Liu Wei, Song Wanci, Luo Yang, Dan Hanxiong, Li Li, Zhang Zhouyang, Zhou Daonian, You Pengtao
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
Post-doctoral Research Center of Mayinglong Pharmaceutical Group Co., Ltd., Wuhan, Hubei 430060, PR China.
Saudi Pharm J. 2022 Oct;30(10):1426-1434. doi: 10.1016/j.jsps.2022.07.003. Epub 2022 Jul 19.
Atopic dermatitis (AD), characterized by eczema as a chronic pruritic inflammatory skin disease, has become a serious health problem with recurrent clinical episodes. However, current clinical treatments have limited relief and are accompanied by adverse effects. Therefore, there is a necessity to develop new effective drugs for AD treatment. Angelica Yinzi (AYZ) is a classic ancient prescription for nourishing blood, moistening dryness, dispelling wind, and relieving itching. However, its mechanism for alleviating atopic dermatitis remains unknown. Therefore, this study aimed at determining the effects of AYZ and its potential mechanism in alleviating AD-like symptoms.
In the present study, we used 1-chloro-2,4-dinitrobenzene (DNCB) to establish a mouse model of atopic dermatitis, where DNCB readily penetrates the epidermis to cause inflammation. Histopathological analysis was performed to examine the thickening of dorsal skin and infiltration in the inflammatory and mast cells in C57BL/6 mice. Additionally, the immunoglobulin E (IgE) levels in serum were determined by enzyme-linked immunosorbent assay (ELISA) kits. The IL-1β and TNF-α expression were detected using qRT-PCR. Next, the Western blotting and immunohistochemistry assays were performed to assess the contribution of MAPKs/NF-κB signaling pathways and the NLRP3 inflammasome in AD responses.
Histopathological examination revealed that AYZ reduced the epidermal thickness of AD-like lesioned skin and repressed the infiltration of mast cells into AD-like lesioned skin. AYZ significantly decreased the phosphorylation of p38 MAPK, JNK, ERK and NF-κB and downregulated serum IgE levels and IL-1β and TNF-α mRNA levels. Additionally, the NLRP3, ASC, Caspase-1, and IL-1β expression in dorsal skin were effectively down-regulated following AYZ treatment ( < 0.05 and < 0.01).
These findings revealed that AYZ effectively suppressed AD-induced skin inflammation by inhibiting the activation of the NLRP3 inflammasome and the MAPKs/NF-kB signaling. Therefore, AYZ is a potential therapeutic agent against AD in the clinical setting.
特应性皮炎（AD）是一种以湿疹为特征的慢性瘙痒性炎症性皮肤病，临床反复发作，已成为一个严重的健康问题。然而，目前的临床治疗缓解效果有限且伴有不良反应。因此，有必要开发治疗AD的新型有效药物。当归饮子（AYZ）是一首养血润燥、祛风止痒的经典古方。然而，其缓解特应性皮炎的机制尚不清楚。因此，本研究旨在确定AYZ缓解AD样症状的作用及其潜在机制。
在本研究中，我们使用1-氯-2,4-二硝基苯（DNCB）建立特应性皮炎小鼠模型，DNCB可轻易穿透表皮引起炎症。对C57BL/6小鼠背部皮肤增厚情况以及炎症细胞和肥大细胞浸润情况进行组织病理学分析。此外，采用酶联免疫吸附测定（ELISA）试剂盒测定血清中免疫球蛋白E（IgE）水平。使用qRT-PCR检测白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达。接下来，进行蛋白质免疫印迹和免疫组织化学分析，以评估丝裂原活化蛋白激酶/核因子-κB（MAPKs/NF-κB）信号通路和NLRP3炎性小体在AD反应中的作用。
组织病理学检查显示，AYZ可减轻AD样皮损的表皮厚度，并抑制肥大细胞向AD样皮损皮肤浸润。AYZ显著降低p38丝裂原活化蛋白激酶、应激活化蛋白激酶（JNK）、细胞外调节蛋白激酶（ERK）和核因子-κB的磷酸化水平，下调血清IgE水平以及IL-1β和TNF-α mRNA水平。此外，AYZ治疗后，背部皮肤中NLRP3、凋亡相关斑点样蛋白（ASC）、半胱天冬酶-1（Caspase-1）和IL-1β的表达有效下调（P<0.05和P<0.01）。
这些研究结果表明，AYZ通过抑制NLRP3炎性小体和MAPKs/NF-κB信号通路的激活，有效抑制了AD诱导的皮肤炎症。因此，AYZ在临床上是一种潜在的抗AD治疗药物。
