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.