Delphinidin induces the upregulation of miR-23a-3p expression in skeletal muscle and miR-23a-3p release from intestinal cells.

Delphinidin, one of the major anthocyanidins, inhibits disuse muscle atrophy by increasing the expression of miR-23a-3p in mouse skeletal muscle. However, delphinidin is less stable and poorly absorbed in vivo, so its mechanism of function remains unclear. In this study, we aimed to elucidate the mechanism by which delphinidin increases miR-23a-3p expression in skeletal muscle. miRNAs can be packaged into extracellular vesicles (EVs) and secreted from cells. We investigated whether delphinidin induces the release of miR-23a-3p encapsulated in EVs from intestinal cells and whether these EVs increase miR-23a-3p expression in skeletal muscle cells. A single dose of delphinidin increased the expression of miR-23a-3p in the small intestine of mice. To examine whether delphinidin affects the secretion of miR-23a-3p in intestinal cells, we used differentiated Caco-2 cells as an in vitro model. Results showed that delphinidin increases the expression of miR-23a-3p in EVs secreted from differentiated Caco-2 cells. In addition, EVs derived from delphinidin-treated Caco-2 cells were taken up by differentiated C2C12 myotubes, resulting in increased intracellular miR-23a-3p expression. Our in vitro results suggest that intestinal cell-derived EVs may contribute to the antimuscle atrophy activity of delphinidin through the delivery of miR-23a-3p to skeletal muscle cells.