Qingre Qushi formula suppresses atopic dermatitis via a multi-target mechanism.
Qingre Qushi formula suppresses atopic dermatitis via a multi-target mechanism.
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DOI：
10.1016/j.jep.2023.116923
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发表时间：
2023-07
影响因子：
5.4
通讯作者：
Dong-ming Wang;Xin Ma;Zhi-Ao Xu;Pei-jun Ding;Wanquan Cai;Rui Li;Wu-Qing Wang;Xin Liu;Hui-Min Zhang
中科院分区：
文献类型：
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作者：
Dong-ming Wang;Xin Ma;Zhi-Ao Xu;Pei-jun Ding;Wanquan Cai;Rui Li;Wu-Qing Wang;Xin Liu;Hui-Min Zhang
民族药理学相关性本课题组前期研究表明清热祛湿方具有治疗特应性皮炎（AD）的作用，其作用机制可能与调节IL-33/ST 2信号通路有关。然而，AD的分子机制是复杂的，并且各种AD亚型对针对不同靶点的治疗反应更好。对皮炎评分、抓挠频率和组织学评价进行了规范性评价。采用ELISA法检测血清中IgE和IgG 1水平。采用ELISA和RT-PCR检测相关细胞因子的表达。用QRQS处理IL-17 A刺激的HaCaT细胞以评估mRNA和蛋白质表达。为了阐明其机制，进行了基于来自UPLC的活性成分的网络药理学分析。通过分子对接，我们评估QRQS的活性成分与潜在的targets.ResultsUsing超高效液相色谱法，177 QRQS中的活性成分之间的结合亲和力。网络药理学分析表明，活性成分的抗AD作用与IL-17信号通路及其相关靶点有关。FT小鼠的特征在于Th 17主导的免疫紊乱。QRQS改善AD样症状，降低皮炎评分和抓挠频率。QRQS治疗后，IL-17 A表达受到抑制，IL-17通路相关细胞因子下调。沿着Th 17分化的改变，QRQS抑制IL-4、IL-13和TNF-α的表达。QRQS还降低暴露于IL-17 A的HaCaT细胞中IL-6、IL-8和考克斯-2的表达。结论QRQS对AD具有多靶点的免疫调节作用，可通过调节IL-17 A信号通路改善Th 17为主的炎症反应。槲皮素、染料木黄酮、毛地黄黄酮和山奈酚是潜在的活性成分。
Ethnopharmacological relevanceOur previous studies have shown that the Qingre Qushi (QRQS) formula can treat atopic dermatitis (AD), and its possible mechanism is related to the regulation of the IL-33/ST2 signaling pathway. However, the molecular mechanism of AD is complex, and various AD subtypes respond better to therapies aimed at distinct targets.Aim of the studyThis study aimed to investigate the multi-target mechanism of QRQS using experimental and network pharmacology studies.Materials and methodsFlaky tail (FT) mice were treated with different concentrations of QRQS and cetirizine. The dermatitis score, scratching frequency, and histological evaluation were normatively evaluated. The levels of IgE and IgG1 in serum were tested using ELISAs. Using ELISA and RT-PCR, the expression of associated cytokines was determined. IL-17A-stimulated HaCaT cells were treated with QRQS to assess mRNA and protein expression. To elucidate the mechanism, a network pharmacology analysis based on active components derived from UPLC was conducted. Through molecular docking, we evaluated the binding affinity between the active constituents of QRQS and potential targets.ResultsUsing UPLC, 177 active ingredients in QRQS were identified. Network pharmacology analysis showed that the anti-AD effect of the active ingredients was related to the IL-17 signaling pathway and its related targets. FT mice are characterized by Th17-dominated immune disorders. QRQS ameliorated AD-like symptoms and decreased dermatitis scores and scratching frequencies. After QRQS treatment, IL-17A expression was inhibited and IL-17 pathway-associated cytokines were downregulated. Along with changes in Th17-differentiation, QRQS suppressed the expression of IL-4, IL-13, and TNF-α. QRQS also decreased the expression of IL-6, IL-8, and COX-2 in HaCaT cells exposed to IL-17A. The anti-AD active doses are 3.86 g/kg/day in vivo and 100 μg/mL in vitro.ConclusionQRQS has a multi-target immunoregulatory effect on AD and can improve the Th17-dominated inflammatory response by regulating the IL-17A signaling pathway. Quercetin, genistein, luteolin, and kaempferol are potential active ingredients.