Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China.
Mar Drugs. 2022 Jan 24;20(2):96. doi: 10.3390/md20020096.
Chitosan oligosaccharides (COS) have been shown to have potential protective effects against colitis, but the mechanism underlying this effect has not been fully elucidated. In this study, COS were found to significantly attenuate dextran sodium sulfate-induced colitis in mice by decreasing disease activity index scores, downregulating pro-inflammatory cytokines, and upregulating Mucin-2 levels. COS also significantly inhibited the levels of nitric oxide (NO) and IL-6 in lipopolysaccharide-stimulated RAW 264.7 cells. Importantly, COS inhibited the activation of the NF-κB signaling pathway via activating PPARγ and SIRT1, thus reducing the production of NO and IL-6. The antagonist of PPARγ could abolish the anti-inflammatory effects of COS in LPS-treated cells. COS also activated SIRT1 to reduce the acetylation of p65 protein at lysine 310, which was reversed by silencing SIRT1 by siRNA. Moreover, COS treatment increased the diversity of intestinal microbiota and partly restored the / ratio. COS administration could optimize intestinal microbiota composition by increasing the abundance of , and while decreasing the abundance of . Furthermore, COS could also increase the levels of propionate and butyrate. Overall, COS can improve colitis by regulating intestinal microbiota and the PPARγ/SIRT1-mediated NF-κB pathway.
壳寡糖（COS）已被证明对结肠炎具有潜在的保护作用，但这种作用的机制尚未完全阐明。在这项研究中，COS 通过降低疾病活动指数评分、下调促炎细胞因子和上调粘蛋白-2水平，显著减轻了葡聚糖硫酸钠诱导的小鼠结肠炎。COS 还显著抑制了脂多糖刺激的 RAW 264.7 细胞中一氧化氮（NO）和白细胞介素-6（IL-6）的水平。重要的是，COS 通过激活 PPARγ 和 SIRT1 抑制 NF-κB 信号通路的激活，从而减少 NO 和 IL-6 的产生。PPARγ 的拮抗剂可以消除 COS 在 LPS 处理的细胞中的抗炎作用。COS 还通过沉默 SIRT1 的 siRNA 激活 SIRT1 来减少 p65 蛋白赖氨酸 310 处的乙酰化。此外，COS 处理增加了肠道微生物群的多样性，并部分恢复了 / 比值。COS 通过增加、和的丰度，同时减少的丰度来优化肠道微生物群组成。此外，COS 还可以增加丙酸盐和丁酸盐的水平。总的来说，COS 可以通过调节肠道微生物群和 PPARγ/SIRT1 介导的 NF-κB 通路来改善结肠炎。
