Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that substantially affects a patient’s quality of life. While steroids are the most common therapy used to temporally alleviate the symptoms of AD, effective and nontoxic alternatives are urgently needed. In this study, we utilized a natural, plant-derived phenolic compound, phloretin, to treat allergic contact dermatitis (ACD) on the dorsal skin of mice. In addition, the effectiveness of phloretin was evaluated using a mouse model of ACD triggered by 2,4-dinitrochlorobenzene (DNCB). In our experimental setting, phloretin was orally administered to BALB/c mice for 21 consecutive days, and then, the lesions were examined histologically. Our data revealed that phloretin reduced the process of epidermal thickening and decreased the infiltration of mast cells into the lesion regions, subsequently reducing the levels of histamine and the pro-inflammatory cytokines interleukin (IL)-6, IL-4, thymic stromal lymphopoietin (TSLP), interferon-γ (IFN-γ) and IL-17A in the serum. These changes were associated with lower serum levels after phloretin treatment. In addition, we observed that the mitogen-activated protein kinase (MAPK) and NF-κB pathways in the dermal tissues of the phloretin-treated rodents were suppressed compared to those in the AD-like skin regions. Furthermore, phloretin appeared to limit the overproliferation of splenocytes in response to DNCB stimulation, reducing the number of IFN-γ-, IL-4-, and IL-17A-producing CD4⁺ T cells in the spleen back to their normal ranges. Taken together, we discovered a new therapeutic role of phloretin using a mouse model of DNCB-induced ACD, as shown by the alleviated AD-like symptoms and the reversed immunopathological effects. Therefore, we believe that phloretin has the potential to be utilized as an alternative therapeutic agent for treating AD.

特应性皮炎（AD）是一种皮肤的慢性炎症性疾病，会严重影响患者的生活质量。虽然类固醇是用于暂时缓解AD症状的最常用疗法，但迫切需要有效且无毒的替代方法。在这项研究中，我们利用了一种天然的植物来源的酚类化合物–芦丁，来治疗小鼠背部皮肤上的过敏性接触性皮炎（ACD）。此外，使用2,4-二硝基氯苯（DNCB）触发的ACD小鼠模型评估了促肾上腺皮质激素的有效性。在我们的实验环境中，连续21天对BALB / c小鼠口服给予了促肾上腺皮质激素，然后进行了组织学检查。我们的数据显示，促视紫红质减少了表皮增厚的过程，并减少了肥大细胞向病变区域的浸润，随后降低血清中的组胺和促炎细胞因子白介素（IL）-6，IL-4，胸腺基质淋巴细胞生成素（TSLP），干扰素-γ（IFN-γ）和IL-17A的水平。这些变化与phloretin治疗后的血清水平降低有关。此外，我们观察到，与经AD类皮肤治疗的啮齿类动物相比，用促黄体素治疗的啮齿动物的皮肤组织中的促分裂原活化蛋白激酶（MAPK）和NF-κB途径受到抑制。此外，phloretin似乎限制了DNCB刺激引起的脾细胞过度增殖，从而减少了产生IFN-γ-，IL-4-和IL-17A的CD4的数量。这些变化与phloretin治疗后的血清水平降低有关。此外，我们观察到，与经AD类皮肤治疗的啮齿类动物相比，用促黄体素治疗的啮齿动物的皮肤组织中的促分裂原活化蛋白激酶（MAPK）和NF-κB途径受到抑制。此外，phloretin似乎限制了DNCB刺激引起的脾细胞过度增殖，从而减少了产生IFN-γ-，IL-4-和IL-17A的CD4的数量。这些变化与phloretin治疗后的血清水平降低有关。此外，我们观察到，与经AD类皮肤治疗的啮齿类动物相比，用促黄体素治疗的啮齿动物的皮肤组织中的促分裂原活化蛋白激酶（MAPK）和NF-κB途径受到抑制。此外，phloretin似乎限制了DNCB刺激引起的脾细胞过度增殖，从而减少了产生IFN-γ-，IL-4-和IL-17A的CD4的数量。⁺ T细胞在脾恢复到正常范围。两者合计，我们发现使用DNCB诱导的ACD的小鼠模型，促肾上腺皮质激素具有新的治疗作用，如减轻的AD样症状和逆转的免疫病理作用所示。因此，我们认为，促肾上腺皮质激素有潜力被用作治疗AD的替代治疗剂。