P3.31: Curcumin shifts the differentiation potential of intestinal stem cells toward the enterocyte lineage

Abstract

Introduction: Intestinal stem cell (ISC) is the fundamental unit for the regeneration of intestinal epithelium. Curcumin is a natural polyphenol extracted from the plant Curcuma longa. Curcumin has been found to have anti-inflammatory, anti-oxidation, as well as anti-cancer effects. In recent years, curcumin also was reported to regulate the activity of embryonic and mesenchymal stem cells. In this research we aimed to investigate the effects of curcumin on ISCs. Methods: Purified curcumin was purchased from Sigma-Aldrich. Mice ISCs were isolated from B6 mice and subjected to organoid culture under the treatment of curcumin at different concentrations for 10 days. At the end of treatment, the images of organoids under each treatment group were photographed by microscopic cameras, and the organoid morphology, number, and area were further analyzed by ImageJ software. The ISC markers of proliferation and differentiation were analyzes by real-time PCR, and immuno-fluorescence staining. Results: The average number of the organoids was 33, 47, 43, and 20 per well after the treatment of 0, 1, 5, and 25 μM of curcumin, respectively. The average size of organoid was significantly larger in the curcumin-treated groups (Figure 1). The ISC proliferation markers Lgr5 showed modest decrease after curcumin treatment: 0. 66- (1 μM), 0. 74- (5 μM), and 0. 56- (25 μM) fold compared with the control. Of the four differentiation markers, curcumin treatment resulted in significant increase of villin with 1. 87- (1 μM), 2. 19- (5 μM), and 12. 21- (25 μM) fold increase. Confocal imaging of anti-villin-stained organoids also demonstrated more abundant villin expression in the organoids under curcumin treatment (Figure 2). Conclusion: ISCs treated by curcumin showed significant upregulation of villin, which represents the differentiation potential toward “enterocyte”, which makes up the absorptive function of intestinal epithelium. The molecular mechanism of this effect and its clinical application is under investigation in the in vivo mice model.