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Molecules 2017, 22(1), 183; doi:10.3390/molecules22010183

Phloretin Exerts Anti-Tuberculosis Activity and Suppresses Lung Inflammation

1
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea
2
Korean National Tuberculosis Association, Seoul 06763, Korea
3
Department of Immunology, School of Medicine, Konkuk University, Seoul 05029, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Jean-Marc Sabatier
Received: 20 December 2016 / Revised: 17 January 2017 / Accepted: 18 January 2017 / Published: 22 January 2017
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)
View Full-Text   |   Download PDF [3585 KB, uploaded 22 January 2017]   |  

Abstract

An increase in the prevalence of the drug-resistant Mycobacteria tuberculosis necessitates developing new types of anti-tuberculosis drugs. Here, we found that phloretin, a naturally-occurring flavonoid, has anti-mycobacterial effects on H37Rv, multi-drug-, and extensively drug-resistant clinical isolates, with minimum inhibitory concentrations of 182 and 364 μM, respectively. Since Mycobacteria cause lung inflammation that contributes to tuberculosis pathogenesis, anti-inflammatory effects of phloretin in interferon-γ-stimulated MRC-5 human lung fibroblasts and lipopolysaccharide (LPS)-stimulated dendritic cells were investigated. The release of interleukin (IL)-1β, IL-12, and tumor necrosis factor (TNF)-α was inhibited by phloretin. The mRNA levels of IL-1β, IL-6, IL-12, TNF-α, and matrix metalloproteinase-1, as well as p38 mitogen-activated protein kinase and extracellular signal-regulated kinase phosphorylation, were suppressed. A mouse in vivo study of LPS-stimulated lung inflammation showed that phloretin effectively suppressed the levels of TNF-α, IL-1β, and IL-6 in lung tissue with low cytotoxicity. Phloretin was found to bind M. tuberculosis β-ketoacyl acyl carrier protein synthase III (mtKASIII) with high affinity (7.221 × 107 M−1); a binding model showed hydrogen bonding of A-ring 2′-hydroxy and B-ring 4-hydroxy groups of phloretin with Asn261 and Cys122 of mtKASIII, implying that mtKASIII can be a potential target protein. Therefore, phloretin can be a useful dietary natural product with anti-tuberculosis benefits. View Full-Text
Keywords: phloretin; natural compound; Mycobacterium tuberculosis; antibiotics; inflammation phloretin; natural compound; Mycobacterium tuberculosis; antibiotics; inflammation
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Jeon, D.; Jeong, M.-C.; Jnawali, H.N.; Kwak, C.; Ryoo, S.; Jung, I.D.; Kim, Y. Phloretin Exerts Anti-Tuberculosis Activity and Suppresses Lung Inflammation. Molecules 2017, 22, 183.

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