Therapeutic Effect and Mechanism of Caulophyllum robustum Maxim Extract on Adjuvant Arthritis Rats

摘要

[Objectives]To study the anti-inflammation and anti-swelling effect of Caulophyllum robustum Maxim( CRM) extract on secondary lesions of adjuvant arthritis( AA),associated inflammatory factors of AA rats and mice immune function. [Methods]Rats were divided into high,middle and low dose CRM extract groups( 69. 23,34. 61,17. 31 mg/kg),methotrexate group( 0. 68 mg/kg),triptolide group( 7. 88 mg/kg),model group and normal control group. The AA rat model was induced by intradermal injection of Freund's complete adjuvant( FCA). After the AA model was established successfully,the paw swelling of AA rats was observed and recorded. The levels of interleukin-1β( IL-1β),interleukin-4( IL-4),interleukin-10( IL-10),Tumor Necrosis Factor-α( TNF-α),interleukin 17( IL-17),interferon( IFN-γ),granulocyte colony-stimulating factor( G-CSF) and transforming growth factor( TGF-β) in the serum of AA rats were detected by enzyme-linked immunosorbent assay( ELISA). The spleen was removed and weighed for detecting the drug influence on the immune organs.Impacts were observed by gavage administration at different dosages of 25 mg/kg,50 mg/kg,100 mg/kg for seven days,adopting carbon granules clearance test,delayed-type hypersensitivity induced by dinitrofluorobenzene( DNFB) coupled with flow cytometry evaluating lymphocytes( CD3^+,CD4^+,CD8^+) activation and serolysin test. [Results] Compared with the model group,the joint swelling,spleen index and inflammatory cytokines( IL-1β,IL-4,IL-10,TNF-α,IL-17,IFN-γ,G-CSF,TGF-β) were reduced significantly( P < 0. 05,P < 0. 01). And the activity of CRM was significantly superior to methotrexate and triptergium. Moreover,the results indicated that different dosages of 25 mg/kg,50 mg/kg,100 mg/kg of CRM could significantly reduce the carbon granules clearance index( K) and phagocytic index( a),inhibit the phagocytosis of mononuclear macrophages,reduce the mice swelling extent and inhibit DTH in mice induced by DNFB,decrease the quantity of serum hemolysin. Percentage of CD3^+,CD4^+,and the ratio of CD4^+,CD8^+ notably decreased,whereas CD8^+ obviously increased. Intragastrica dose of 50 mg/kg,100 mg/kg were acknowledged as more objective inhibiting effect compared with a dosage of 25 mg/kg.[Conclusions] Decreasing inflammatory cytokines content,non-specific immune,humoral immune and cellular immune function may be the therapeutic mechanism for rheumatoid arthritis( RA).