Neoagarohexaose Attenuates Inflammatory and Oxidative Joint Injury in MIA/CIOA Mouse Models of Osteoarthritis

Osteoarthritis (OA) is a prevalent chronic joint disease lacking disease-modifying drugs. Animal models with distinct pathogenic mechanisms—monosodium iodoacetate (MIA) for metabolic toxicity and collagenase-induced osteoarthritis (CIOA) for matrix degradation—are essential for therapeutic evaluation. In this study, topical application of neoagarohexaose (NA6) at 5 and 10 mg/kg twice daily was assessed in MIA- and CIOA-induced mouse OA models. NA6 at both doses reduced paw swelling, improved serum oxidative stress markers (catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO)), ameliorated cartilage damage and Osteoarthritis Research Society International (OARSI) scores, and decreased inflammatory cell infiltration. Immunohistochemistry showed that NA6 downregulated interleukin-1β (IL-1β) and interleukin-6 (IL-6), upregulated NAD(P)H:quinone oxidoreductase 1 (NQO1), and restored the compensatorily elevated heme oxygenase-1 (HO-1) toward baseline levels. The high-dose NA6 (10 mg/kg) showed comparable or favorable efficacy at the tested doses relative to the positive control diclofenac. These results demonstrate that NA6 exerts anti-inflammatory, antioxidant, and chondroprotective effects in both OA models, supporting its potential as a topical therapeutic candidate for OA symptom management and structural protection.