Yellow pond turtle peptides ameliorate inflammation and cartilage damage toxicity in papain-induced KOA rats by inhibiting COX-2 and iNOS expressions

Objective The drugs in the treatment of knee osteoarthritis (KOA) have significant side effects and poor effectiveness. The plastron of yellow pond turtles is rich in small peptides. As such, it might inform potentially possible to uptake and enhance KOA drug utilization. Nevertheless, the cartilage protective activity of yellow pond turtle peptides (YPTP) in KOA and associated mechanism have not been reported. Method We explored KOA rat cartilage protection mediated by YPTP, and its underlying mechanisms using network pharmacology (NP), animal experimentation, and molecular docking (MD) analyses. Results Based on our NP data, COX-2 and iNOS were the primary target proteins of YPTP in KOA. Using an animal model, we revealed that YPTP strongly suppressed contents of COX-2, iNOS, and MMP-3 while upregulating COL II to alleviate inflammation and minimize cartilage damage. In addition, MD analysis further validated the 5 YPTP-derived peptides that interacted with COX-2 and iNOS via hydrogen bonding and hydrophobic interactions. Of note, the reduced YPTP dose employed in this investigation enhanced IL-1beta contents in synovial membranes, which requires further exploration. Conclusion YPTP ameliorated inflammation and cartilage damage in papain-induced KOA rats by suppressing both COX-2 and iNOS expressions.