Structural characterization and anti-osteoporosis effects of polysaccharide purified from Eucommia ulmoides Oliver cortex based on its modulation on bone metabolism

EuOCP3, with a molecular weight of 38.1 kDa, is an acidic polysaccharide purified from Eucommia ulmoides Oliver cortex. Herein, we determined that the main backbone of EuOCP3 was predominantly composed of →4)-α-GalpA-(1 → 4)-α-GalpA-(1→, →4)-α-GalpA-(1 → 5)-α-Araf-(1→, →4)-α-GalpA-(1 → 2)-α-Rhap-(1→, and →4)-α-GalpA-(1 → 5)-α-Araf-(1 → 2)-α-Rhap-(1 → repeating blocks, which were connected by →2,3,5)-α-Araf-(1→. The side chains, substituted at C-2 and C-5 of →2,3,5)-α-Araf-(1→, contained T-β-Araf→ and T-β-Araf → 4)-α-GalpA-(1 → residues. In dexamethasone (Dex)-induced osteoporosis (OP) mice, EuOCP3 treatment restored cortical bone thickness, increased mineralized bone area, enhanced the number of osteoblasts, and decreased the number of osteoclasts on the surface of cortical bone. Combining analysis of gut microflora, serum metabolite profiles, and biological detection results, we demonstrated that EuOCP3 regulated the abundance of specific species within the gut microflora, such as g_Dorea and g_Prevotella, and ameliorated oxidative stress. In turn, enhancement of osteogenic function and restoration of bone metabolism via the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway was indicated. The current findings contribute to understanding the potential of EuOCP3 in anti-OP treatment.