Structural Characterization of Chondroitin Sulfate from Hybrid Sturgeon (Acipenser schrenckii × Huso dauricus) Cartilage and Its Alleviating Effect on Osteoarthritis

Objectives: Given that the structure-activity relationship between sturgeon chondroitin sulfate (S-CS) and the alleviation of osteoarthritis (OA) remains unclear, we characterized the structure of S-CS and explored the relationship between its structure and its effect in alleviating OA. Methods: Chondroitin sulfate was extracted from sturgeon cartilage by alcohol precipitation. Its structure was thoroughly characterized using infrared spectroscopy, pre-column derivatization, high-performance liquid chromatography with PMP (PMP-HPLC), nuclear magnetic resonance spectroscopy (NMR), and other techniques. A rat OA model was established to explore the mechanism underlying its alleviation of OA. In addition, 16S rRNA sequencing was performed to investigate the role of gut microbiota. Results: S-CS was identified as a sulfated polysaccharide with an average molecular weight of 68.81 kDa and a GlcUA-to-GalN molar ratio of approximately 1:1. NMR analysis confirmed its characteristic 6-/4-sulfation patterns. Oral administration of S-CS at 100 mg/kg/d significantly alleviated joint damage by inhibiting the NF-κB and p38 MAPK signaling pathways. Specifically, S-CS decreased the levels of p65 and p38 by 18.94% and 52.40% (p < 0.05), respectively, and decreased TNF-α concentration. Moreover, 16S rRNA sequencing showed that S-CS enhanced the diversity and richness of gut microbiota and reconstructed the microbial community structure. Conclusions: S-CS may be an effective supplement for OA.