Passiflora edulis Sims leaves nanoparticle alleviates inflammation and osteoarthritis by suppressing pro-inflammatory cytokines production and matrix metalloproteinase-9: A combined in-silico, in-vitro, and in-vivo models

Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degradation and chronic pain, affecting 7.6% of the global population in 2021. Passiflora edulis leaf contains bioactive compounds with potential for OA medication. Formulating P. edulis into chitosan nanoparticles can enhance absorption, bioavailability, and efficacy. This study aims to evaluate anti-inflammation and anti-OA properties of P. edulis leaf nanoparticles (PLEN). PLEN was evaluated for its anti-inflammation activity on LPS-induced RAW 264.7 cells and anti-OA monosodium iodoacetate (MIA) induced rats OA model. Furthermore, P. edulis leaves compounds identified from previous studies were subjected to molecular docking against iNOS (PDB ID: 3E6T), TNF-α (PDB ID: 7KP8), IL-6 (PDB ID: 7DC8), and MMP-9 (PDB ID: 4XCT) receptors. PLEN treatment demonstrated anti-inflammation activity by inhibiting NO production by 43.68–60.58%, iNOS concentration by 11.98–38.83%, and decreasing TNF-α concentration by 7.74–16.92%. In-vivo test showed that PLEN increased body weight, reduced knee oedema, spleen weight, inflammation, and cartilage degradation. Molecular docking of P. edulis bioactive compounds revealed that cyclopassifloside II exhibited the highest iNOS inhibition with a docking score of -113.083 kcal/mol, N-cis-feruloyltyramine inhibited TNF-α with a docking score of -115.021 kcal/mol, cyclopassifloside XII inhibited IL-6 with a docking score of -116.875 kcal/mol, and Luteolin-6-C-fucoside inhibited MMP-9 with a docking score of -122.91 kcal/mol. In conclusion, this study demonstrated that PLEN exerts anti-inflammation and anti-OA activities and suggesting different groups of P. edulis bioactive compounds targeting distinct anti-inflammation and anti-OA pathways.