Protective Effect of Ethyl Rosmarinate against Ulcerative Colitis in Mice Based on Untargeted Metabolomics

Int J Mol Sci. 2022 Jan 23;23(3):1256. doi: 10.3390/ijms23031256.

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.

Keywords: anti-inflammatory activity; ethyl rosmarinate; metabolomics; ulcerative colitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antioxidants / pharmacology
  • Biomarkers / blood
  • Cinnamates / pharmacology*
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism
  • Colon / pathology
  • Depsides / pharmacology*
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Inflammation / drug therapy
  • Male
  • Metabolomics / methods
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • RAW 264.7 Cells
  • Rats
  • Rosmarinic Acid
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Biomarkers
  • Cinnamates
  • Depsides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate