Regulation of Host Defense Peptide Synthesis by Polyphenols

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.

The Rationale for Sulforaphane Favourably Influencing Gut Homeostasis and Gut–Organ Dysfunction: A Clinician’s Hypothesis

“…More specific gut and immune-related effects include the inhibition of bacterial urease in the control of Helicobacter pylori infection [60], induction of endogenous antimicrobials such as beta-defensin by the Paneth cells [61], inhibition of LPS-endotoxin binding to Tolllike receptor 4 (TLR4) [62] and inhibition of Substance P to limit mast cell histamine [63,64]. In addition, SFN has been shown to potently downregulate, via Nf-kB, the inflammatory cytokines IL-6 and C-reactive protein (CRP) in overweight, otherwise healthy adults, with these effects being sustained over an extended period [65].…”

Polyphenols as Antioxidant/Pro-Oxidant Compounds and Donors of Reducing Species: Relationship with Human Antioxidant Metabolism

“…Stilbenes, phenolic acids, anthocyanins, flavanols, and isoflavones are all examples of polyphenols with anti-infective potential, as they can induce and/or modulate the synthesis of host defense peptides (HDPs) in various animal species. However, further research is Processes 2023, 11, 2771 2 of 23 needed to fully understand the complex interactions between polyphenols and HDPs [6]. Some of the properties of polyphenols are summarized in Figure 1.…”