Evaluating the Therapeutic Potential of <i>Hyriopsis cumingii</i> Polysaccharide in Osteoarthritis: Insights from a Mouse Model

Background: Hyriopsis cumingii polysaccharide (HCP) has been demonstrated to exhibit various biological activities. Our current research aimed to evaluate the protective effect of HCP on the osteoarthritis (OA) model mice. Methods: The therapeutic effect of HCP on OA was investigated by injecting monosodium iodoacetate into a mouse model of knee OA. The analgesic effect was assessed through behavioral analysis. The levels of serum antioxidant substances, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), as well as the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in articular cartilage, were measured by using enzyme-linked immunosorbent assay. The tissue morphology of articular cartilage was examined using hematoxylin–eosin and safranin O-fast green staining. Microcomputed tomography scans were employed to analyze the microstructure. Additionally, immunohistochemistry was utilized to detect the expression of type II collagen (COL2), matrix metalloproteinase (MMP)13, MMP3, IL-6, nuclear factor-kappa B (NF-κB), and TNF-α proteins in the articular cartilage. Additionally, the impact of HCP on gut microbiota (GM) was assessed through high-throughput fecal 16S ribosomal RNA sequencing. Results: The HCP significantly improved the gait of the mice; increased the levels of serum SOD, GSH-Px, and CAT; and reduced TNF-α and IL-6 in cartilage tissue. The surface of the articular cartilage appeared flat. Subchondral bone destruction was inhibited, and the bone volume fraction was significantly increased. The expression of COL2 was elevated, whereas the expressions of MMP13, MMP3, NF-κB, IL-6, and TNF-α were significantly decreased. HCP can also regulate the diversity of GM, increase the abundance of Firmicutes of GM, and significantly reduce the abundance of Bacteroidetes and Proteobacteria. The gram-negative and pathogenic phenotypes were downregulated in the low-, medium-, and high-dose HCP groups. Conclusions: HCP increases the levels of the body’s antioxidant factors, improves the morphology of cartilage tissue, and optimizes the microstructure of subchondral bone, thereby inhibiting the progression of OA. Therapeutic efficacy HCP may be associated with the regulation of GM.