Pretreatment with licochalcone a enhances therapeutic activity of rat bone marrow mesenchymal stem cells in animal models of colitis

Objective(s): Colitis has a high prevalence rate, limited treatment options, and needs to be solved urgently. Application of Licochacone A (LA) or rBMMSCs alone in the treatment of colitis has a certain but limited effect. This study aims to develop an LA-based strategy to improve mesenchymal stem cells' (MSCs') therapeutic capacity in mice DSS-induced colitis by increasing the number of MSCs migrating to the inflammation site. Materials and Methods: In vivo, we injected MSCs pretreated with LA, MSCs alone, or PBS into the tail vein of colitis mice, and assessed the colon length, disease activity index (DAI) score, body weight, HAI score, and tracked the location of MSCs at day 10. In vitro, we knocked down the CXCR4 gene by siRNA and then treated it with LA, then tested the mRNA level of CXCR4 and the migration ability of group CXCR4, CXCR4+LA, LA, and control to verify the relationship between this effect and the SDF-1-CXCR4 signaling pathway. Results: The mice that received LA-pretreated MSCs had ameliorated body weight loss, preserved colon morphology, and decreased DAI and histological activity index (HAI) compared with the MSCs group. Besides, the number of MSCs migrating to the inflammation site significantly increased in group LA+MSCs, and expression of CXCR4 significantly increased too. Furthermore, we found that LA could partly revise the decrease of the migration of MSCs and the expression of CXCR4 mRNA caused by CXCR4-siRNA. Conclusion: LA may improve the migration ability of MSCs through increasing CXCR4 expression therapy enhancing their therapeutic activity.