Division of Cardiovascular Medicine, Taoyuan Armed Forces General Hospital, Taoyuan City 32551, Taiwan.
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
Int J Mol Sci. 2021 Jul 30;22(15):8237. doi: 10.3390/ijms22158237.
Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.
特应性皮炎（AD）是一种慢性持续性炎症性皮肤病，其特征为湿疹样皮损和瘙痒，已成为严重的健康问题。然而，常见的临床治疗方法提供的缓解效果有限，且伴有不良反应。因此，需要开发新型有效的疗法来治疗 AD。莲心碱是从成熟莲子的绿色胚中分离得到的小分子化合物（）。它具有双苄基异喹啉生物碱结构。相关研究表明，莲心碱具有多种药理和生物学活性，包括抗炎、抗血栓形成和抗糖尿病活性。然而，关于莲心碱在皮肤中的研究非常少，特别是其对炎症性皮肤病的相关作用。在本研究中，我们证明了它有潜力用于治疗特应性皮炎。通过体外研究，我们发现莲心碱抑制了 TNF-α/IFN-γ 刺激的人角质形成细胞（HaCaT）细胞中细胞因子和趋化因子的表达，并降低了 MAPK 和 NF-κB 信号通路的磷酸化。通过体内实验，我们使用 2,4-二硝基氯苯（DNCB）诱导小鼠模型中的特应性皮炎样皮肤炎症。结果表明，莲心碱显著减轻了 DNCB 诱导的皮肤屏障损伤、搔抓反应和表皮增生。它显著降低了经表皮水分丢失（TEWL）、红斑、血流和耳厚度，并增加了表面皮肤水合作用。此外，它还抑制了细胞因子的表达和信号通路的激活。这些结果表明，莲心碱作为治疗特应性皮炎或其他皮肤相关炎症性疾病的替代药物具有良好的潜力。
