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
摘要
Osteoarthritis is a musculoskeletal disease characterized by cartilage degradation and chronic pain, affecting approximately 7.6% of the global population in 2021. Passiflora edulis leaves contain bioactive compounds with potential for osteoarthritis treatment. Formulating P. edulis extract into chitosan nanoparticles can enhance its absorption, bioavailability, and efficacy. This study aimed to evaluate the anti-inflammatory and anti-osteoarthritis properties of P. edulis leaf nanoparticles (PLEN).
MethodsPLEN was evaluated for its anti-inflammatory activity in LPS-induced RAW 264.7 cells and anti-osteoarthritis effects on monosodium iodoacetate (MIA) induced rat model of osteoarthritis. Furthermore, previously identified P. edulis leaf compounds 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).
ResultsPLEN treatment demonstrated anti-inflammatory activity by inhibiting NO production by 43.68–60.58%, reducing iNOS levels by 11.98–38.83%, and decreasing TNF-α levels by 7.74–16.92%. In-vivo evaluation 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.
ConclusionThis study demonstrated that PLEN exerts anti-inflammatory and anti-osteoarthritis activities, and the results suggest different P. edulis bioactive compounds may target distinct anti-inflammatory and anti-osteoarthritis pathways.