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Abstract: Taurochenodeoxycholic acid (TCDCA) is one of the main bioactive substances of animals'' bile acid. In this study, we aimed to investigate the anti-arthritic effects and potential mechanism of TCDCA on adjuvant arthritis (AA) in rats. Freund''s complete adjuvant (FCA) was used to induce AA in rats. Paw swelling, index of thymus and spleen and body weight growth rate were measured, and polyarthritis index and radiologic changes were observed. The production of TNF-α, IL-1β, IL-6 and IL-10 was detected by ELISA in serum and synoviocytes. mRNA expression of TNF-α, IL-1β, IL-6 and IL-10 was determined by real-time RT-PCR in synovium tissue and synoviocytes. In both prophylactic and therapeutic treatment, TCDCA significantly suppressed paw swelling and polyarthritis index, increased the loss body weight and index of thymus and spleen, and amended radiologic changes in AA rats. The overproduction and mRNA expression of TNF-α, IL-1β and IL-6 were remarkably suppressed in serum and synovium tissue of all TCDCA-treated rats, however, IL-10 was markedly increased in prophylactic treatment. In a definite concentration ranging from 300μg/mL to 500μg/mL, TCDCA showed marked inhibition in the overproduction and mRNA expression of TNF-α, IL-1β and IL-6 in synoviocytes in a concentration-dependent manner, but opposite action on IL-10. In conclusion, treatment with TCDCA confers a good anti-adjuvant arthritis activity in rats, which its reparative effects could be mediated via reduction of the protein and mRNA expression of TNF-α, IL-1β and IL-6, and augment of IL-10 in rats. [Copyright &y& Elsevier]

Abstract: Recent evidences have suggested that the paucity of the apoptosis of fibroblast-like synoviocytes (FLS) may contribute to the pathogenesis of rheumatoid arthritis. Apoptosis induction of rheumatoid arthritis FLS is therefore suggested as a potential therapeutic approach for rheumatoid arthritis. Taurochenodeoxycholic acid (TCDCA), one of the main bioactive substances of animals' bile acid, could favorably ameliorate the progression development and bone destruction of adjuvant arthritis in rat. In this study, we aimed to investigate the possible effect of TCDCA on apoptosis induction of adjuvant arthritis FLS and the mechanisms involved in this process. Apoptosis was determined by flow cytometric analysis. Gene expression levels and the activities of caspase-3 and caspase-8 were evaluated using real time RT-PCR and luminogenic substrates. The activity of nuclear factor-κB (NF-κB) was measured by ELISA. The results showed TCDCA significantly enhanced the apoptosis of adjuvant arthritis FLS in a dose-dependent manner. Besides, TCDCA treatment markedly increased the gene expression level and activity of both caspase-3 and caspase-8. It could suppress the DNA-biding activity of NF-κB. We concluded TCDCA represented an apoptotic effect on adjuvant arthritis FLS via the activation of caspase cascade and this process may be mediated by NF-κB signaling pathway. It was suggested that TCDCA may be a potential therapeutic agent for rheumatoid arthritis. [Copyright &y& Elsevier]

Abstract: Context: Currently, there is a dramatically growing interest in Chinese traditional medicines, especially in the therapy of inflammatory diseases. Taurocholic acid (TCA), as a kind of natural bioactive substance of animal bile acid, has medicinal applications to treat a wide range of inflammatory diseases. Objective: The study was designed to evaluate the effects of TCA on cytokine secretion, such as TNF-α and IL-1β and on the ratio of CD4+/CD8+, which is beneficial for understanding the mechanism of TCA on immunoregulation preliminarily, and also will benefit our further research. Materials and methods: The gene and protein expressions of TNF-α and IL-1β were measured by real time RT-PCR and ELISA in serum, spleen and lymphocytes respectively. The ratio of CD4+/CD8+ in peripheral blood and lymphocytes was measured by flow cytometry. Results: Our present study has shown that lipopolysaccharide (LPS) and cyclosporin A (CsA) could increase or decrease the gene and protein expressions of TNF-α and IL-1β respectively. TCA (0.25g/kg, 0.125g/kg) could recover the suppressed expressions of TNF-α and IL-1β and increase the ratio of CD4+/CD8+. In vitro, TCA (15μg/mL) could inhibit the increased production of TNF-α and IL-1β; TCA (0.15μg/mL–15μg/mL) could inhibit the increased gene expressions of IL-1β and TNF-α. TCA (0.15μg/mL) could recover the suppressed expressions of TNF-α and IL-1β. Conclusion: The function of immunoregulation of TCA may be accomplished through modulating the gene and protein expressions of TNF-α and IL-1β and elevating CD4+/CD8+ T-cell ratio. [Copyright &y& Elsevier]