Abstract
BackgroundHerbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.MethodsTranscriptome, 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.ResultsGene 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.ConclusionsAltogether, 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.
Highlights
Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections
We evaluated Echinaforce®, a commercially registered herbal medicinal tincture of Echinacea purpurea (L.) Moench (A.Vogel Bioforce, Switzerland) in several European countries including Switzerland, Austria, UK, Spain, Netherland, Denmark, Finland, Sweden, Slovenia, as well as Canada
Genes differentially expressed (DEG) by Echinaforce® treatment were enriched for Ingenuity Pathway Analysis (IPA) canonical pathways related to innate immune responses including interferon signaling, interferon regulatory factor (IRF) activation and the role of pattern recognition receptors, among others (Fig. 1bc and Supplementary Table 2)
Summary
Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. Distinct species of the plant genus Echinacea have traditionally been used in North America against infectious diseases and wounds [1, 2]. A wide variety of Echinacea preparations are used world-wide as complementary herbal remedy to improve the immune response to protect against common cold symptoms and influenza infections. Of all Echinacea species, Echinacea purpurea (purple coneflower) is the most popular variety used in Western countries. Different Echinacea purpurea extracts (different species, plant parts, manufacturing) or derived compounds showed antioxidant, antibacterial, antifungal, antiviral and mosquitocidal activities in cell culture experiments [3], absolute comparisons between studies with different preparations remain difficult [4, 5]. The compounds that contribute to these activities are alkylamides, glycoproteins, polysaccharides and caffeic acid derivates that may act independently or in synergy [1, 3, 7,8,9]
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