Polysaccharides from Psoralea corylifolia seeds suppress osteoclastogenesis and alleviate osteoporosis

Psoralea corylifolia seeds, traditionally used in East Asia for their bone-strengthening properties, contain polysaccharides as one of their main components. However, the anti-osteoporotic potential of these polysaccharides remains underexplored. This study investigated the effects of polysaccharides extracted from P. corylifolia seeds (PCEP) on osteoclast differentiation and bone loss. PCEP effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. Chemical composition analysis revealed that PCEP is predominantly composed of glucose and galactose, along with uronic acids. Mechanistically, PCEP suppressed the expression of c-Fos and NFATc1 transcription factors, key regulators of osteoclast differentiation, and significantly inhibited RANKL-induced phosphorylation of JNK, p38, and ERK MAPKs and the degradation of IκBα, pathways involved in the induction of c-Fos and NFATc1. This inhibition downregulated osteoclast-specific marker genes, including Atp6v0d2, DC-STAMP, and CtsK. In an ovariectomized mouse model of estrogen deficiency, PCEP administration mitigated bone loss and reduced body weight gain and fat accumulation. These findings indicate that PCEP is a bioactive polysaccharide capable of inhibiting osteoclast differentiation and ameliorating bone loss associated with estrogen deficiency, highlighting its potential as a novel therapeutic agent for postmenopausal osteoporosis.