背景:传统的草药配方,Dang-Gui-Liu-HuangTang(DGLHT)先前已被证明可以抑制T淋巴细胞增殖并抑制树突状细胞功能。假设/目的:评估GLHT治疗银屑病的治疗价值,Th1和/或Th17细胞介导的炎症性皮肤病,并研究潜在的分子机制。
方法:采用咪喹莫特(IMQ)诱导的银屑病样炎症的体内小鼠模型来研究DHDHT的作用。在使用IL-1α的体外模型中检查了DGLHT(DGLHT-E)的乙醇提取物的抗炎作用及其机制,IL-17A,IL-22,制瘤素M,加上TNF-α(M5)刺激HaCaT细胞。通过分析IL-22刺激的HaCaT细胞中K16、K17和Ki67的表达水平来检查DGLHT-E的抗增殖作用。
结果:在IMQ处理的小鼠中,局部应用1%DGLHT-E可显着减少牛皮癣样症状,包括鳞屑和表皮增生。免疫组织化学研究表明,DGLHT-E通过抑制局部皮肤病变中IL-22的产生而发挥了有效的抗炎作用。DGLHT-E还通过抑制ERK1/2,JNK和STAT3信号通路来减弱M5刺激的HaCaT细胞中CXCL10和CCL20的产生。此外,盐酸小檗碱,GLHT-E的主要成分抑制IL-22刺激的HaCaT细胞中增殖标志物K16和K17的表达。
结论:这些结果表明,DGLHT-E为银屑病提供了一种可能的治疗方法,盐酸小檗碱可能是一种有用的成分软膏为基础的治疗银屑病病变。
BACKGROUND: The traditional herbal formula, Dang-Gui-Liu-Huang Tang (DGLHT) has been previously shown to inhibit T lymphocyte proliferation and suppress dendritic cell function. Hypothesis/Purpose: To assess the therapeutic value of DGLHT for the treatment of psoriasis, a Th1 and/or Th17 cell-mediated inflammatory skin disease, and to investigate the underlying molecular mechanisms.
METHODS: An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation was used to investigate the effect of DGLHT. The anti-inflammatory effects of an ethanolic extract of DGLHT (DGLHT-E) and the mechanism responsible were examined in an in vitro model using IL-1α, IL-17A, IL-22, oncostatin M, plus TNF-α (M5) stimulated HaCaT cells. The anti-proliferative effect of DGLHT-E was examined by analyzing the expression levels of K16, K17 and Ki67 in IL-22 stimulated HaCaT cells.
RESULTS: Topical application of 1% DGLHT-E significantly reduced psoriasis-like symptoms including scaling and epidermal hyperplasia in IMQ-treated mice. Immunohistochemical studies showed that DGLHT-E exerted potent anti-inflammatory effects by inhibiting IL-22 production in local skin lesions. DGLHT-E also attenuated the productions of CXCL10 and CCL20 in M5-stimulated HaCaT cells by suppressing the ERK1/2, JNK and STAT3 signaling pathways. Furthermore, berberine hydrochloride, a primary constituent of DGLHT-E inhibited the expressions of the proliferation markers K16 and K17 in IL-22 stimulated HaCaT cells.
CONCLUSIONS: These results suggested that DGLHT-E offers a possible treatment for psoriasis, and that berberine hydrochloride might be a useful component of ointment-based treatments for psoriatic lesions.