Abstract

Botanicals are rich in bioactive compounds, and some offer numerous beneficial effects to animal and human health when consumed. It is well known that phytochemicals in cranberries have anti-oxidative and antimicrobial activities. Recently, an increasing body of evidence has demonstrated that cranberry phytochemicals may have potential benefits that promote healthy aging. Here, we use Caenorhabditis elegans as a model to show that water-soluble cranberry extract standardized to 4.0% proanthocyanidins (WCESP), a major component of cranberries, can enhance host innate immunity to resist against Vibrio cholerae (V. cholerae; wild type C6706 (O1 El Tor biotype)) infection. Supplementation of WCESP did not significantly alter the intestinal colonization of V. cholerae, but upregulated the expression of C. elegans innate immune genes, such as clec-46, clec-71, fmo-2, pqn-5 and C23G10.1. Additionally, WCESP treatment did not affect the growth of V. cholerae and expression of the major bacterial virulence genes, and only slightly reduced bacterial colonization within C. elegans intestine. These findings indicate that the major components of WCESP, including proanthocyanidins (PACs), may play an important role in enhancing the host innate immunity. Moreover, we engaged C. elegans mutants and identified that the p38 MAPK signaling, insulin/IGF-1 signaling (IIS), and HSF-1 play pivotal roles in the WCESP-mediated host immune response. Considering the level of conservation between the innate immune pathways of C. elegans and humans, the results of this study suggest that WCESP may also play an immunity-promoting role in higher order organisms.

Highlights

  • A broad array of evidence demonstrates a positive link between plant phytochemicals and health-promoting effects, such as cancer prevention, bone health, a reduced risk of cardiovascular and metabolic diseases, etc. [1,2,3,4,5,6,7,8,9,10,11,12]

  • We adopted this concentration to examine whether water-soluble cranberry extract standardized to 4.0% PACs (WCESP) supplementation may protect hosts from pathogenic infection by carrying out V. cholerae killing assays in C. elegans

  • Wild-type C. elegans N2 worms were supplemented with WCESP on nematode growth medium (NGM) plates from the early L1 stage until L4/young adult

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Summary

Introduction

A broad array of evidence demonstrates a positive link between plant phytochemicals and health-promoting effects, such as cancer prevention, bone health, a reduced risk of cardiovascular and metabolic diseases, etc. [1,2,3,4,5,6,7,8,9,10,11,12]. American cranberry (Vaccinium macrocarpon) is rich in various polyphenols, including anthocyanins, flavonols, proanthocyanidins (PACs), phenolic acids, stilbenes, etc. Studies in model systems demonstrated that the water-soluble cranberry extract standardized to 4.0% PACs (WCESP) can promote animals’ response to abiotic stress accompanied with a prolonged lifespan [17,18,19,20,21]. In this context, it is of interest to examine whether this WCESP may promote the host response to biotic stressors, such as pathogenic bacteria

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