Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
BMC Genomics. 2010 Nov 1;11:612. doi: 10.1186/1471-2164-11-612.
Several Echinacea species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF) of a stem and leaf (S+L) extract of E. purpurea ([BF/S+L/Ep]) containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs) were analyzed using primary cultures.
Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs). Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (Cdh10, Itga6, Cdh1, Gja1 and Mmp8), or were chemokines (Cxcl2, Cxcl7) or signaling molecules (Nrxn1, Pkce and Acss1). TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. In vitro flow cytometry analysis of chemotaxis-related receptors and in vivo cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups.
Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical application of Echinacea or other candidate medicinal plants.
几种紫锥菊属植物已被用作营养保健品或植物药来“免疫刺激”，但其治疗用途的科学证据仍存在争议。在这项研究中，使用标准化和已发表的程序，从紫锥菊的茎和叶提取物的丁醇部分（BF）中提取了一种植物化合物混合物（BF/S+L/Ep），其中包含严格定义的生物活性植物化合物。使用原代培养物分析了这种植物提取物对小鼠骨髓来源树突状细胞（BMDC）的转录组和蛋白质组影响。
用[BF/S+L/Ep]处理 BMDC 不会显著影响树突状细胞（DC）的表型成熟活性。用[BF/S+L/Ep]处理 4 或 12 小时后差异表达基因的 Affymetrix DNA 微阵列和生物信息学分析表明，大多数响应基因与细胞黏附或运动（Cdh10、Itga6、Cdh1、Gja1 和 Mmp8）有关，或者是趋化因子（Cxcl2、Cxcl7）或信号分子（Nrxn1、Pkce 和 Acss1）。处理后的 DC 中基因表达和相关信号通路的 TRANSPATH 数据库分析预测 JNK、PP2C-α、AKT、ERK1/2 或 MAPKAPK 通路为[BF/S+L/Ep]的潜在靶点。同时，蛋白质组分析表明，[BF/S+L/Ep]处理可调节代谢、细胞骨架或 NF-κB 信号相关蛋白的表达。体外趋化相关受体的流式细胞术分析和体内细胞迁移实验进一步表明，与对照组相比，用[BF/S+L/Ep]处理的 DC 能够更有效地迁移到外周淋巴结和脾脏组织中。
本研究结果表明，[BF/S+L/Ep]调节了小鼠免疫系统中 DC 的迁移能力和相关细胞生理学。此外，这里强调的信号网络和分子可能是紫锥菊或其他候选药用植物营养或临床应用的潜在靶点。
