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). Conclusions: 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.
Osteoarthritis (OA) is a degenerative joint condition with limited disease-modifying treatments currently. Palm tocotrienol-rich fraction (TRF) has been previously shown to be effective against OA, but its mechanism of action remains elusive. This study aims to compare serum metabolomic alteration in Sprague-Dawley rats with monosodium iodoacetate (MIA)-induced OA which were treated with palm TRF, glucosamine sulphate, or a combination of both. This study was performed on thirty adult male rats, which were divided into normal control (n = 6) and OA groups (n = 24). The OA group received intra-articular injections of MIA and daily oral treatments of refined olive oil (vehicle, n = 6), palm TRF (100 mg/kg, n = 6), glucosamine sulphate (250 mg/kg, n = 6), or a combination of TRF and glucosamine (n = 6) for four weeks. Serum was collected at the study's conclusion for metabolomic analysis. The findings revealed that MIA-induced OA influences amino acid metabolism, leading to changes in metabolites associated with the biosynthesis of phenylalanine, tyrosine and tryptophan as well as alterations in the metabolism of phenylalanine, tryptophan, arginine and proline. Supplementation with glucosamine sulphate, TRF, or both effectively reversed these metabolic changes induced by OA. The amelioration of metabolic effects induced by OA is linked to the therapeutic effects of TRF and glucosamine. However, it remains unclear whether these effects are direct or indirect in nature.