Ahn Sungeun, Siddiqi Muhammad Hanif, Aceituno Veronica Castro, Simu Shakina Yesmin, Zhang Jinglou, Jimenez Perez Zuly Elizabeth, Kim Yu-Jin, Yang Deok-Chun
Department of Oriental Medicinal Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
Ginseng Bank, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 446-701, Republic of Korea.
In Vitro Cell Dev Biol Anim. 2016 Mar;52(3):287-295. doi: 10.1007/s11626-015-9983-y. Epub 2015 Dec 29.
Atopic dermatitis (AD) is a chronic skin disease that affects millions of people worldwide. Keratinocytes and macrophages are two cells types that play a pivotal role in the development of AD. These cells produced different chemokines and cytokines, especially thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), as well as nitric oxide (NO) through inducible nitric oxide synthase (iNOS) and COX2 in response to stimulation by TNF-α/IFN-γ and lipopolysaccharide (LPS) respectively. These mediators are thought to be crucial regulators of the pathogenesis of AD. Although several natural compounds to treat AD have been studied, the effect of Rg5:Rk1 from Panax ginseng (P. ginseng) on AD has not yet been investigated. In this study, we evaluated the inhibitory effect of Rg5:Rk1 on TNF-α/IFN-γ stimulated keratinocytes (HaCaT cells) and LPS-stimulated macrophages (RAW 264.7 cells). Enzyme-linked immunosorbent assay (ELISA) data showed that pretreatment of HaCaT cells with Rg5:Rk1 significantly reduced the TNF-α/IFN-γ-induced increase in TARC/CCL17 expression in a dose-dependent manner. In addition, Rg5:Rk1 decreased LPS-mediated nitric oxide (NO) and reactive oxygen species (ROS) production in RAW 264.7 cells. A considerable reduction in messenger RNA (mRNA) expression of the aforementioned AD mediators was also observed. Pretreatment with Rg5:Rk1 attenuated the TNF-α/IFN-γ-induced phosphorylation of p38 MAPK, STAT1, and NF-κB/IKKβ in HaCaT cells. Together, these findings suggest that ginsenoside Rg5:Rk1 may have a potential anti-AD effect by suppressing NF-κB/p38 MAPK/STAT1 signaling.
特应性皮炎（AD）是一种慢性皮肤病，影响着全球数百万人。角质形成细胞和巨噬细胞是在AD发病过程中起关键作用的两种细胞类型。这些细胞产生不同的趋化因子和细胞因子，特别是胸腺和活化调节趋化因子（TARC/CCL17）和巨噬细胞衍生趋化因子（MDC/CCL22），以及分别通过诱导型一氧化氮合酶（iNOS）和COX2响应TNF-α/IFN-γ和脂多糖（LPS）刺激产生的一氧化氮（NO）。这些介质被认为是AD发病机制的关键调节因子。尽管已经研究了几种治疗AD的天然化合物，但人参（P. ginseng）中的Rg5:Rk1对AD的作用尚未得到研究。在本研究中，我们评估了Rg5:Rk1对TNF-α/IFN-γ刺激的角质形成细胞（HaCaT细胞）和LPS刺激的巨噬细胞（RAW 264.7细胞）的抑制作用。酶联免疫吸附测定（ELISA）数据表明，用Rg5:Rk1预处理HaCaT细胞可显著以剂量依赖性方式降低TNF-α/IFN-γ诱导的TARC/CCL17表达增加。此外，Rg5:Rk1降低了RAW 264.7细胞中LPS介导的一氧化氮（NO）和活性氧（ROS）的产生。还观察到上述AD介质的信使核糖核酸（mRNA）表达显著降低。用Rg5:Rk1预处理可减弱HaCaT细胞中TNF-α/IFN-γ诱导的p38 MAPK、STAT1和NF-κB/IKKβ的磷酸化。总之，这些发现表明人参皂苷Rg5:Rk1可能通过抑制NF-κB/p38 MAPK/STAT1信号传导具有潜在的抗AD作用。
