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Review
. 2023 Mar 28;12(4):660.
doi: 10.3390/antibiotics12040660.

Regulation of Host Defense Peptide Synthesis by Polyphenols

Isabel Tobin  1 , Guolong Zhang  1
Affiliations
Review

Regulation of Host Defense Peptide Synthesis by Polyphenols

Isabel Tobin et al. Antibiotics (Basel). .

Abstract

The rise of antimicrobial resistance has created an urgent need for antibiotic-alternative strategies for disease control and prevention. Host defense peptides (HDPs), which have both antimicrobial and immunomodulatory properties, are an important component of the innate immune system. A host-directed approach to stimulate the synthesis of endogenous HDPs has emerged as a promising solution to treat infections with a minimum risk for developing antimicrobial resistance. Among a diverse group of compounds that have been identified as inducers of HDP synthesis are polyphenols, which are naturally occurring secondary metabolites of plants characterized by the presence of multiple phenol units. In addition to their well-known antioxidant and anti-inflammatory activities, a variety of polyphenols have been shown to stimulate HDP synthesis across animal species. This review summarizes both the in vitro and in vivo evidence of polyphenols regulating HDP synthesis. The mechanisms by which polyphenols induce HDP gene expression are also discussed. Natural polyphenols warrant further investigation as potential antibiotic alternatives for the control and prevention of infectious diseases.

Keywords: antibiotic alternatives; antimicrobial resistance; host defense peptides; polyphenols.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Antimicrobial and immunomodulatory activities of host defense peptides (HDPs). HDPs possess direct antimicrobial activity against bacteria, fungi, viruses, and parasites mainly through membrane disruption. A few HDPs also inhibit bacteria by forming nanonets or targeting bacterial DNA, RNA, proteins, or lipid II of the cell wall. Immunomodulatory effects of HDPs mainly include recruitment and activation of immune cells and regulation of inflammatory response.
Figure 2
Figure 2
Classifications and health benefits of polyphenols. One representative compound is shown in each category for illustrative purposes.
Figure 3
Figure 3
Molecular mechanisms of polyphenol-mediated induction of host defense peptide (HDP) genes. Certain polyphenols are shown to activate the MAPK pathway to upregulate the expression of human β-defensin (DEFB) genes (A). Resveratrol and genistein enhance sphingosine-1-phopshate (S1P) synthesis and NF-κB activation to induce cathelicidin antimicrobial peptide (CAMP) gene expression (B). Several polyphenols inhibit KEAP1 to allow nuclear translocation of NRF2 to induce the expression of hepcidin antimicrobial peptide (HAMP) (C). Many polyphenols function as inhibitors of histone deacetylase (HDAC), DNA methyltransferase (DNMT), or histone methyltransferase (HMT) to increase histone acetylation while reducing DNA and histone methylation to promote a relaxed chromatin structure in favor of HDP transcription (D). A few polyphenols directly enhance the histone acetyltransferase (HAT) activity to promote HDP transcription (D). HDP gene expression may be enhanced by polyphenols through modulating the synthesis of metabolites, such as butyrate, by the intestinal microbiota (E).
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