Beneficial health properties of black rice in dietary consumption and its major ingredient cyanidin 3- <i>O</i> -glucoside: a potential treatment for ulcerative colitis

Black rice, as a dietary supplement, has received increasing attention because of its beneficial health properties. Although black rice and its major ingredients have been considered a potential therapy for ulcerative colitis (UC), its effect and underlying mechanism of action remain obscure. In this study, black rice was demonstrated to improve dextran sulfate sodium salt (DSS)-induced UC and restore intestinal barrier dysfunction. Cyanidin 3-<i>O</i>-glucoside (C3G) is the most abundant ingredient in black rice. Similarly, <i>in vivo</i> and <i>in vitro</i> studies have demonstrated that C3G alleviates colitis and intestinal barrier dysfunction. Proteomic analysis showed that C3G significantly reduced abnormally elevated swiprosin-1 levels in mice with colitis. Furthermore, the effect of C3G on mitigating colitis was inhibited after swiprosin-1 was overexpressed in intestinal tissue <i>in vivo</i> and Caco-2 cells <i>in vitro</i>. Acyl-CoA synthetase long-chain family member 1 (ACSL1) was identified as a potential protein that interacts with swiprosin-1 by co-immunoprecipitation and liquid chromatography-tandem mass spectrometry. By integrating metabolomics experiments and bioinformatics analysis of single-cell sequencing, ACSL1 was found to selectively bind to swiprosin-1 and regulate downstream linoleic acid metabolism in colitis. Moreover, C3G was observed to prevent the localization of ACSL1 within mitochondria via swiprosin-1, thereby inhibiting the oxidation of linoleic acid. This study demonstrated that C3G targeted swiprosin-1 to ameliorate UC via ASCL1-mediated linoleic acid metabolism, thereby providing a novel potential insight into the mechanism of C3G protection against colitis and establishing the groundwork for its clinical application.