Department of Food and Biotechnology, Korea University, Sejong 30019, Korea.
R&D Center, Seoul Dairy Cooperative, Ansan, Kyunggi 425-839, Korea; Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Korea.
J Dairy Sci. 2020 Apr;103(4):2947-2955. doi: 10.3168/jds.2019-17411. Epub 2020 Jan 31.
Colorectal cancer (CRC) is known to be a life-threatening disease and commonly leads to metastasis in the liver. Fermented milk acts as an effective carrier for probiotic strains, whose consumption improves host health. Our previous study indicated that fermented milk that included a synbiotic combination of Lactobacillus gasseri 505 (505) and Cudrania tricuspidata leaf extract (CT) resulted in significantly greater anti-oxidative effects than fermented milk without CT. Therefore, we hypothesized that fermented milk containing CT and 505 (FCT) could result in hepatoprotective effects against CRC-induced liver metastasis. Liver inflammation and CRC were induced in male C57BL/6J mice, using azoxymethane/dextran sodium sulfate, and 505, CT, and FCT were administered to the 3 sample-treated 505, CT, and FCT groups, respectively, for 10 wk. The results showed that FCT treatment significantly reduced serum aspartate aminotransferase and alanine aminotransferase concentrations and elevated albumin concentrations. Moreover, the results of histological analysis showed that hepatic steatosis was notably reduced in the FCT group. Among the 3 sample-treated groups, the expression of mRNA associated with enzymes showing anti-oxidative activities, such as superoxide dismutase, catalase, and glutathione reductase, was the highest in the FCT-treated mice. In addition, FCT administration resulted in the greatest anti-inflammatory activity, as inflammatory marker levels (i.e., tumor necrosis factor-α, cyclooxygenase-2, myeloperoxidase, and nuclear factor kappa-light-chain enhancer of activated B cells) were significantly downregulated at the mRNA level and the expression of proteins associated with the nuclear factor kappa-light-chain enhancer of activated B cells and mitogen-activated protein kinase signaling pathways was suppressed by FCT. Therefore, this study demonstrated that fermented milk containing novel synbiotics has the potential to prevent hepatic toxicity induced because of CRC owing to its enhanced anti-oxidative and anti-inflammatory activities.
结直肠癌（CRC）是一种危及生命的疾病，通常会导致肝脏转移。发酵乳是益生菌菌株的有效载体，其消费可以改善宿主健康。我们之前的研究表明，含有共生组合的发酵乳Lactobacillus gasseri 505（505）和Cudrania tricuspidata 叶提取物（CT）的发酵乳比不含 CT 的发酵乳具有更显著的抗氧化作用。因此，我们假设含有 CT 和 505（FCT）的发酵乳可能对 CRC 诱导的肝转移具有肝保护作用。使用氧化偶氮甲烷/葡聚糖硫酸钠在雄性 C57BL/6J 小鼠中诱导肝炎症和 CRC，分别向 3 个样本处理组（505 组、CT 组和 FCT 组）中的 505、CT 和 FCT 组给予 505、CT 和 FCT 进行 10 周治疗。结果表明，FCT 治疗可显著降低血清天冬氨酸转氨酶和丙氨酸转氨酶浓度并升高白蛋白浓度。此外，组织学分析结果表明，FCT 组肝脂肪变性明显减少。在 3 个样本处理组中，FCT 处理组中与具有抗氧化活性的酶（如超氧化物歧化酶、过氧化氢酶和谷胱甘肽还原酶）相关的 mRNA 的表达最高。此外，FCT 给药导致最大的抗炎活性，因为炎性标志物水平（即肿瘤坏死因子-α、环氧化酶-2、髓过氧化物酶和核因子 kappa-轻链增强子的 B 细胞）在 mRNA 水平显著下调，与核因子 kappa-轻链增强子的 B 细胞和丝裂原活化蛋白激酶信号通路相关的蛋白质的表达被 FCT 抑制。因此，这项研究表明，含有新型共生体的发酵乳具有通过增强抗氧化和抗炎活性来预防 CRC 引起的肝毒性的潜力。
