Protective Effect of Betulinic Acid against Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

To study the effect of betulinic acid (BA) on dextran sodium sulfate (DSS)-induced ulcerative colitis.

Eighty-four C57BL/6 mice were randomly divided into 7 groups, namely control, BA (0.5 mg/kg), DSS (4% by mass), low-, medium- and high-dose (0.25, 0.5 and 1 mg/kg) BA + DSS, and 5-aminosalicylic acid (5-ASA) (50 mg/kg) + DSS groups. BA or 5-ASA was gavaged continuously for 14 days, and 4% DSS solution was consumed every day from the 8th day to induce colitis in mice for 7 consecutive days. Afterwards, the length of the colon was measured, the pathological changes and ultrastructure were observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy, the level of reactive oxygen species (ROS) was measured by immunofluorescence staining, inflammatory factors were detected by real-time polymerase chain reaction (real-time PCR), and cell apoptosis was observed by TUNEL staining.

After DSS treatment, the length of the colon was significantly decreased (P < 0.05), the arrangement of intestinal crypts became disordered with irregular surfaces, and the number of goblet cells was reduced, which was accompanied by incomplete intestinal tight junctions and sparse microvilli. Meanwhile, DSS induced the accumulation of ROS and significantly up-regulated the mRNA levels of the inflammatory cytokines interleukin-1β (IL-1β), IL-6, and IL-10 (P < 0.01), down-regulated the mRNA expression of tumor necrosis factor-α (P < 0.01) in the colon, and promoted cell apoptosis (P < 0.01). However, pretreatment with either BA or 5-ASA could reverse these phenomena, and the effect of BA was better than that of 5-ASA.

BA has a preventive or protective effect against DSS-induced colitis by improving the integrity of intestinal structure, reducing ROS production, improving the inflammatory response and inhibiting apoptosis.