Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Sciences, South China Agricultural University, Guangzhou, China.
Department of Food Science, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Food Funct. 2023 May 11;14(9):4414-4429. doi: 10.1039/d3fo00516j.
5-Demethylnobiletin (5DN) is an important ingredient of citrus extract that is rich in polymethoxyflavones (PMFs). In this study, we systemically investigated the preventive effects of 5DN on antibiotic-associated intestinal disturbances. Experimental mice were gavaged 0.2 mL per day of the antibiotic cocktail (12.5 g L cefuroxime and 10 g L levofloxacin) for 10 days, accompanied by dietary 0.05% 5DN for 10 and 20 days. The results showed that the combination of cefuroxime and levofloxacin caused swelling of the cecum and injury to the colon tissue. Meanwhile, the balance of intestinal oxidative stress and the barrier function of mice was also damaged by the antibiotics through upregulation of the relative mRNA levels of superoxide dismutase 3 (SOD3), quinine oxidoreductase 1 (NQO1) and glutathione peroxidase 1 (GPX1), and downregulation of the relative protein levels of tight junction proteins (TJs). Moreover, antibiotic exposure led to disorder of the gut microbiota, particularly increased harmful bacteria (Proteobacteria) and decreased beneficial bacteria (Bacteroideta). However, dietary 5DN could reduce antibiotic-associated intestinal damage, evidenced by the results that 5DN alleviated gut oxidative damage and attenuated intestinal barrier injury increasing the expression of TJs including occludin and zonula occluden1 (ZO1). Additionally, dietary 5DN modulated the composition of the gut microbiota in antibiotic-treated mice by increasing the relative levels of beneficial bacteria, such as and . Moreover, PMFs increased the contents of isobutyric acid and butyric acid, which were almost eliminated by antibiotic exposure. In conclusion, 5DN could alleviate antibiotic-related imbalance of intestinal oxidative stress, barrier function damage, intestinal flora disorders and the reduction of short-chain fatty acids (SCFAs), which lays a foundation for exploring safer and more effective ways to prevent or mitigate antibiotic-associated intestinal damage.
5-去甲川陈皮素（5DN）是柑橘提取物中的一种重要成分，富含多甲氧基黄酮（PMFs）。在本研究中，我们系统地研究了 5DN 对抗生素相关肠道紊乱的预防作用。实验小鼠每天灌胃 0.2mL 抗生素鸡尾酒（12.5g L 头孢呋辛和 10g L 左氧氟沙星），同时连续 10 天和 20 天给予饮食中 0.05%的 5DN。结果表明，头孢呋辛和左氧氟沙星联用会导致盲肠肿胀和结肠组织损伤。同时，抗生素通过上调超氧化物歧化酶 3（SOD3）、醌氧化还原酶 1（NQO1）和谷胱甘肽过氧化物酶 1（GPX1）的相对 mRNA 水平，下调紧密连接蛋白（TJs）的相对蛋白水平，破坏了小鼠的肠道氧化应激平衡和屏障功能。此外，抗生素暴露导致肠道微生物群紊乱，特别是有害细菌（变形菌门）增加，有益细菌（拟杆菌门）减少。然而，饮食中添加 5DN 可减轻抗生素相关的肠道损伤，这表现在 5DN 减轻了肠道氧化损伤，减弱了肠道屏障损伤，增加了 TJs 的表达，包括紧密连接蛋白 1（occludin）和紧密连接蛋白 1（ZO1）。此外，饮食中添加 5DN 通过增加有益细菌的相对水平来调节抗生素处理小鼠的肠道微生物群组成，例如 和 。此外，PMFs 增加了异丁酸和丁酸的含量，而这些物质几乎被抗生素暴露所消除。总之，5DN 可以缓解抗生素相关的肠道氧化应激、屏障功能损伤、肠道菌群失调和短链脂肪酸（SCFAs）减少的失衡，为探索更安全、更有效的预防或减轻抗生素相关肠道损伤的方法奠定了基础。
