Mechanism and safety of triptolide in treatment of rheumatoid arthritis / 中草药

ABSTRACT

Objective: To explore the mechanism of triptolide in the treatment of rheumatoid arthritis (RA) and analyze its safety. Methods: A total of 60 rats were randomly divided into control group, model group, methotrexate (MTX) group and triptolide (TP) low, medium and high dose groups with 10 rats in each group. In addition to the control group, the rats in the other groups were established type II collagen-induced RA model. After the successful establishment of the model, rats in MTX group were given 0.4 mg/kg MTX by gavage from the 3rd week. Rats in TP high, middle, and low dose groups were given 0.1, 0.2, and 0.4 mg/kg TP by gavage. Rats in control group and model group were given equal volume distilled water once a day for 4 weeks. The paw swelling of rats in each group was compared. The percentage of CD4+CD25+and CD4+Foxp3+ Treg was detected by flow cytometry. The levels of IL-10, IL-17, TNF-α, VEGF, IFN-γ, TGF-β, ALT, and AST in the serum were detected. The pathological morphology of ankle joint was observed under microscope. The expression levels of IL-10, IL-17, TNF-alpha, VEGF, IFN-γ, and TGF-β were detected by immunohistochemistry. Results: Pathological sections showed that synovial cells were proliferated significantly in the ankle joint of rats in the model group, with infiltration of a large number of inflammatory cells such as monocytes and lymphocytes, new capillaries, thinning of bone trabeculae and serious erosion of cartilage surface. The degree of pathological changes in other groups was significantly less than that in model group. After treatment, the degree of joint swelling and arthritis index in MTX and TP groups were significantly decreased compared with those before treatment (P 0.05). There was no significant difference between MTX group and TP high dose group (P > 0.05). Conclusion: TP is effective in treating type II collagen-induced arthritis in rats, which can significantly improve joint swelling. Its mechanism is related to promoting the expression of IL-10 and TGF-β, increasing the proportion of Treg cells, inhibiting the expression of IL-17, TNF-α, VEGF and IFN-γ, and has no obvious hepatotoxicity.