A modified system to promote stemness of mouse intestinal stem cells by activating Nrf2 and α2-adrenergic receptor signaling pathway

• Identified pVc and dexmedetomidine as synergistic enhancers of intestinal stem cell self-renewal via Nrf2 and α2-AR pathways. • Demonstrated that pVc acts through Nrf2-mediated antioxidant responses, while α2-AR activation suppresses cAMP signaling. • In vivo administration of these compounds enhances intestinal epithelial renewal and maintains stem cell positioning. • α2-AR activation promotes regeneration after radiation injury, suggesting therapeutic potential for intestinal damage.