ReferenceID 5467
Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A-Producing γδ T Cells
Front Immunol
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
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- Reference Id
- 5467
- Evidence Id
- 22057
- Core Evidence Id
- 22057
- Source Reference Id
- 4183
- Herb2 Reference Id
- HBREF004980
- Subject Paper Key
- HBIN029826_34025642
- Pubmed Id
- 34025642
- Doi
- 10.3389/fimmu.2021.635076
- Paper Title
- Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A-Producing γδ T Cells
- Paper Abstract
- 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 gammadelta 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-alpha and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of gammadelta T cell and CCR6+ gammadelta 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 gammadelta T cells of IMQ treated Tcrd -/- mice transferred with gammadelta T cells. In vitro studies, hyperforin reduced the expression and secretion of IL-17A in gammadelta T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and gammadelta T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing gammadelta 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.
- Journal
- Front Immunol
- Publish Year
- 2021
- Experiment Subject
- mouse; human; hacat cells; human keratinocyte hacat cells; in vitro cultured murine splenic gammadelta t cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Stroke; Psoriasis; Depressive Disorders; Cutaneous Skin Lesions; Chronic Immune-mediated Inflammatory Skin Disease; Imiquimod-induced Splenomegaly; Imiquimod
- Paper Title Cn
- Paper Title En
- Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A-Producing γδ T Cells
- Bilingual Status
- semi_complete