Abstract

A large body of evidence highlights that propolis exerts many biological functions that can be ascribed to its antioxidant and anti-inflammatory components, including different polyphenol classes. Nevertheless, the molecular mechanisms are yet unknown. The aim of this study is to investigate the mechanisms at the basis of propolis anti-inflammatory and antioxidant activities. The effects of two brown and green propolis extracts—chemically characterized by RP-HPLC-PDA-ESI-MSn—on the expression levels of miRNAs associated with inflammatory responses (miR-19a-3p and miR-203a-3p) and oxidative stress (miR-27a-3p and miR-17-3p), were determined in human keratinocyte HaCat cell lines, treated with non-cytotoxic concentrations. The results showed that brown propolis, whose major polyphenolic components are flavonoids, induced changes in the expression levels of all miRNAs, and was more active than green propolis (whose main polyphenolic components are hydroxycinnamic acid derivatives) which caused changes only in the expression levels of miR-19a-3p and miR-27a-3p. In addition, only brown propolis was able to modify (1) the expression levels of mRNAs, the target of the reported miRNAs, which code for Tumor Necrosis Factor-α (TNF-α), Nuclear Factor, Erythroid 2 Like 2 (NFE2L2) and Glutathione Peroxidase 2 (GPX2), and (2) the protein levels of TNF-α and NFE2L2. In conclusion, brown and green propolis, which showed different metabolite profiles, exert their biological functions through different mechanisms of action.

Highlights

  • Propolis, known as bee glue, is a complex mixture, produced by bees, mainly Apis mellifera L.It contains resin and other materials collected by bees from various botanical sources—plant leaves, buds and exudates—which are digested by bee saliva enzymes and mixed with beeswax.Nutrients 2017, 9, 1090; doi:10.3390/nu9101090 www.mdpi.com/journal/nutrientsAbout 50% of propolis is comprised of plant resin, with beeswax accounting for approximately a further 30%

  • Expression levels dropped for the two lowest concentrations cells expected, we found that messenger RNA (mRNA) expression levels dropped for the two lowest concentrations in cells

  • In a model system mimicking physiological conditions, this investigation has found that brown propolis exerts anti-inflammatory activity through an epigenetic mechanism of action, being able to increase the expression levels of miR-19a-3p and miR-203a-3p, downregulate mRNA coding for Tumor Necrosis Factor-α (TNF-α) and downregulate TNF-α itself—a well-known proinflammatory cytokine involved in the initiation and propagation phases of inflammatory response—by the induction of Nuclear Factor kB

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Summary

Introduction

Known as bee glue, is a complex mixture, produced by bees, mainly Apis mellifera L.It contains resin and other materials (lipophilic material from leaves, mucilage, gum, latex) collected by bees from various botanical sources—plant leaves, buds and exudates—which are digested by bee saliva enzymes and mixed with beeswax.Nutrients 2017, 9, 1090; doi:10.3390/nu9101090 www.mdpi.com/journal/nutrientsAbout 50% of propolis is comprised of plant resin, with beeswax accounting for approximately a further 30%. Known as bee glue, is a complex mixture, produced by bees, mainly Apis mellifera L. It contains resin and other materials (lipophilic material from leaves, mucilage, gum, latex) collected by bees from various botanical sources—plant leaves, buds and exudates—which are digested by bee saliva enzymes and mixed with beeswax. Propolis contains vitamins, including B1, B2, B6, C and E, and amino acids, derived from the bees’ metabolisms [1,2]. With progress being made in analytical methods, more than 300 compounds have been identified in propolis to date, including flavonoids, terpenoids, phenolic acids and phenolic esters and sugars

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