Abstract

Aiming at assessing the therapeutic effect of ethyl rosmarinate (ER) on ulcerative colitis (UC), the following activities were performed in vitro and in vivo in the present study. Firstly, a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to determine the level of inflammatory factors. Then, a UC mice model induced by dextran sodium sulfate (DSS) was established to further investigate the effects of ER on symptoms, inflammatory factors and colon histopathology. Finally, serum and colon metabolomics studies were performed to identify the biomarkers and metabolisms closely related to the protective effect of ER on UC. The results showed that after ER intervention, the levels of inflammatory factors (NO, TNF-α, IL-1β and IL-6) and key enzyme (MPO) in cell supernatant, serum or colon were significantly decreased, and the disease activity index and colon tissue damage in mice were also effectively improved or restored. In addition, 28 biomarkers and 6 metabolisms were found to be re-regulated by ER in the UC model mice. Therefore, it could be concluded that ER could effectively ameliorate the progression of UC and could be used as a new natural agent for the treatment of UC.

Highlights

  • Ulcerative colitis (UC), a globally prevalent form of inflammatory bowel disease, often causes bloody diarrhea, weight loss, rectal bleeding, and even significantly increases the risk of colorectal cancer [1,2,3]

  • AsAshown in Figure 1B, the levels of NBO, IL-6, TNF-α and IL-1β of the model group were all significantly increased compared with the control group (p < 0.001), which showed the inflammation was successfully induced

  • The high activity of MPO in UC model mice was notably reduced in the ethyl rosmarinate (ER)-treated groups, which suggested that ER could effectively inhibit neutrophil infiltration

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Summary

Introduction

Ulcerative colitis (UC), a globally prevalent form of inflammatory bowel disease, often causes bloody diarrhea, weight loss, rectal bleeding, and even significantly increases the risk of colorectal cancer [1,2,3]. Drug intervention is the main method for the treatment of UC. The drugs commonly used in clinics are 5-aminosalicylic acid, sulfasalazine, dexamethasone and infliximab, etc. There are still some disadvantages such as the unsatisfactory curative effect, poor oral absorption, low tolerability and high cost. It is necessary to develop novel anti-UC drugs. With unique efficacy, multiple targets, toleration, biocompatibility, low toxicity and a realistic price advantage is receiving more and more attention [7]

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