A self-assembled Dendrobium polysaccharide hydrogel with anti-aging activity via the FOXO signaling pathway.

Faced with the complexity and diversity of skin aging, it is critical to investigate multi-target synergistic anti-aging products. Herein, a novel composite hydrogel with anti-aging activity was developed based on Dendrobium polysaccharide, hyaluronic acid (HA), and nicotinamide (NMN). The hydrogen bond and van der Waals force were the main driving forces in the self-assembly interaction between Dendrobium polysaccharides (DDAM-1 and DOMOS), HA, and NMN. They also were important molecular mechanisms for the gel formation of the composite hydrogel, and the results have been confirmed by ITC and molecular docking. The composite hydrogel demonstrated potent anti-aging effect on the skin in vivo and in vitro, including inhibited elastase/collagenase, promoted type I collagen secretion, prevented ROS, and reduced the expression of IL-6/MMP-3. In addition, the anti-aging mechanism of the composite hydrogel may be associated with FOXO and TGF-β/Smad- SIRT1 signaling pathways mediated by FOXO3, SIRT1, SMAD3 and TGF-β. Briefly, this study demonstrates the potential of HA-infused composite hydrogels for use as anti-aging cosmetic products due to their synergistic anti-aging strategies for anti-aging applications.