Effect and Mechanism of Dihydroartemisinin on Rheumatoid Arthritis Animal Models
10.13422/j.cnki.syfjx.20191002
- VernacularTitle: 双氢青蒿素对两种类风湿关节炎模型的影响及机制
- Author:
Cheng-cheng DU
1
;
Yu-qing TAN
2
;
Jian-ying SHEN
2
;
Mei HUANG
1
;
Fang-ji GE
2
;
Kun HONG
2
;
Jian-hui SUN
2
;
Jun LUO
1
Author Information
1. School of Basic Medical Sciences, Guizhou Medical University, Guizhou 550025, China
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
- Publication Type:Research Article
- Keywords:
dihydroartemisinin;
adjuvant-induced arthritis;
collagen-induced arthritis;
mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(10):48-56
- CountryChina
- Language:Chinese
-
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 (P<0.01, P<0.05). DHA could significantly reduce paw swelling (P<0.05), arthritis score index (P<0.05), and spleen index (P<0.01), thymus index (P<0.05) and serum IL-6 level of AIA rats (P<0.05). But the spleen index of CIA rats was not decreased, while the thymus index and IL-6 level were decreased but not statistically significant. In addition, DHA can significantly improve the pathological changes of ankle, and decrease the pathological score on AIA/CIA rats (P<0.01). Compared with control group, DHA (4, 8, 16 μmol·L-1) groups had a remarkable effect on the cell viability (P<0.05, P<0.01). The safe medication range of DHA was less than 2 μmol·L-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 (P<0.05), and inhibit the expression of NF-κB p65. Conclusion:DHA can alleviate the ankle joint lesion on rheumatoid arthritis rats. Its mechanism may be related to NF-κB signal pathway.
