting that the substitution group on the methoxy position plays an important role in the anti-inflammatory effects of curcumin. The methoxy group is a potential structural candidate for modification to design curcumin-based drugs for inflammatory diseases.
姜黄素是一种从姜黄中提取的膳食化合物，对炎症性疾病如炎症性肠病具有有益作用。此前大多数研究都集中在姜黄素的硫醇反应性α,β-不饱和羰基的构效关系上，因此对甲氧基在姜黄素生物活性中的作用了解甚少。在此，我们合成了一系列具有不同取代基（R = H-、Br-、Cl-、F-、NO-、CH-和OH-）的姜黄素类似物来取代甲氧基，并评估了它们在体外和体内的生物学效应。姜黄素、Cur-OH和Cur-Br（25 μM）分别抑制了脂多糖诱导的一氧化氮生成的74.91±0.88%、77.75±0.89%和71.75±0.90%（P < 0.05）。同样，这些化合物也降低了RAW 264.7巨噬细胞中的诱导型一氧化氮合酶表达、环氧化酶-2表达和核因子κB信号传导（P < 0.05）。然而，其他类似物，尤其是Cur-NO，没有活性（P > 0.05）。在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中，Cur-Br类似物也显示出与姜黄素相同的有益效果（P < 0.05），而Cur-NO类似物在动物模型中没有效果（P > 0.05）。总之，这些类似物对炎症具有显著不同的影响，支持甲氧基位置上的取代基在姜黄素的抗炎作用中起重要作用。甲氧基是设计用于炎症性疾病的基于姜黄素的药物的潜在结构修饰候选基团。
