Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, 89081 Ulm, Germany.
Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, 89081 Ulm, Germany; Department of Pharmacognosy, College of Pharmacy, Cairo University, Cairo, 11562 Egypt.
Phytomedicine. 2020 Mar;68:153181. doi: 10.1016/j.phymed.2020.153181. Epub 2020 Feb 6.
Eleutherococcus senticosus or Siberian ginseng is a medicinal plant containing adaptogenic substances believed to regulate immune responses. Both, the root and stem bark are commonly used in traditional medicines.
The purpose of the present study is to chemically characterize E. senticosus root and bark extracts and to compare their effects on functions of human primary macrophages.
HPLC-DAD-MS analysis was used to characterize chemical constituents of alcoholic extracts from E. senticosus root and bark. The data obtained and available databases were combined for network pharmacology analysis. Involvement of predicted pathways was further functionally confirmed by using monocyte-derived human macrophages and endotoxin-free E. senticosus root and bark extracts.
Chemical analysis showed that the root extract contained more syringin, caffeic acid, and isofraxidin than the bark extract. At variance, bark extract contained more sesamin and oleanolic acid. Coniferyl aldehyde and afzelin were below the limit of quantification in both extracts. Network pharmacology analysis indicated that constituents of E. senticosus might affect the immune cell phenotype and signaling pathways involved in cell metabolism and cytoskeleton regulation. Indeed, both extracts promoted actin polymerization, migration, and phagocytosis of E. coli by macrophages pointing to macrophage polarization towards the M2 phenotype. In addition, treatment with E. senticosus root and bark extracts decreased phosphorylation of Akt on Ser473 and significantly reduced expression of the hemoglobin scavenger receptor CD163 by macrophages. Neither extract affected expression of CD11b, CD80, or CD64 by macrophages. In addition, macrophages treated with the bark extract, but not with the root extract, exhibited activated p38 MAPK and NF-κB and released increased, but still moderate, amounts of proinflammatory TNF-α and IL-6, anti-inflammatory IL-10, and chemotactic CCL1, which all together point to a M2b-like macrophage polarization. Differently, the root extract increased the IL-4-induced expression of anti-inflammatory CD200R. These changes in monocytes are in agreement with an increased M2a macrophage polarization.
The ability of E. senticosus root and bark extracts to promote polarization of human macrophages towards anti-inflammatory M2a and M2b phenotypes, respectively, might underlay the immunoregulatory activities and point to potential wound healing promoting effects of this medicinal plant.
刺五加或西伯利亚人参是一种药用植物，含有被认为能调节免疫反应的适应原物质。其根和茎皮都常用于传统药物。
本研究旨在对刺五加根和茎皮提取物进行化学表征，并比较其对人原代巨噬细胞功能的影响。
采用 HPLC-DAD-MS 分析方法对刺五加根和茎皮醇提物中的化学成分进行了表征。所得数据与现有数据库相结合进行网络药理学分析。进一步利用单核细胞来源的人巨噬细胞和无内毒素的刺五加根和茎皮提取物，对预测途径的参与情况进行了功能验证。
化学分析表明，根提取物中含有更多的丁香苷、咖啡酸和异嗪皮啶，而茎皮提取物中含有更多的芝麻素和齐墩果酸。相反，松柏醛和阿夫西定在两种提取物中均低于定量下限。网络药理学分析表明，刺五加的成分可能影响免疫细胞表型以及参与细胞代谢和细胞骨架调节的信号通路。事实上，两种提取物均促进了巨噬细胞对大肠杆菌的肌动蛋白聚合、迁移和吞噬作用，表明巨噬细胞向 M2 表型极化。此外，用刺五加根和茎皮提取物处理后，巨噬细胞中 Akt 丝氨酸 473 的磷酸化显著降低，且血红蛋白清除受体 CD163 的表达明显减少。两种提取物均不影响巨噬细胞中 CD11b、CD80 或 CD64 的表达。此外，仅用茎皮提取物处理的巨噬细胞表现出激活的 p38 MAPK 和 NF-κB，且释放出更多但仍适度的促炎 TNF-α 和 IL-6、抗炎 IL-10 和趋化因子 CCL1，这都表明向 M2b 样巨噬细胞极化。相反，根提取物增加了 IL-4 诱导的抗炎性 CD200R 的表达。这些单核细胞的变化与 M2a 巨噬细胞极化的增加一致。
刺五加根和茎皮提取物促进人巨噬细胞向抗炎性 M2a 和 M2b 表型的极化能力，可能是这种药用植物具有免疫调节活性的基础，并指向其促进伤口愈合的潜在作用。
