Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, PR China.
J Ethnopharmacol. 2012 Jun 14;141(3):982-8. doi: 10.1016/j.jep.2012.03.029. Epub 2012 Mar 26.
Panax quinquefolium saponins (PQS), a water-soluble antioxidant extracted from a natural herb, radix panacis quinquefolii (American Ginseng), has yielded encouraging results in the treatment of atherosclerotic diseases. However, the underlying mechanisms remain unclear. Here, we tested the hypothesis that the anti-atherosclerotic effect of PQS might be mediated by suppressing human monocyte-derived dendritic cells (DCs) maturation.
DCs were derived by incubating purified human monocytes with granulocyte macrophage colony stimulating factor (GM-CSF) and IL-4. DCs were pre-incubated with or without PQS and stimulated by oxidized low density lipoprotein (ox-LDL). Expression of DCs membrane molecules (CD40, CD86, CD1a, HLA-DR) and endocytotic ability were analyzed by FACS, cytokines (IL-12 and TNF-α) were measured by ELISA. Nuclear factor (NF)-κB signaling pathway was determined by Western blotting, and RT-PCR. NF-κB activation was quantified by ELISA.
PQS reduced ox-LDL induced immunophenotypic expressions (CD40, CD1a, CD86, and HLA-DR) and cytokine secretions (IL-12 and TNF-α), and improved endocytotic ability of DCs. These above phenomena were accompanied by decreased protein expression and binding activity of nuclear localized c-Rel subunit.
Our study suggested that PQS inhibited ox-LDL induced immune maturation of DCs in vitro, which might be in part mediated by NF-κB signal transduction pathway.
从天然草药西洋参（美国人参）中提取的水溶性抗氧化剂——人参皂苷（PQS），在治疗动脉粥样硬化疾病方面已取得令人鼓舞的效果。然而，其潜在机制尚不清楚。在这里，我们检验了这样一个假设，即 PQS 的抗动脉粥样硬化作用可能是通过抑制人单核细胞衍生的树突状细胞（DCs）成熟来介导的。
通过用粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）孵育纯化的人单核细胞来衍生 DCs。将 DCs 与或不与 PQS 预孵育，然后用氧化低密度脂蛋白（ox-LDL）刺激。通过流式细胞术分析 DCs 膜分子（CD40、CD86、CD1a、HLA-DR）和内吞能力，通过 ELISA 测量细胞因子（IL-12 和 TNF-α）。通过 Western blot 和 RT-PCR 测定核因子（NF）-κB 信号通路。通过 ELISA 定量 NF-κB 激活。
PQS 降低了 ox-LDL 诱导的免疫表型表达（CD40、CD1a、CD86 和 HLA-DR）和细胞因子分泌（IL-12 和 TNF-α），并改善了 DCs 的内吞能力。这些现象伴随着核定位的 c-Rel 亚基的蛋白表达和结合活性降低。
我们的研究表明，PQS 抑制了 ox-LDL 诱导的 DCs 体外免疫成熟，这可能部分是通过 NF-κB 信号转导通路介导的。
