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P023 Dipotassium glycyrrhizate normalises the mucosal healing gene expression altered by inflammation in a murine model of colitis

R. Vitali1, F. Palone1, S. Cucchiara*2, L. Stronati1

1ENEA, Department of Radiobiology and Humal Health, Rome, Italy, 2Sapienza, Rome, Pediatric Gastroenterology and Liver Unit, Rome, Italy

Background

Dipotassium glycyrrhizate (DPG) is a compound derived from glycyrrhizin, a glycoconjugated triterpene produced by the licorice plant, Glycyrrhiza glabra, whose anti-inflammatory properties are well-known. DPG reduce inflammation though various mechanisms, including the inhibition of the alarmin high mobility group box (HMGB)1 and the enzyme 11beta-hydroxysteroid dehydrogenase 2 (11betaHSD2). We previously demonstrated that DPG significantly reduces the DSS-induced colitis in mice, that showed a surprising recovery of body weight and large intestine length as well as an increase in histological score, the latter indicating the occurrence of a mucosal healing (MH).

The aim of the present study was to deeply investigate the effect of DPG on the expression of genes involved in the mucosal healing (MH) pathway during inflammation

Methods

C57BL/6 mice were divided into 3 experimental groups (5 mice for each group): DSS (3%)-treated mice, DSS (3%)+DPG (8mg/Kg)-treated mice and control mice. After 7 days, mice were sacrificed and the colon removed. Tissue samples were analysed by a PCR array (QIAGEN) able to evaluate 84 key genes central to the wound healing response. To identify the most altered genes, a threshold of 3.5 times was chosen. Selected genes were divided into functional groups. The expression level of the most altered genes inside each group was validated by RT-PCR

Results

DSS treatment significantly up-regulated 19 MH genes, as showed by comparing DSS-treated vs control mice. These genes were significantly down-regulated to control values by DPG treatment, as showed by comparing DSS+DPG mice vs DSS mice.

Altered genes were classified into 6 different functional groups: cytokines (IL-10, IL-1beta, IL-6), chemokines (CCL12, CCL7, CXCL1, CXCL3, CXCL5), extracellular matrix (ECM) components/collagen proteins (Col3a1, Vtn), growth factors (Csf3, Fgf2, Fgf7), remodelling enzymes (Mmp9, Timp1, Plat, Plaur, Serpine1), others (Ptgs2). Expression analysis of most altered genes within each functional group was validated by RT-PCR (p<0.001:IL-1beta, IL-6; p<0.01: CXCL3, CXCL5, Col3A1, Vtn, Fgf7; p<0.05: Mmp9, Serpine1).

Conclusion

We show for the first time that the use of DPG in mice with a DSS-induced colitis strongly improves the MH by modulating the expression levels of genes involved in wound healing response. Due to the total lack of side effects, we believe that DPG could represent a very innovative and useful tool for the management of human intestinal inflammation