Effect and Mechanism of Dihydroartemisinin on Rheumatoid Arthritis Animal Models / 中国实验方剂学杂志

ABSTRACT

Objective:To study the protective effect of dihydroartemisinin (DHA) on adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) in rats, in order to explore its possible mechanism. Method:Wistar rats were randomly divided into eight groups, namely AIA control group, AIA model group, AIA DHA group and AIA methotrexate group, CIA control group, CIA model group, CIA DHA group and CIA methotrexate group. To establish adjuvant-induced arthritis (AIA) model, rheumatoid arthritis rats were induced through intradermal injection with 0.1 mL Freund's complete adjuvant (FCA) into right postpedes except for the control group. To establish the model of collagen-induced arthritis (CIA), except for control group, the caudal root of rats was immunized subcutaneously with 0.2 mL of emulsion containing 1 g·L-1 of Collagen type Ⅱ (CⅡ). One week later, CⅡ emulsion was injected for the second time. After the rheumatoid arthritis model was successfully established and the administration with DHA (30 mg·kg-1·d-1), the anti-inflammatory effect of DHA on AIA/CIA rats was observed, including the arthritis index (AI), paw swelling degree and effect of DHA on immune organ index of AIA/CIA rats. Interleukin (IL)-6 levels in serum was detected by enzyme-linked immunosorbent assay (ELISA) and pathological sections of ankle joints of AIA/CIA rats. RAW264.7 macrophage cells were cultured in vitro and treated with DHA at various doses (0.5, 1, 2, 4, 8, 16 μmol·L-1) for 24 h, and the cell viability was detected by methyl thiazolyl tetrazolium(MTT) assay. Lipopolysaccharides (LPS) group, LPS+DHA groups (0.5, 1, 2 μmol·L-1) and control group were established. The level of IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). The protein expression levels of nuclear transcription factor-κB p65 (NF-κB p65) was tested by Western blot. Result:Compared with control group, the paw swelling, AI, spleen index and IL-6 levels of model group were significantly increased (PPPPPPPP-1) groups had a remarkable effect on the cell viability (PP-1. The level of IL-6 and the protein expression of NF-κB p65 in LPS group were higher than those of control group. Compared with LPS group, DHA (0.5 μmol·L-1) groups could significantly reduce the secretion of IL-6 (PκB p65. Conclusion:DHA can alleviate the ankle joint lesion on rheumatoid arthritis rats. Its mechanism may be related to NF-κB signal pathway.