Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Abstract

Background: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.Methods: A system biology approach involving genomewide transcriptome, epigenome and kinome activity profiles was applied to characterize the immunomodulatory effects of a standardized Echinacea purpurea extract Echinaforce® in THP1 monocytes.Results: Gene expression and DNA methylation analysis revealed activation of innate immunity related antiviral signaling networks, involving IFN, chemotaxis and immunometabolic pathways. 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.Conclusions: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity by JAK1 responsive gene expression and epigenetic regulation of HERVs in monocytes, which supports its prophylactic use against common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2.

Chemistry and Pharmacology of Alkylamides from Natural Origin

“…A comprehensive review of the antiviral potential of Echinacea sp. is available (Hudson and Vimalanathan 2011) and evidence supporting its antiviral effect through innate immunityboosting by JAK1 responsive gene expression and epigenetic regulation of HERVs in monocytes has recently been reported (Declerck et al 2020).…”

The Effect of Fortificated Mulberry Leaves with Echinacea Purpurea on Silkworm (Bombyx mori L.) Physiology and Production

“…Also, it contains polysaccharides that inhibit cell apoptosis and oxidant stress (Vimalanathan et al, 2017;Hou et al, 2020). Echinacea extract might be able to boost the function of monocytes and natural killer cells, which are essential components of the body's immune system and help fight off infections (Declerck et al, 2021).…”