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Dietary polyacetylene falcarinol upregulated intestinal heme oxygenase-1 and modified plasma cytokine profile in late phase lipopolysaccharide (LPS)-induced acute inflammation in CB57BL/6 mice
Nutrition Research ( IF 3.4 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.nutres.2020.06.014
Amanda Stefanson 1 , Marica Bakovic 1
Affiliation  

Unlike polyphenols, which are widely available in the diet, polyacetylenes are available only from the Apiaceae family vegetables, including carrot, parsnip, fennel, celery, and many herbs (parsley, lovage, etc). The aim of this study was to investigate the hypothesis that polyacetylene falcarinol (FA) reduces intestinal inflammation and examine its similarity of effect to isothiocyanate R-sulforaphane during the late phase of acute inflammation. To this end, 3-month-old male CB57BL/6 mice were fed twice daily for 1 week with 5 mg/kg of FA, sulforaphane, or vehicle before receiving an intraperitoneal injection of 5 mg/kg endotoxin (lipopolysaccharide [LPS]) to induce modest acute inflammation. The expression of intestinal and hepatic heme oxygenase-1 at the mRNA and protein levels, circulating cytokines, as well as intestinal and mesenteric n-6 and n-3 fatty acid lipid mediators was compared 24 hours after LPS administration to examine its effects on the late phase of inflammation. Intestinal nuclear factor (erythroid-derived 2)-like 2 target enzyme heme oxygenase-1 was upregulated 8.42-fold at the mRNA level and 10.7-fold at the protein level by FA-supplemented diet. However, the FA-supplemented diet produced a unique type-2 plasma cytokine skew after LPS treatment. Plasma cytokines interleukin (IL)-4, IL-13, IL-9, and IL-10 were upregulated, reflecting the cytokine profile of reduced type 1 inflammation. A detailed lipidomic analysis of n-6 and n-3 fatty acid pro- and anti-inflammatory pathways in the mesentery and intestinal mucosa showed that FA diet was more similar to the control groups than to other LPS treated groups. In this study, we demonstrated that FA-supplemented diet produced a unique immunomodulatory effect not observed with sulforaphane in late phases of inflammation. These results support the hypothesis that FA may have role as a dietary immunosuppressant in patients with inflammatory gastrointestinal as well as other inflammatory disorders that may be alleviated by increasing consumption of carrot or other FA-containing food sources.

中文翻译:

膳食聚乙炔镰刀菌素在 CB57BL/6 小鼠晚期脂多糖 (LPS) 诱导的急性炎症中上调肠血红素加氧酶-1 和改变的血浆细胞因子谱

与广泛存在于饮食中的多酚不同,聚乙炔只能从伞形科蔬菜中获得,包括胡萝卜、欧洲防风草、茴香、芹菜和许多草药(欧芹、独活草等)。本研究的目的是调查聚乙炔镰刀菌素 (FA) 减少肠道炎症的假设,并检查其在急性炎症后期与异硫氰酸酯 R-萝卜硫素作用的相似性。为此,在腹腔注射 5 mg/kg 内毒素(脂多糖 [LPS])之前,3 个月大的雄性 CB57BL/6 小鼠每天喂食两次 5 mg/kg FA、萝卜硫素或载体,持续 1 周诱发适度的急性炎症。肠道和肝脏血红素加氧酶-1 在 mRNA 和蛋白质水平的表达,循环细胞因子,以及肠和肠系膜 n-6 和 n-3 脂肪酸脂质介质在 LPS 给药后 24 小时进行比较,以检查其对炎症晚期的影响。通过补充 FA 的饮食,肠核因子(类红细胞衍生的 2)样 2 靶酶血红素加氧酶-1 在 mRNA 水平上调 8.42 倍,在蛋白质水平上调 10.7 倍。然而,补充 FA 的饮食在 LPS 治疗后产生了独特的 2 型血浆细胞因子偏斜。血浆细胞因子白介素 (IL)-4、IL-13、IL-9 和 IL-10 上调,反映了 1 型炎症减少的细胞因子谱。对肠系膜和肠粘膜中 n-6 和 n-3 脂肪酸促炎和抗炎途径的详细脂质组学分析表明,与其他 LPS 治疗组相比,FA 饮食与对照组更相似。在这项研究中,我们证明了添加 FA 的饮食产生了独特的免疫调节作用,而萝卜硫素在炎症晚期没有观察到。这些结果支持这样的假设,即 FA 可能在患有炎症性胃肠道和其他炎症性疾病的患者中起到膳食免疫抑制剂的作用,这些疾病可能通过增加胡萝卜或其他含 FA 的食物来源的摄入量来缓解。
更新日期:2020-08-01
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