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Phloretin Exerts Anti-Tuberculosis Activity and Suppresses Lung Inflammation

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea
Korean National Tuberculosis Association, Seoul 06763, Korea
Department of Immunology, School of Medicine, Konkuk University, Seoul 05029, Korea
Author to whom correspondence should be addressed.
Academic Editor: Jean-Marc Sabatier
Molecules 2017, 22(1), 183;
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)
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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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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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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