Protective effects and potential mechanism of Cyclocarya paliurus (Batal.) Iljinskaja flavonoids on DSS-induced colitis in mice

This study identified the chemical composition of Cyclocarya paliurus (Batal.) Iljinskaja flavonoids (CPF) and evaluated the antioxidant activities of 40% ethanol-eluted (EE)-CPF and 70% EE-CPF. Then we investigated whether 40% EE-CPF with stronger antioxidant capacity and higher flavonoid content exerted alleviative effects on dextran sulfate sodium (DSS)-induced colitis in mice. Our resulted showed that 40% EE-CPF improved colitis symptoms and colon tissue damage, as evidenced by the increased body weight, enhanced colon length, reduced disease activity index (DAI) score and increased goblet cells. Moreover, CPF reduced oxidative stress by regulating superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels, and restored intestinal barrier through Toll-like receptor 4(TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, thereby exhibiting preventive effects on colitis in mice induced by DSS. Additionally, CPF regulated the composition of gut microbiota, leading to the increased beneficial microbiota, e.g., Lactobacillus and decreased harmful microbiota, e.g., Mucispirillum. Meanwhile, CPF increased the levels of short-chain fatty acids in cecal contents of mice. More interestingly, through microbiota functional analysis and correlation analysis, we proposed that CPF may alleviate colitis via microbial metabolism involved glycolysis Ⅲ and pyruvate fermentation pathways. Collectively, these results established a theoretical reference for developing CPF as anti-inflammatory agents in colitis.