Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Rd E, Guelph, Ontario, Canada N1G 2W1.
Nutr Res. 2020 Aug;80:89-105. doi: 10.1016/j.nutres.2020.06.014. Epub 2020 Jun 25.
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.
与广泛存在于饮食中的多酚不同，多炔类化合物仅存在于伞形科蔬菜中，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）。本研究旨在验证这样一个假设，即多炔类化合物法卡林醇（FA）可减轻肠道炎症，并研究其在急性炎症晚期的作用与异硫氰酸酯 R-硫代葡萄糖苷类似。为此，3 月龄雄性 CB57BL/6 小鼠每天两次接受 5mg/kg 的 FA、硫代葡萄糖苷或载体喂养 1 周，然后接受 5mg/kg 内毒素（脂多糖 [LPS]）腹腔注射，以诱导适度的急性炎症。在 LPS 给药后 24 小时，比较肠道和肝脏血红素加氧酶-1 的 mRNA 和蛋白表达、循环细胞因子以及肠道和肠系膜 n-6 和 n-3 脂肪酸脂质介质，以检查其对炎症晚期的影响。肠道核因子（红系衍生 2）样 2 靶酶血红素加氧酶-1 的 mRNA 水平上调 8.42 倍，蛋白水平上调 10.7 倍。然而，FA 补充饮食在 LPS 处理后产生了一种独特的 2 型血浆细胞因子偏倚。血浆细胞因子白细胞介素（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。对肠系膜和肠黏膜中 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，FA 饮食与对照组更相似，而与其他 LPS 处理组差异更大。在这项研究中，我们证明了 FA 补充饮食产生了一种独特的免疫调节作用，这在炎症晚期与硫代葡萄糖苷不同。这些结果支持了这样一个假设，即 FA 可能作为一种饮食免疫抑制剂，在患有炎症性胃肠道疾病以及其他炎症性疾病的患者中发挥作用，这些疾病可能通过增加胡萝卜或其他含有 FA 的食物来源的摄入而得到缓解。
