Phloretin, a dihydrogen chalcone flavonoid, is mainly isolated from apples and strawberries. Phloretin has been proven to have many biological activities such as anti-inflammatory and anti-oxidative. Herein, we investigated the protective efficacy and potential mechanism of phloretin in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results showed that phloretin resulted in a reduced DSS-induced disease activity index (DAI), colon length shortening and colonic pathological damage. The levels of pro-inflammatory cytokines in the colon were also decreased by the administration of phloretin. Exploration of the potential mechanism demonstrated that phloretin suppressed the inflammatory response by regulating the nuclear factor-κB (NF-κB), toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Phloretin also inhibited the DSS-induced (NOD)-like receptor family and pyrin domain containing 3 (NLRP3) inflammasome activations. Further studies found that phloretin reduced key markers of oxidative stress as well as regulated the expression of zonula occludens-1 (ZO-1) and occludin. Interestingly, the concentration of serum lipopolysaccharide (LPS) was significantly decreased. Escherichia coli (E. coli) and Lactobacillus levels were also re-balanced after phloretin treatment. These results indicate that phloretin might be a new dietary strategy for the treatment of UC.

Evodiamine (EVO), an extraction from the traditional Chinese medicine Evodia rutaecarpa, has been reported to possess anti-inflammatory, anti-tumor and other pharmacological activities. However, the effectiveness of EVO to relieve dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) has not been evaluated. In this study, the protective effects and mechanisms of EVO on DSS-induced UC mice were investigated. The results indicated that treatment with EVO ameliorated DSS-induced UC mice body weight loss, disease activity index (DAI), colon length shortening, colonic pathological damage, and myeloperoxidase (MPO) activity. The production of TNF-α, IL-1β and IL-6 was also significantly inhibited by EVO. Further mechanistic results showed that EVO restrained the inflammation by regulating NF-κB signal and NLRP3 inflammasome. Furthermore, results also showed that EVO contributed to the tight junction (TJ) architecture integrity by modulating the expression of zonula occludens-1 (ZO-1) and occludin during colitis. Surprisingly, treatment with EVO reduced the concentration of plasmatic lipopolysaccharide (LPS) and re-balanced the levels of Escherichia coli and Lactobacillus. These findings suggested that EVO may have a potential protective effect on DSS-induced colitis and may be useful for the prevention and treatment of UC.