Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI)-Campus Itajaí, Santa Catarina, Brazil. Rua Uruguai, 458, Centro. CEP: 88302-901.
Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI)-Campus Itajaí, Santa Catarina, Brazil. Rua Uruguai, 458, Centro. CEP: 88302-901.
Nutr Res. 2019 Jun;66:95-106. doi: 10.1016/j.nutres.2019.03.005. Epub 2019 Mar 8.
Given the role of oxidative stress in ulcerative colitis (UC) etiology, and the amount of lutein (a carotenoid with antioxidant properties) in the dry hydroalcoholic extract of Tagetes erecta flowers (DHETE), this study investigated the intestinal anti-inflammatory properties of DHETE in an animal model of UC. The amount of lutein in the extract was determined by H-nuclear magnetic resonance spectroscopy, and total phenols, radical scavenger capability, cytotoxicity, and effects on reactive oxygen species and nitric oxide production were evaluated in vitro. Experimental UC was established by adding 5% dextran sulfate sodium (DSS) to drinking water, with the effects of DHETE (30-300 mg/kg, once a day for 7 days) on the morphological (colon length and weight), clinical (disease activity index and body weight loss), microscopic (histological score and mucin levels), and biochemical parameters analyzed. The lutein concentration found in DHETE was 8.2%, and DHETE scavenged 2,2-diphenyl-1-picrylhydrazyl radicals at 1000 μg/mL The exposure of intestinal epithelial cells to DHETE did not change its viability but reduced reactive oxygen species and nitric oxide production after lipopolysaccharide stimulation. In vivo, DHETE (300 mg/kg) attenuated weight loss, disease activity index, colon shortening, and histopathological changes promoted by DSS intake. Moreover, DHETE increased mucin colonic staining. The treatment with DHETE decreased myeloperoxidase activity as well as tumor necrosis factor and interleukin-6 levels. The extract also increased reduced glutathione levels and catalase activity and normalized superoxide dismutase and glutathione-S-transferase activities. In conclusion, DHETE reduced colitis severity by attenuating inflammatory cytokine secretion and improved the endogenous antioxidant defense in DSS-induced UC in mice.
鉴于氧化应激在溃疡性结肠炎（UC）发病机制中的作用，以及叶黄素（一种具有抗氧化特性的类胡萝卜素）在 Tagetes erecta 花干水醇提取物（DHETE）中的含量，本研究在 UC 动物模型中研究了 DHETE 的肠道抗炎特性。通过 H-核磁共振波谱法测定提取物中的叶黄素含量，并在体外评估总酚类、自由基清除能力、细胞毒性以及对活性氧和一氧化氮产生的影响。通过在饮用水中添加 5%葡聚糖硫酸钠（DSS）建立实验性 UC，分析 DHETE（30-300mg/kg，每天一次，共 7 天）对形态学（结肠长度和重量）、临床（疾病活动指数和体重减轻）、微观（组织学评分和粘蛋白水平）和生化参数的影响。DHETE 中的叶黄素浓度为 8.2%，DHETE 在 1000μg/mL 时清除 2,2-二苯基-1-苦基肼自由基。DHETE 暴露于肠上皮细胞不会改变其活力，但可降低脂多糖刺激后的活性氧和一氧化氮产生。在体内，DHETE（300mg/kg）减轻了 DSS 摄入引起的体重减轻、疾病活动指数、结肠缩短和组织病理学变化。此外，DHETE 增加了粘蛋白的结肠染色。DHETE 治疗降低了髓过氧化物酶活性以及肿瘤坏死因子和白细胞介素-6 水平。该提取物还增加了还原型谷胱甘肽水平和过氧化氢酶活性，并使超氧化物歧化酶和谷胱甘肽-S-转移酶的活性正常化。综上所述，DHETE 通过减轻炎症细胞因子的分泌减轻结肠炎的严重程度，并改善 DSS 诱导的 UC 小鼠内源性抗氧化防御。
