姜黄素和Salsalate抑制高脂饮食，乙氧基甲烷处理的小鼠的结肠炎症和致癌信号。,Journal of Agricultural and Food Chemistry

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姜黄素和Salsalate抑制高脂饮食，乙氧基甲烷处理的小鼠的结肠炎症和致癌信号。
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2017-08-11 00:00:00 , DOI: 10.1021/acs.jafc.7b02648
Xian Wu , Anna C. Pfalzer ₁ , Gar Yee Koh , Sanyuan Tang ₂ , Jimmy W. Crott ₁ , Michael J. Thomas , Mohsen Meydani , Joel B. Mason ₁

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高脂饮食（HFD）和过量肥胖会增加结肠中的促炎细胞因子，从而以促进结直肠癌（CRC）发生的方式改变基因表达。因此，减少这种生化炎症的化合物是潜在的化学预防剂。饮食中的多酚姜黄素（CUR）和非甾体抗炎药salsalate（SAL）都是抗炎药。我们调查了在有或没有SAL的情况下CUR对乙氧基甲烷（AOM）治疗的A / J小鼠中炎性细胞因子和促癌信号的抑制作用。选择亚致瘤的AOM剂量以产生没有肿瘤的生化和分子致癌性结肠环境。给小鼠喂HFD（卡路里的60％）或低脂饮食（LFD）（卡路里的10％）。一个HFD治疗组的饮食中添加了0.2％的CUR。1人获得0.2％CUR + 0.15％SAL；其中一位收到0.4％CUR + 0.3％SAL。HFD小鼠的脂肪量比LFD小鼠大30％（p＜0.05）。通过高剂量联合方案，HFD小鼠的结肠中白介素-1β（IL-1β）和白介素-6（IL-6）的浓度降低了50–69％（p <0.015）。仅联合方案显着抑制蛋白激酶B（Akt）和核因子-κB（NF-κB）p65的磷酸化（p <0.044）。与单独使用CUR相比，CUR和SAL的组合降低了促炎细胞因子的浓度，并更有效地减少了Akt和NF-κB的激活，为研究这种组合是否减轻肥胖个体中CRC的风险提供了科学依据。

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Curcumin and Salsalate Suppresses Colonic Inflammation and Procarcinogenic Signaling in High-Fat-Fed, Azoxymethane-Treated Mice

High-fat diets (HFDs) and excess adiposity increase proinflammatory cytokines in the colon, altering gene expression in a manner that promotes the development of colorectal cancer (CRC). Thus, compounds that reduce this biochemical inflammation are potential chemopreventive agents. Curcumin (CUR), a dietary polyphenol, and salsalate (SAL), a non-steroidal anti-inflammatory drug, are both anti-inflammatories. We investigated the inhibitory effects of CUR with or without SAL on inflammatory cytokines and procarcinogenic signaling in azoxymethane (AOM)-treated A/J mice. A sub-tumorigenic AOM dose was chosen to produce a biochemical and molecular procarcinogenic colonic environment without tumors. Mice were fed either a HFD (60% of kilocalories) or low-fat diet (LFD) (10% of kilocalories). One HFD treatment group received 0.2% CUR in the diet; one received 0.2% CUR + 0.15% SAL; and one received 0.4% CUR + 0.3% SAL. The HFD mice developed 30% greater fat mass than the LFD mice (p < 0.05). The colonic concentrations of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the HFD mice were decreased by 50–69% by the high-dose combination regimen (p < 0.015). Only the combination regimens significantly suppressed phosphorylation of protein kinase B (Akt) and nuclear factor-κB (NF-κB) p65 (p < 0.044). The combination of CUR and SAL reduces the concentration of proinflammatory cytokines and diminishes activation of Akt and NF-κB more effectively than CUR alone, providing a scientific basis for examining whether this combination mitigates the risk of CRC in obese individuals.

更新日期：2017-08-11

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