| Psoriasis is a kind of chronic inflammatory skin disease,which is affected by many factors such as genetics,diet and environment.The pathogenesis is not fully understood,and it is known that a variety of immune signaling pathways play a role.Fritillaria cirrhosa d.Don is a liliaceous perennial herbaceous plants,the bulb medicine more than two thousand years.Researchers have isolated and identified from Fritillaria cirrhosa with antitussive,asthmatic,expectorant,sedative,analgesic,anti-inflammatory,antibacterial,antioxidant,antitumor and other effects of alkaloids,sterols,polysaccharides,volatile oil and many other chemical components.Fritillaria cirrhosa has been included in the list of items that can be used for health food by the National Health Commission.As a therapeutic Chinese medicine,it is widely used for lung heat,dryness and cough,dry cough and other diseases.The metabolome was used to analyze the metabolites of Fritillaria cirrhosa,and the steroid sugar alkaloid Khasianine was found.In this study,Khasianine,an active component in Fritillaria cirrhosa,was used as the research object to systematically evaluate its improvement effect on IMQ-induced psoriatic-like inflammation in mouse models,and its effect on inflammatory cytokines was detected by TNF-α-induced keratinocyte Ha Ca T,and the mechanism of its action was elucidated.The results of this study may enable Khasianine to provide experimental data support in the treatment of psoriasis,which has certain practical significance and application value.Specific research contents and results are as follows:(1)The therapeutic effect of Khasianine on mice with psoriasis inflammation.Divided into 3 groups: Control group,IMQ group and Khasianine treatment group were treated with 5%imiquimod cream to establish a mice model of psoriatic inflammation.The thickening of the ear skin of mice was observed.The skin injury samples were stained with pathological sections to measure the thickness of the ear epidermis and detect the expression of related inflammatory factors,and the regulatory effect of Khasianine was evaluated at the animal level.The results showed that 1)Khasianine significantly improved the degree of lesions in IMQ-induced psoriasis mice,including scales,erythema and inflammatory cell infiltration.Compared with IMQ group,PASI score in treatment group was significantly decreased.2)Khasianine significantly improved the thickness of ear epidermis and ear layer;3)Khasianine could reduce the expression of CD4 and F4/80 at the skin lesions,indicating that Khasianine could significantly inhibit the infiltration of lymphocytes and macrophages.4)Khasianine effectively reduced the levels of TNF-α,p-p65,IL-17 A and IL-33 in mice skin lesions,suggesting that Khasianine may inhibit inflammation by inhibiting the production of TNF-α/NF-κB axis and pro-inflammatory factors in epidermal stratum corneum cells.(2)The effect of Khasianine on TNF-α-induced inflammatory response in Ha Ca T cells In this study,a TNF-α-induced inflammatory model of Ha Ca T cells was established.The effect of Khasianine on the nuclear factor NF-κB signaling pathway induced by TNF was detected by immunofluorescence method and Western blot.The results showed that p65 was mainly concentrated in the cytoplasm at resting state.When Ha Ca T cells were stimulated by TNF-α,the transfer of p65 from cytoplasm to nucleus was significantly observed,and the phosphorylation of p65 was inhibited by Khasianine.In addition,q RT-PCR and Western blot were used to detect the effect of Khasianine on TNF-α-induced inflammatory mediators secreted by Ha Ca T cells.The results showed that the expression of IL-17 A and IL-33 was greatly promoted by adding TNF-α to stimulate Ha Ca T cells,and the production of these inflammatory mediators was significantly inhibited by Khasianine.These results suggest that Khasianine exerts its anti-inflammatory effect by inhibiting the activation of NF-κB signaling pathway. |
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