Hyperforin is a major active constituent of Hypericum perforatum L. extract, which is widely used for the treatment of
depressive disorders. Recent studies have reported that
hyperforin reduced
inflammation in
stroke and suppressed proliferation and differentiation in keratinocytes.
Psoriasis is a chronic immune-mediated inflammatory
skin disease in which the IL-23/IL-17 axis plays an important role. To investigate the underlying inflammatory mechanisms and response of
hyperforin in
psoriasis, we use
imiquimod (IMQ)-induced mice model, in vitro cultured murine splenic γδ T cells, and HaCaT cells in this study. Data showed that
hyperforin reduced epidermal thickness and decreased IMQ-induced pathological scores of cutaneous skin lesions in mice. Meanwhile we proved that
hyperforin suppressed infiltration of CD3+ T cells and downregulated expression of Il1,
Il6, Il23, Il17a, Il22,
antimicrobial peptides (AMPs) in the skin lesion.
Hyperforin significantly inhibited
imiquimod-induced
splenomegaly, reduced serum levels of TNF-α and
IL-6, and
IL-17A in splenocytes and draining lymph nodes. Our study also suggested that
hyperforin lessened the infiltration of γδ T cell and CCR6+ γδ T cells in spleen and lymph nodes.
Hyperforin also suppressed the typical
psoriasis-like inflammatory responses and the infiltration of IL-17A+ cells in dermal γδ T cells of IMQ treated Tcrd-/- mice transferred with γδ T cells. In vitro studies,
hyperforin reduced the expression and secretion of
IL-17A in γδ T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and γδ T cells. In conclusion,
hyperforin alleviates IMQ-induced
inflammation in
psoriasis through suppressing the immune responses exerted by
IL-17 A-producing γδ T cells and related
cytokines by modulating MAPK/STAT3 pathways. Our study provided a novel therapeutic tragedy for
psoriasis by which
hyperforin attenuates
psoriasis-related inflammatory responses.