A Rutin-Glycyrrhizic Acid Self-Assembled Nanohydrogel Promotes Early Osteogenic Differentiation Potential and Antioxidant Activity via Synergistic Inhibition of the IL-1β/NF-κB Axis.
Abstract
Plant-derived natural compounds have gained increasing attention in biomaterial development due to their intrinsic bioactivity and favorable biocompatibility. The anti-inflammatory, antioxidant, and osteogenic properties of rutin and glycyrrhizic acid have rendered them increasingly attractive candidates for therapeutic biomaterial development. However, their poor bioavailability significantly restricts their broad biomedical applications. Inspired by a supramolecular self-assembly strategy, we successfully constructed a rutin-glycyrrhizic acid nanohydrogel (RU-GA). The microstructure and formation mechanism were investigated through experimental characterization and computational simulations. Rutin (RU) and glycyrrhizic acid (GA) self-assemble into a carrier-free hydrogel in aqueous solution via hydrogen bonding and π-π stacking interactions, exhibiting favorable injectability, shapeability, and stability. RU-GA can disperse in water and release rutin-glycyrrhizic acid nanoparticles (RG NPs) with homogeneous particle sizes, while the hydrogel material possesses degradation and sustained-release properties. The bioavailability of RU and GA is synergistically improved through size effects and continuous release. Notably, the RU-GA hydrogel significantly promotes antioxidant activity and early osteogenic differentiation potential relative to the individual monomer components. Bioinformatics analysis further suggested that these bioactivities are associated with IL1B. Il1b knockdown experiments validated that RU and GA may synergistically suppress IL-1β-mediated NF-κB activation, thereby reducing oxidative stress and enhancing early osteogenic differentiation potential. Collectively, the rutin-glycyrrhizic acid nanohydrogel (RU-GA) represents a promising functional biomaterial, providing a strategy for the broad application of natural compounds in biomedical and related fields.
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