P095. Dipotassium glycyrrhizate ameliorates DSS-induced colitis in mice by HMGB1 inhibition
R. Vitali1, F. Palone1, L. Stronati1, A. Negroni1, E. Prete1, A. Di Lillo2, G. D'Arcangelo2, M. Aloi2, S. Cucchiara2, 1ENEA, Department of Radiobiology and Human Health, Rome, Italy, 2Sapienza University of Rome, Department of Pediatrics, Pediatric Gastroenterology & Liver Unit, Rome, Italy
Inflammatory bowel diseases (IBD) are chronic immune-mediated disorders of the gastrointestinal tract. Since IBD are currently not curable, it is crucial to identify innovative therapies.
High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can be released into extracellular milieu in response to stress or damage and subsequently activate the immune system and promote inflammation. HMGB1 has been implicated in several inflammatory and auto-immune disorders.
We previously showed that HMGB1 is secreted by inflamed intestinal tissues and is abundantly present in the feces of IBD patients, therefore it was proposed as a novel marker of intestinal mucosal inflammation.
Glycyrrhizin, a glycoconjugated triterpene produced by the root of licorice plant Glycyrrhiza glabra, exhibits anti-inflammatory properties and has been shown to importantly inhibit the cytokine activity of HMGB1. Thus, the aim of the present study is to assess the efficacy of a glycyrrhizin-derived compound, the dipotassium glycyrrhizate (DPG), in the treatment of chemical-induced murine colitis.
DPG (3–8 mg/kg) was administered to C57BL/6 mice after induction of chemical colitis by DSS. Body weight, clinical score, histological score, colon length/weight were evaluated in treated mice and compared to controls. Expression levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) and HMGB1 receptors (RAGE, TLR4) were also measured by RT-PCR. Fecal HMGB1 was analyzed by Western blot.
Mice exposed to DPG had a dramatic recovery of body weight (60%), total clinical score, histological score and large intestine length. Moreover, mice treated with DPG showed a significantly decrease in the mRNA levels of pro-inflammatory cytokines and HMGB1 receptors (p < 0.001). Finally, HMGB1 was found to be abundantly present in the feces of mice with DSS-induced colitis, but this amount was strongly reduced following DPG treatment (p < 0.01).
DPG showed excellent therapeutic properties for the treatment of DSS-induced murine colitis. We believe that these findings may open new perspectives in the setting of alternative strategies for the treatment of human IBD.