Immunomodulatory and Anti-psoriatic Effects of Herbal Formula SC-E1 on Imiquimod-induced Psoriasis in Mice

Background: Psoriasis is a chronic and relapsing inflammatory autoimmune skin disease. We recently reported that SC-E1 has various beneficial biological effects, including anti-inflammatory activity in an in vitro experimental study. Therefore, SC-E1 has been expected as complementary and alternative medicines for various inflammatory autoimmune skin diseases, including psoriasis. In this study, we investigated the potential anti-psoriatic effect of SC-E1 using an imiquimod (IMQ)-induced skin inflammation in mice and explored the mechanism underlying those actions. Methods: : Psoriatic dermatitis was induced by repeated challenges with IMQ on the backs of C57BL/6 mice. SC-E1 (250 mg/kg, 500 mg/kg, and 1000 mg/kg) was administered to the mice orally once a day by oral gavage needle for 5 days before and together with IMQ application for another 7 days (totally 12 days of treatment). The anti-psoriatic effects of SC-E1 were evaluated by dermatitis score, skin histology, and immunological parameters. In addition, the mechanisms responsible for the immunomodulatory effect of SC-E1 were examined using p38 MAPK, IκBα, and NF-κB. Results: : We found that SC-E1 (500 mg/kg) or SC-E1 (1000 mg/kg) pretreatment ameliorated the development of IMQ-induced skin inflammation in mice. Histological analysis revealed a reduction of epidermal thickening, hyperkeratosis, and inflammatory cell infiltration in SC-E1 (500 mg/kg) or SC-E1 (1000 mg/kg) pretreatment. Moreover, SC-E1 (500 mg/kg) or SC-E1 (1000 mg/kg) pretreatment effectively attenuated production of Th1 cytokines (TNF-a, IFN-g) and Th17 cytokines (IL-17A and IL-23) in the serum and dorsal skin induced by IMQ in mice. SC-E1 (500 mg/kg) or SC-E1 (1000 mg/kg) pretreatment also inhibited splenomegaly. In addition, SC-E1 inhibited the expression of inflammatory modulators, such as p38 MAPK, IκBα, and NF-κB in the skin of mice induced by IMQ. Conclusion: Our present study demonstrated that the immunomodulatory mechanism underlying the anti-psoriatic effect of SC-E1 on IMQ-induced in mice may be attributed to the inhibition of production of various systemic proinflammatory mediators via a mechanism that may involve the inhibition of MAPK and NF-κB signaling pathway. Based on the results we suggest that SC-E1 could be considered as an anti-psoriatic agent for the prevention or treatment of inflammatory autoimmune skin diseases including psoriasis.