Preventive Effects of an UPLC-DAD-MS/MS Fingerprinted Hydroalcoholic Extract of Citrus aurantium in a Mouse Model of Ulcerative Colitis

Planta Med. 2018 Oct;84(15):1101-1109. doi: 10.1055/a-0604-2797. Epub 2018 May 4.


Although traditionally used to improve indigestion, diarrhea, dysentery, and constipation, the therapeutic effects of Citrus aurantium on intestinal inflammation remain unclear. The aim of this study was to evaluate the beneficial effects and to identify the active components of a hydroalcoholic extract of C. aurantium (HECA) on ulcerative colitis. HECA was prepared with 70% ethanol solution in water and extracted at 37 °C for 12 h in triplicate, filtered through a sieve, and lyophilized. Phytochemical identification of HECA was performed by ultra-performance liquid chromatography-diode array detector-tandem mass spectrometry (UPLC-DAD-MS/MS). Animals were randomly assigned to one of four groups based on the treatment conditions. Ulcerative colitis was induced by administration of 2.5% dextran sodium sulfate (DSS) in drinking water for 5 d. Body weight, clinical signs, colon length, pro-inflammatory cytokine expression levels, and histopathological findings were evaluated. In UPLC-DAD-MS/MS analysis, the identified phytochemical components of HECA included four alkaloids, seven coumarins, 18 flavonoids, two lignans, two phenolics, and 10 terpenoids. HECA markedly protected against body weight loss and colon shortening. In pathological examination, HECA alleviated DSS-related mucosal inflammatory lesions in the colon. Moreover, HECA markedly reduced the expression levels of interleukin-6, interferon-γ, tumor necrosis factor-α, and monocyte chemotactic protein-1 in colonic inflammation. Taken together, HECA has potential to relieve mucosal inflammation in the colon, suggesting that the putative active ingredients are responsible for the anti-ulcerative effects.

MeSH terms

  • Animals
  • Citrus / chemistry*
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / pathology
  • Colitis, Ulcerative / prevention & control*
  • Colon / drug effects
  • Colon / pathology
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Dextran Sulfate / administration & dosage
  • Disease Models, Animal
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Random Allocation
  • Tandem Mass Spectrometry


  • Cytokines
  • Plant Extracts
  • Dextran Sulfate