Divergent Effects of Palm Tocotrienol-Rich Mixture in Refined Olive Oil and Alpha-Tocopherol on Joint Health in a Rat Model of Osteoarthritis Induced with Monosodium Iodoacetate

Background/Objectives: Palm tocotrienol-rich mixture (PT) is a potential disease-modifying agent against osteoarthritis (OA), but direct comparisons with α-tocopherol (AT) are lacking. This study evaluated the joint-protective effects of PT versus AT in a monosodium iodoacetate (MIA)-induced rat model of OA. Methods: Male Sprague-Dawley rats (n = 6/group) received intra-articular MIA in the left knees to induce OA, followed by daily oral treatment with distilled water (OA control), glucosamine sulphate (250 mg/kg), AT (100 mg/kg), or PT (100 mg/kg, in refined olive oil) for four weeks. Non-OA rats receiving distilled water served as normal controls. Body weight, joint width, and grip strength were monitored weekly. Left knees were harvested for histological evaluation using Mankin scores. Cartilage lysates from the left knees were analysed for inflammatory cytokine and metalloproteinase gene expressions, along with protein phosphorylation ratios of β-catenin (Ctnnb) and nuclear factor kappa-B (Nfkb). Results: PT-treated rats showed no significant time-dependent deterioration in joint width or grip strength over the 4-week period. Histologically, PT significantly reduced cartilage structural degradation (p = 0.002 vs OA control) and downregulated Mmp13 mRNA expression (p < 0.05 vs OA control). Conversely, AT upregulated Il1b (p = 0.002 vs OA control; p = 0.010 vs normal control), Sost (p < 0.05 vs all OA groups), and Ctnnb (p = 0.010 vs OA control) mRNA expressions. However, no intergroup differences in phosphorylation of Ctnnb and Nfkb were observed (p > 0.05). Conclusion: PT is associated with a chondroprotective profile in MIA-induced OA rats, whereas AT is associated with a catabolic transcriptional pattern. Nevertheless, AT did not cause significant worsening of cartilage structure or activation of pathways under these conditions.