Lycium barbarum polysaccharide alleviates osteoarthritis progression in mice DMM model by inhibiting chondrocytes ferroptosis and promoting the gut Lactobacillus/Alistipes ratio.

Abstract

BACKGROUND: Lycium barbarum polysaccharides (LBP) are natural polysaccharides compounds with multiple biological activities. Both ferroptosis, a form of cell death, and gut microbiota are involved in the pathological process of osteoarthritis (OA). The effects and mechanisms of LBP on chondrocyte ferroptosis, gut microbiota, and cartilage degradation are still unclear. METHODS: We evaluated the effects of LBP on cell activity through CCK8 assay. Iron ion content assay, iron staining, lipid peroxidation probe C11-BODIPY assay, malondialdehyde (MDA) assay and glutathione (GSH) content assay were used to evaluate the degree of ferroptosis. Ferroptosis-related proteins were tested by Western blot and immunofluorescence. The protective effect of LBP on cartilage damage and gut microbiota/metabolome was evaluated in the destabilization of medial meniscus (DMM)-induced OA model of mice. RESULTS: LBP reversed Erastin-induced ferroptosis and the effects of Erastin/IL-1β on chondrocyte anabolic/catabolic metabolism. LBP reduced the protein level of KEAP1 and increased the protein level of Nrf2 in chondrocytes. In DMM model, LBP significantly alleviated the pathological process of cartilage damage, and promoted the gut Lactobacillus/Alistipes ratio. CONCLUSION: LBP alleviates OA in DMM model mice by inhibiting chondrocytes ferroptosis and promoting the gut Lactobacillus/Alistipes ratio, suggesting LBP as a promising therapeutic approach for OA.