Mechanisms of Guben Huashi Formula in the Treatment of DNCB-induced Atopic Dermatitis in Mice
Objective To explore the possible mechanism of Guben Huashi Formula in the treatment of atopic dermatitis(AD).Methods The binding ability between the active compound components of the Guben Huashi Formula and the filaggrin(FLG)and aromatic hydrocarbon receptor(AHR)was firstly analyzed by molecular docking,and subsequently further validated by the AD mouse models stimulated by 2,4-dinitrochlorobenzene(DNCB).After 28 days of continuous modeling and drug administration,the severity of skin lesions and transepidermal water loss(TEWL)were observed.HE staining was used to observe pathological tissues,number of itchy cycles,spleen index,and ear thickness in mice.The expression levels of skin barrier-related proteins and AHR,OVOL1 protein were detected by Western blot and immunohistochemistry.ELISA was used to detect serum levels of IgE,IL-13 and IL-22,and flow cytometry was used to detect the ratio of Th1,Th2 and Th17 to CD4+T cells subsets in lymph nodes.The Luminex method was used to detect various factor levels.Results The molecular docking results showed a strong binding ability between the target and the key compound components of Guben Huashi Formula.The results of animal experiments showed that,after treatment,the severity scores of skin lesions,TEWL,number of itching cycles and ear thickness were significantly decreased in the Guben Huashi group,as compared with the AD model group(P＜0.05),reduced the ratios of Th1,Th2,and Th17 in lymph nodes,and improved the levels of IgE,IL-13 and IL-22 in serum.After treatment,Guben Huashi Formula up-regulated the expression level of FLG,IVL,LOR,Occludin,AHR,and OVOL1 and significantly down-regulated the expression of IL-1β,IL-4,IL-5 and IL-33 compared with the AD model group(P＜0.05).Conclusion Guben Huashi Formula may promote skin barrier dysfunction and immune dysregulation,probably through the AHR/OVOL1/FLG axis,to achieve the effect of treating or inhibiting the progression of atopic dermatitis.
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维普
