Effect And Mechanism Of Bisdemethoxycurcumin On Atopic Dermatitis

Background:Atopic dermatitis（AD）is a chronic and relapsing inflammatory skin disease characterized by chronic inflammation,skin-epidermal barrier damage,and immunoglobulin E（Ig E）-induced hyperresponsiveness to allergens,and produces cytokines mainly of Th2 type（IL-4,IL-5 and IL-13）.Due to the increasing incidence of AD year by year,it has become a major global health problem.The occurrence and recurrence of AD seriously affect people’s quality of life.At present,AD is an incurable chronic disease,and clinically,glucocorticoid treatment is mainly used with seriously side effects.Therefore,exploring the pathogenesis of AD and seeking effective strategy are urgent problems to be solved.Bisdemethoxycurcumin（BDMC）is an extract from the rhizome of traditional Chinese medicine turmeric.Compared with curcumin,it has better bioavailability and stability.Studies have shown that BDMC has pharmacological properties such as anti-inflammatory,anti-oxidative,anti-tumor and anti-proliferative activities,especially in allergic diseases such as allergic rhinitis,asthma,etc.,it has shown good pharmacological activity,but it has been used in atopic dermatitis.role has not yet been reported..Purpose:This study explored the improvement effect of BDMC on DNCB-induced AD mice,and conducted a preliminary study on its anti-AD mechanism;and this study conducted a preliminary study on the effect of BDMC on TNF-α/IFN-γ-induced HaCaT cells.Method:1.Effects of BDMC on DNCB-induced atopic dermatitis in mice32 BALB/C mice were randomly divided into 4 groups: Control group,AD group,AD+BDMC200（BDMC 200 mg/kg）and AD+BDMC400（BDMC 400 mg/kg）group.For the first 3 days after the start of the experiment,except for the Control group,the other 3 groups were sensitized with 150 μL or 30 μL of 1% DNCB in acetone-olive oil solution（3:1）respectively,on the back skin and the right ear.The dorsal skin and right ear of mice were respectively challenged with 150 μL or 30 μL of 0.5% DNCB solution once the other day,and meanwhile the test drug was orally administered daily for 5weeks.Materials were collected 24 hours after the last challenge.At the end of the experiment,observation indicators:（1）the number of scratches of the mice within10 min were observed and skin lesion was scored;（2）the spleen of the mice were harvested and weighed,and calculate the spleen index;（3）observe the skin lesions of mice by HE staining and toluidine blue staining Pathological changes;（4）ELISA was used to detect the levels of Ig E,IL-4 and IFN-γ in serum;（5）RT-q PCR was used to detect the levels of IL-1β,IL-4,IL-6 and TSLP in skin lesions.m RNA expression level;（6）Western blot was used to detect MAPK signaling pathway proteins（p-p38/p38,p-JNK/JNK）and NF-κB signaling pathway proteins（p-NF-κB/NF-κB,p-IκB/IκB）expression levels.2.Effects of BDMC on HaCaT cells induced by TNF-α/IFN-γHaCaT cells were divided into Control group,TNF-α/IFN-γ group,TNF-α/IFN-γ+BDMC15（BDMC 15 μM）and TNF-α/IFN-γ +BDMC30（BDMC 30 μM）group.Except for the Control group,other 3 groups were treated with TNF-α（10 ng/ml）and IFN-γ（10 ng/ml）for 24 h to establish an AD in vitro cell model,and were treated with drugs for 24 h at the same time.Detection indicators:（1）MTT assay to determine the effect of different concentrations of BDMC on HaCaT cell viability;（2）RT-q PCR method to detect the m RNA levels of IL-1β,IL-6,TARC,MDC and RANTES in HaCaT cells.Result:1.BDMC can significantly improve the symptoms of AD skin lesions induced by DNCB in BALB/C mice,reduce the number of scratches in mice,reduce spleen index,reduce inflammatory cell infiltration,and reduce epidermis and dermis thickness,reduce serum Ig E,IL-4 level,and increase IFN-γ level,inhibit the expression of inflammatory factors IL-1β,IL-4,IL-6,TSLP in skin lesions;reduce mast cell infiltration;BDMC can also reduce skin lesions.The expression of p-p38,p-JNK,and p-NF-κB protein in the medium increases the expression of p-IκB and inhibits the activation of MAPK and NF-κB signaling pathways.2.BDMC can inhibit the m RNA expression levels of IL-1β,IL-6,TARC,MDC and RANTES in HaCaT cells.Conclusion:The results show that BDMC can effectively relieve AD symptoms in mice,and the possible mechanism may be through inhibiting the abnormal activation of MAPK and NF-κB signaling pathways.In addition,BDMC can also significantly reduce the expression of inflammatory cytokines and chemokines in HaCaT cells,these results suggest that BDMC plays an important role in the treatment and prevention of AD.