Comparative the effects of palm tocotrienol mixture and alpha-tocopherol on joint health and wnt signalling pathway in male rats with osteoarthritis induced by monosodium iodoacetate

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterised by cartilage deterioration, pain, and functional impairment. Both tocotrienol mixtures and a- tocopherol have been suggested to exert protective effects against OA. However, the higher cost of tocotrienol mixtures necessitates direct comparison with a-tocopherol to justify its use. This study aimed to compare the efficacy of palm tocotrienol mixture and a-tocopherol in a monosodium iodoacetate (MIA)-induced rat model of OA and to evaluate their effects on joint function, cartilage histology, and Wnt signalling. Three- month-old male Sprague-Dawley rats (~250 g) were randomly assigned to a normal control (sham) group, an OA group, a glucosamine sulphate group (250 mg/kg/day), a palm tocotrienol mixture group (100 mg/kg/day), or an a-tocopherol group (100 mg/kg/day). OA was induced by intra-articular injection of MIA in all groups except the sham group before the treatments commenced. The normal control and OA groups received drinking water throughout the experimental period, whereas the treatment groups received their respective oral treatments for four weeks. Throughout the treatment period, joint function was assessed weekly using rats' rearing activity, digital grip strength, and inverted-mesh wire tests. Following euthanasia and joint harvest, cartilage integrity was evaluated by histological analysis, while molecular changes in the cartilage layer were examined using quantitative real-time PCR and Western blot analysis. The study found that the OA group exhibited significant functional impairment (increased joint width and loss of grip strength) and cartilage degeneration (Mankin's structural score) compared with the sham group (p<0.05). Palm tocotrienol improved cartilage histology and reduced Mmp13 and Illb gene expression, while most Wnt- related markers showed limited changes at the study endpoint (p<0.05). However, a- tocopherol upregulated Sost (p<0.05 vs all other groups) and Mmp13 mRNA expression (p<0.05 vs OA), whereas these changes were not observed in the palm tocotrienol group. In conclusion, palm tocotrienol and a-tocopherol showed different effects in rats with MIA-induced OA. Palm tocotrienol was associated with better preservation of cartilage structure, improved joint function, and lower Mmp13 gene expression, whereas a-tocopherol showed a more noticeable effect on Sost gene expression. These findings suggest that the two vitamin E isomers may influence OA through different mechanisms. Further studies are needed to better understand these mechanisms and their potential role in OA management.