Wild Blueberry (Vaccinium angustifolium Ait.) Polyphenols Target Fusobacterium nucleatum and the Host Inflammatory Response: Potential Innovative Molecules for Treating Periodontal Diseases

J Agric Food Chem. 2015 Aug 12;63(31):6999-7008. doi: 10.1021/acs.jafc.5b01525. Epub 2015 Aug 4.

Abstract

Blueberries contain significant amounts of flavonoids to which a number of beneficial health effects in humans have been associated. The present study investigated the effect of a polyphenol-rich lowbush blueberry (Vaccinium angustifolium Ait.) extract on the two main etiologic components of periodontitis, a multifactorial disorder affecting the supporting structures of the teeth. Phenolic acids, flavonoids (flavonols, anthocyanins, flavan-3-ols), and procyanidins made up 16.6, 12.9, and 2.7% of the blueberry extract, respectively. The blueberry extract showed antibacterial activity (MIC = 1 mg/mL) against the periodontopathogenic bacterium Fusobacterium nucleatum. This property may result from the ability of blueberry polyphenols to chelate iron. Moreover, the blueberry extract at 62.5 μg/mL inhibited F. nucleatum biofilm formation by 87.5 ± 2.3%. Subsequently, the ability of the blueberry extract to inhibit the NF-κB signaling pathway in U937-3xκB cells was investigated. The blueberry extract dose-dependently inhibited the activation of NF-κB induced by F. nucleatum. In addition, a pretreatment of macrophages with the blueberry extract (62.5 μg/mL) inhibited the secretion of IL-1β, TNF-α, and IL-6 by 87.3 ± 1.3, 80.7 ± 5.6, and 28.2 ± 9.3%, respectively, following a stimulation with F. nucleatum. Similarly, the secretion of MMP-8 and MMP-9 was also dose-dependently inhibited. This dual antibacterial and anti-inflammatory action of lowbush blueberry polyphenols suggests that they may be promising candidates for novel therapeutic agents.

Keywords: biofilm; blueberry; cytokine; matrix metalloproteinase; periodontal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Inflammatory Agents / pharmacology*
  • Blueberry Plants / chemistry*
  • Fusobacterium nucleatum / drug effects*
  • Fusobacterium nucleatum / growth & development
  • Humans
  • Macrophages / drug effects
  • Macrophages / immunology
  • Periodontal Diseases / immunology
  • Periodontal Diseases / microbiology*
  • Plant Extracts / pharmacology*
  • Polyphenols / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Plant Extracts
  • Polyphenols