Protective effect of yellow pond turtle (Mauremys mutica) peptides on cartilage in papain-induced knee osteoarthritis rats via mediating the NF-κB/iNOS-COX-2 pathway

Knee osteoarthritis (KOA) is a common chronic joint disorder worldwide. The water extracts of yellow pond turtle ( Mauremys mutica ) plastron can be used to repair bones and tendons, but the effect and mechanism of yellow pond turtle peptides (YPTP) on KOA is not clarified. This study aimed to explore the corresponding functional effect and anti-inflammatory activity of YPTP on cartilage in rats with papain-induced KOA by network pharmacology and animal experiments. The network pharmacology results showed that the top ten key target genes of YPTP on KOA included TNF , FPR2 , APP , AGTR2 , AGTR1 , STAT3 , NFKBIA , BDKRB2 , F2 , and BIRC2 , which were involved in multiple pathways associated with NF-κB signaling. Protein-protein interaction analysis demonstrated that the key targets of YPTP on KOA included COX-2 and iNOS. In addition, YPTP administration (75 and 150 mg/kg) on rats with papain-induced KOA was performed, and knee joint swelling, biomarkers, inflammatory factors, joint microstructure and joint components were assessed. Animal experiment results indicated that YPTP could decrease the expression of COX-2, iNOS and other inflammatory factors in the NF-κB signaling pathway. YPTP could also regulate the expression of MMP-3 and COLLII induced by inflammatory factors, thereby relieving joint pannus, cartilage damage and bone resorption. Our findings indicated that YPTP could inhibit the NF-κB/iNOS-COX-2 pathway and regulate the expression of MMP-3 and COLLII, thereby restricting cartilage degradation and synovial inflammation. This study may provide a theoretical guidance for the selective use of YPTP supplementation on health regulation in the future.