α-glucosyl-rutin activates immediate early genes in human induced pluripotent stem cells

Rutin is a natural flavonoid glycoside found in several vegetables and fruits such as buckwheat and onion. Rutin has a range of pharmacological effects that include anti-oxidant, anti-inflammation, anti-bacterial, and anti-cancer activities. α-glucosyl-rutin (AGR) is a derivative of rutin with increased water solubility that is used in cosmetics and foods. However, the effects of AGR on cellular responses have not been clarified, especially in stem cells. Induced pluripotent stem cells (iPSCs) show high proliferative activity and pluripotency; however, regulation of molecular machinery such as cell cycle, metabolism, and DNA repair differs between iPSCs and somatic cells. Here, we compared the effects of AGR on iPSCs and differentiated cells (fibroblasts and skin keratinocytes). AGR-treated iPSCs exhibited increased cell viability. RNA sequencing and reverse transcriptase PCR analysis revealed that AGR induced expression of immediate early genes (IEGs) and differentiation-related genes in iPSCs. Our results suggest that AGR may activate differentiation signals mediated by IEG responses in iPSCs, resulting in altered metabolic activity and increased cell viability.