Study On The Mechanism Of Daturae Flos Effective Fraction On Imiquimod-induced Psoriasis In Mice

A large number of studies have shown that psoriasis is an immune inflammatory skin disease mediated by T cells.The common lesion regions are located in the neck,back and extremities,accompanied by itching symptoms.Its characteristics of difficult radical treatment and easy recurrence bring great trouble to the daily life of patients with psoriasis.Daturae Flos is the dry flower of Datura metel L.of solanaceae plants.Previous studies showed that 70%ethanol extract of Daturae Flos was separated by macroporous adsorption resin column,and its 50%ethanol elution component was the effective fraction of Daturae Flos in the treatment of psoriasis.Clinical studies have confirmed that Daturae Flos effective fraction has a significant therapeutic effect on psoriasis,but at present,there are few reports about the more in-depth mechanism studies of immune and inflammatory regulation in the treatment of psoriasis.The purpose of this study is to study the pharmic efficacy and the relevant regulatory mechanism of the Daturae Flos effective fraction in the treatment of psoriasis,so as to further clarify the action mechanism of Daturae Flos effective fraction in the treatment of psoriasis.The specific research contents are as follows:1.The pharmacodynamic study of Daturae Flos effective fraction on psoriasis mice model.Daily use imiquimod to induce psoriasis like lesions in mice,intragastric administration of Daturae Flos effective fraction;use PASI scoring method to score the skin injury in mice back,the result showed that Daturae Flos effective fraction can significantly improve the appearance of skin lesions in psoriasis mice model induced by imiquimod,reduce the scale and skin thickness in lesioned skin region.HE staining was applied to observe the influence of Daturae Flos effective fraction on the skin histopathology of psoriasis mice model.The result showed that Daturae Flos effective fraction can significantly inhibit the over proliferation and incomplete keratosis of the epidermis cells in psoriasis mice model.Immunohistochemistry was applied to detect the influence of Daturae Flos effective fraction on the aggregation of CD4~+T lymphocytes,dendritic cells and neutrophils and the expression of Ki67,IL-17 and NF-?B in the skin of psoriasis mice model.The result showed that the Daturae Flos effective fraction can inhibit the aggregation of CD4~+T lymphocytes,neutrophils and dendritic cells and the expression of Ki67,IL-17 and NF-?B in the skin tissue.2.Study on the action mechanism of Daturae Flos effective fraction in the treatment of psoriasis.The differentially expressed genes between the skin of normal mice and the skin of psoriasis mice model were obtained by transcriptome sequencing,and then,the GO function analysis and KEGG pathway analysis of differentially expressed genes were performed to obtain the important signaling pathways in the pathogenesis of psoriasis mice model.The result showed that PI3K/AKT signaling pathway was an important pathway in the pathogenesis of psoriasis mice model induced by imiquimod;Western blot detected the effect of Daturae Flos effective fraction on the key signal factors of the PI3K/AKT signaling pathway.The results showed that Daturae Flos effective fraction could inhibit the phosphorylation of PI3K,AKT,mTOR and p70S6K and the expression of Fgf23 and VEGF.In conclusion,the Daturae Flos effective fraction has well therapeutic effect on the psoriasis mice model induced by imiquimod.Its action mechanism may be related to the intervention of the IL-23/IL-17inflammation axis and the inhibition of the PI3K/AKT signaling pathway and its downstream NF-?B and mTOR signaling pathways.This study revealed the action mechanism of Daturae Flos effective fraction in the treatment of psoriasis,and provided important scientific basis for the clinical application.