PDF(Pubmed)
Abstract：
Isoscopoletin is a compound derived from various plants traditionally used for the treatment of skin diseases. However, there have been no reported therapeutic effects of isoscopoletin on atopic dermatitis (AD). AD is a chronic inflammatory skin disease, and commonly used treatments have side effects; thus, there is a need to identify potential natural candidate substances. In this study, we aimed to investigate whether isoscopoletin regulates the inflammatory mediators associated with AD in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin treated RBL-2H3 cells. We determined the influence of isoscopoletin on cell viability through an MTT assay and investigated the production of inflammatory mediators using ELISA and RT-qPCR. Moreover, we analyzed the transcription factors that regulate inflammatory mediators using Western blots and ICC. The results showed that isoscopoletin did not affect cell viability below 40 μM in either HaCaT or RBL-2H3 cells. Isoscopoletin suppressed the production of TARC/CCL17, MDC/CCL22, MCP-1/CCL2, IL-8/CXCL8, and IL-1β in TNF-α/IFN-γ-treated HaCaT cells and IL-4 in PMA/ionomycin-treated RBL-2H3 cells. Furthermore, in TNF-α/IFN-γ-treated HaCaT cells, the phosphorylation of signaling pathways, including MAPK, NF-κB, STAT, and AKT/PKB, increased but was decreased by isoscopoletin. In PMA/ionomycin-treated RBL-2H3 cells, the activation of signaling pathways including PKC, MAPK, and AP-1 increased but was decreased by isoscopoletin. In summary, isoscopoletin reduced the production of inflammatory mediators by regulating upstream transcription factors in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin-treated RBL-2H3 cells. Therefore, we suggest that isoscopoletin has the potential for a therapeutic effect, particularly in skin inflammatory diseases such as AD, by targeting keratinocytes and basophils.
摘要：
Isoscobotetin是一种源自传统上用于治疗皮肤病的各种植物的化合物。然而,目前还没有报道异黄地素对特应性皮炎(AD)的治疗作用.AD是一种慢性炎症性皮肤病，常用的治疗方法有副作用；因此，有必要确定潜在的天然候选物质。在这项研究中,我们的目的是研究异种草素是否调节TNF-α/IFN-γ处理的HaCaT细胞和PMA/离子霉素处理的RBL-2H3细胞中与AD相关的炎症介质。我们通过MTT测定确定了异种酚对细胞活力的影响，并使用ELISA和RT-qPCR研究了炎症介质的产生。此外，我们使用Westernblots和ICC分析了调节炎症介质的转录因子.结果表明，在HaCaT或RBL-2H3细胞中，在40μM以下，异油菜素不会影响细胞活力。异双乙素抑制TNF-α/IFN-γ处理的HaCaT细胞和PMA/离子霉素处理的RBL-2H3细胞中TARC/CCL17，MDC/CCL22，MCP-1/CCL2，IL-8/CXCL8和IL-1β的产生。此外，在TNF-α/IFN-γ处理的HaCaT细胞中，信号通路的磷酸化，包括MAPK,NF-κB,STAT,AKT/PKB，增加，但被异磷普乙素减少。在PMA/离子霉素处理的RBL-2H3细胞中，包括PKC在内的信号通路的激活，MAPK,和AP-1增加，但被异核黄素减少。总之,在TNF-α/IFN-γ处理的HaCaT细胞和PMA/离子霉素处理的RBL-2H3细胞中,异黄体酮通过调节上游转录因子来减少炎症介质的产生。因此,我们认为，异磷内酯具有潜在的治疗效果，特别是在皮肤炎性疾病如AD，通过靶向角质形成细胞和嗜碱性粒细胞。
