Epigenetic active phytoceuticals activate immune relevant miRNAs important in virus response systems

Background: Viruses significantly affect global health. The few available viricidal and antiviral therapies are expensive and often associated with unwanted side effects. Functional foods as plant extracts (nutraceuticals) are epigenetically active, and multi-target antiviral compounds that affect several steps of the viral life cycle and host proteins. MicroRNAs (miRNAs) post-transcriptionally regulate host and viral gene expression and are responsible for the fine-tuning of gene expression by controlling the expression of their target messenger RNAs (mRNA) in host cells and viruses. Several plant ingredients have been proven to be active against RNA virus infections. Obviously, miRNAs play a central role in the regulation of gene transcription in viral replication and host immune defense. A healthy diet and nutraceuticals can support the fine-tuning of miRNAs. Objectives: The aim of this study was to analyze the effects of epigenetic active phytoceuticals and/or functional foods on immune relevant miRNAs and mRNAs in a healthy human study population. Methods: In a 2-month human intervention study (n=80), a mix of plant extracts (sage extract, green tea extract, berberine, apple extract, onion extract, elderberry extract, and grape skin extract) with proven activity against RNA viruses were examined for the change of miRNA and mRNA patterns involved in virus response systems. Lifestyle and nutritional behavior, including self-reported stress levels, as well as infection frequency as potential cofounders have been raised.  Results: The intervention with secondary plant extracts could modulate the expression of miRNAs involved in the virus defense (miR-30e, miR-877, miR-150) and the expression of NF-κB. The intervention also increased miRNA expression patterns associated with a positive lifestyle. The intervention adapted miRNAs that correlate with an increased risk of infection, smoking, stress, and processed meat products.Conclusion: Plant extracts can enhance the beneficial effects of a healthy nutrition and lifestyle by modulating miRNAs. MiRNAs are promising drug targets for maintaining immune homeostasis.Keywords: antiviral, epigenetic active nutraceutical, miRNA, secondary plant extracts, virus response, plant ingredients, functional foods