Lycium barbarum Polysaccharide Ameliorates Hindlimb Unloading‐Induced Bone Loss by Targeting Noggin

ABSTRACT Disuse bone loss is a common metabolic bone disease with limited effective, safe treatments. Lycium barbarum ( L. barbarum ), a traditional Chinese medicine and popular health food, has been historically noted in Ben Cao Gang Mu (Compendium of Materia Medica) for its bone‐strengthening properties. However, the effects of L. barbarum on disuse bone loss and the underlying mechanisms remain unclear. This study used a hindlimb‐unloading mouse model and a simulated microgravity model of MC3T3‐E1 cells in a rotary cell culture system to investigate the role of L. barbarum water extract (LBE) and polysaccharide (LBP). LBE and LBP significantly enhanced bone mass and strength in hindlimb‐unloaded mice. Further analysis identified a polysaccharide component, LBPP, as the active ingredient mediating these effects. LBPP enhanced osteoblast differentiation and ossification under normal conditions and promoted osteoblast activity under simulated microgravity. Mechanistic studies revealed that LBPP directly binds to noggin, a potent inhibitor of BMPs, facilitating phosphorylation of downstream Smads to stimulate bone formation. These findings demonstrate the potential of L. barbarum as a functional food for preventing disuse bone loss and provide a theoretical basis for its therapeutic applications.