Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp (UA), Antwerp, Belgium.
Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp (UA) and University Hospital Antwerp (UZA), Antwerp, Belgium.
BMC Complement Med Ther. 2021 May 12;21(1):141. doi: 10.1186/s12906-021-03310-5.
Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.
Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes.
Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections.
Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.
紫锥菊酊剂草药制剂如今被广泛用于减轻普通感冒呼吸道感染。
转录组、表观基因组和激酶组谱分析允许对标准化紫锥菊（L.）Moench 提取物在 THP1 单核细胞中的全基因组免疫调节作用进行系统生物学水平的表征。
基因表达和 DNA 甲基化分析表明，Echinaforce® 治疗触发抗病毒先天免疫途径，涉及紧张的 IFN 信号、模式识别受体的激活、趋化性和免疫代谢。此外，基于磷酸肽的激酶组活性谱分析和用 filgotinib 的药理学抑制剂实验证实了 JAK-1 依赖性基因表达变化在先天免疫信号中的关键作用。最后，Echinaforce® 处理在基因间 CpG、长/短散在核 DNA 重复元件（LINE、SINE）或长末端 DNA 重复（LTR）处诱导 DNA 超甲基化。这改变了侧翼内源性逆转录病毒序列（HERV）的转录，内源性逆转录病毒序列参与针对病毒感染的进化保守（epi）基因组保护反应。
总之，我们的结果表明，Echinaforce® 植物化学物质通过 tonic IFN 调节模式识别和趋化因子基因表达以及单核细胞中 HERV 的 DNA 重复超甲基化沉默来增强抗病毒先天免疫。这些结果表明，Echinaforce® 治疗的免疫调节有望减轻普通感冒冠状病毒（CoV）、严重急性呼吸综合征（SARS）-CoV 和新出现的 SARS-CoV-2 等感染发作的症状和持续时间，这些病毒的干扰素（IFN）反应受损严重，先天抗病毒防御能力较弱。
