Therapeutic effects of total coumarins from Urtica dentata Hand on collagen-induced arthritis in Balb/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Urtica dentata Hand (UDH), the root of Laportea bulbifera (Sieb. et. Zucc.) Wedd, has long been utilized in traditional Chinese medicine for the treatment of rheumatoid arthritis and some other autoimmune diseases. Coumarins are the main active principles contributing to UDH's efficacy, but the mechanisms have not been fully clarified.

AIM OF STUDY: To explore effects of total coumarins (TC) isolated from UDH on the development of type II collagen (CII)-induced arthritis (CIA) in Balb/c mice.

MATERIALS AND METHODS: Arthritis was induced in Balb/c mice by immunization with an emulsion of 200mg CII and complete Freund's adjuvant (CFA). The CIA mice were then given with a suspension of TC or saline by intragastric (i.g.) administration every other day. The incidence and severity of disease and histopathology of inflammation were assessed. Inflammatory response was determined by measuring the levels of different inflammation mediators in serum. The effect of TC on differentiation of CD4(+)CD25(+) Foxp3(+)Treg cells was examined by flow cytometry. The phenotype of bone marrow-derived dendritic cells (DCs), T-bet mRNA level and IL-12p70 secretion by DCs were also detected.

RESULTS: Pharmacologically, treatment with TC for type II collagen induced arthritis in mice through oral administration displayed significant and dose-dependent drop of clinical arthritis score and paw swelling, compared with the untreated CIA mice. Pathologic changes showed that TC protected tissues against bone destruction, whereas an almost complete destruction occurred in the CIA model group. The protective status was associated with a substantial decrease in the production of IFN-γ and IL-2, an increase of IL-10 and TGF-β and suppressive expression of T-bet in DCs. TC also induced the generation of CD4(+)CD25(+) Treg cells with a Treg phenotype Foxp3. TC-treated DCs were characterized as low expression of MHC class II and CD86 molecules, as well as a reduction of IL-12p70.

CONCLUSIONS: Our data suggest that TC provides substantial therapeutic protection against CIA by eliciting immune tolerance and it would be a valuable candidate for further investigation as a new anti-arthritic agent.