| Eczema is an extremely common skin disease,a severe itchy skin inflammation caused by a variety of internal and external factors.Atopic dermatitis(AD)is a type of eczema that is extremely difficult to cure.It is clinically characterized by recurring eczema symptoms and intense itching,leading to skin peeling and susceptibility to skin infections.The current treatment drugs for AD include topical drugs(flucloxacillin,etc.)and related monoclonal antibody drugs(anti-IL-4 receptor antibody,etc.),these drugs all have therapeutic effects on AD,but they cannot achieve a comprehensive radical effect and are expensive,which brings a significant economic burden to patients.Mulgedium tataricum is a natural herb with anti-inflammatory,immune-regulating and anti-bacterial properties.Previous laboratory studies have shown that M.tataricum can be very effective in the treatment of autoimmune disease-psoriasis.Therefore,we speculate whether M.tataricum can also effectively treat atopic dermatitis? In order to test this idea,we first analyzed the active components of M.tataricum alcohol extract by HPLC-MS technology;Secondly,we constructed an AD mouse model and treated it with drugs to observe the changes of symptoms related to atopic dermatitis after the treatment with M.tataricum.And carring out experiments at the molecular and cellular levels,using RT-PCR,WB and other technologies to detect changes in AD-related factors,such as the classic AD pathway Th1/Th2 and other immune-related pathways.The relevant cells were then cultured,and the cell-level experiments were used to further confirm the molecular targets of M.tataricum in the treatment of atopic dermatitis.Through a series of experiments to determine whether the M.tataricum alcohol extract ointment has the effects of immune regulation and amelioration of itching symptoms on the body of atopic dermatitis.To explore the pharmacodynamic mechanism and molecular targets of M.tataricum in the treatment of atopic dermatitis,so as to further develop the efficacy of M.tataricum.Firstly,the main chemical components of the alcohol extract of M.tataricum were analyzed by HPLC-MScombined with the analysis of its molecular structure and molecular weight,and it was found that the main effective components of the alcohol extract of M.tataricum were Digonidone,Stigmasterol,Lettuce,Dandelion sterol,Apigenin and so on.Preliminary studies have found that the alcohol extract of M.tataricum can ameliorated the clinical symptoms of a mouse model of atopic dermatitis,including improvement of skin lesions,splenomegaly and spleen index reduction,and decreased serum Ig E expression.And the molecular mechanism of M.tataricum against atopic dermatitis has been further studied.Real-time PCR was used to detect the expression of some atopic dermatitis cytokines in mouse skin tissues,such as Th1,Th2,Th17 and other related factors of inflammatory cells.The results show that M.tataricum can effectively down-regulate the expression of key factors in Th2,for example: IL-4,IL-5,IL-12 and other factors.Secondly,M.tataricum significantly inhibited the expression of factors closely related to inflammation in Th17,such as IL-17 A,IL-17 F,IL-23 and so on.Moreover,M.tataricum can regulate the m RNA expression of pro-inflammatory cytokines such as keratinocyte-secreted factors IL-1,IL-36,TSLP and IL-33.At the same time,it down-regulated the protein expression levels of IL-4,IL-13,IL-17 A,IL-17 F and IL-1α.From the response of immune level,we can analyze the amelioration of the scabs,redness and bleeding caused by the excessive proliferation of the stratum corneum of the AD model.At the cellular level,it was verified that M.tataricum can effectively inhibit the abnormal proliferation of Ha Ca T cells in the inflammation model and effectively regulate the expression of pro-inflammatory factors such as IL-31,IL-33 and IL-1 secreted by keratinocytes.Therefore,it is inferred that M.tataricum extract may inhibit the expression of Th1,Th2,Th17 and IL-1 family factors,exerting anti-inflammatory effects.It mainly inhibits the secretion of inflammatory factors secreted by keratinocytes.In turn,it inhibits the occurrence of AD and inhibits the expression of Th2 and Th17-related factors downstream of AD pathogenesis,and exerts the efficacy of anti-atopic dermatitis and effectively ameliorating the clinical symptoms of atopic dermatitis.At the same time,studies have found that the alcohol extract of M.tataricum may reduce the itching behavior caused by atopic dermatitis.The results of the study showed that M.tataricum significantly inhibited the secretion of mast cells in skin tissues and reduced the content of Ig E in the serum,and M.tataricum significantly down-regulated the expression of IL-31 and TSLP m RNA and protein levels in mouse skin tissues.In order to further verify the anti-pruritic effect of M.tataricum,it was found that M.tataricum down-regulated the m RNA expression levels of PAR-2,TSLP,IL-33,IL-31 and TRPA1 in the dorsal root ganglia(DRG).It is indicated that M.tataricum can reduce the symptoms of itching in the AD model by inhibiting the abnormal activation of itching factors.At the cellular level,using inflammatory Ha Ca T cells,it was found that M.tataricum can directly inhibit the abnormal proliferation of inflammatory keratinocyte Ha Ca T,and it can significantly down-regulate the m RNA expression levels of IL-4,IL-33,IL-315 and TSLP in the cellular inflammation model.By inhibiting the abnormal secretion of TSLP and IL-31,M.tataricum blocks the transmission of the itch signal at the initial stage,thereby inhibiting the itch signal from being transmitted to the dorsal root ganglion and triggering the itch behavior.According to the research results,combined with the consistency of the results at the animal level and the cell level,it was shown that the alcohol extract of M.tataricum not only regulates the expression of related pro-inflammatory factors in the Th1,Th2,Th17 and IL-1 families,but also M.tataricum can inhibit the high expression of key itching mediators such as IL-31,TSLP,and PAR-2.Thereby,scratching caused by pruritus can be reduced,skin lesions and bleeding caused by scratching can be further improved,and the clinical characteristics of atopic dermatitis can be significantly ameliorated.Therefore,M.tataricum exerts a synergistic effect of anti-inflammatory and antipruritic effects on anti-atopic dermatitis.However,the coupling effect between pruritus and immune response needs further study.In conclusion,M.tataricum had obvious curative effect in inhibiting inflammation and reducing itching in atopic dermatitis,its molecular mechanism is related to the abnormal secretion of inflammatory factors in the pathogenesis of AD,such as IL-4 and IL-13 of Th2,IL-17 A and IL-23 of Th17,and pro-inflammatory factors in the IL-1family.Its mechanism of reducing itching is related to the secretion of TSLP and IL-31.Experiments at the cellular level confirmed that chicory effectively inhibited the proliferation of inflammatory cells and down-regulated the expression of related factors.Our findings suggest that M.tataricum acts synergistically on multiple molecular targets and signaling pathways in atopic dermatitis.It provides new ideas for the research and development of therapeutic drugs for atopic dermatitis,and lays a foundation for further development of the medicinal value of M.tataricum. |
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