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Molecules. 2017 Jan 22;22(1). pii: E183. doi: 10.3390/molecules22010183.

Phloretin Exerts Anti-Tuberculosis Activity and Suppresses Lung Inflammation.

Author information

1
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea. dasom921012@konkuk.ac.kr.
2
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea. boby8520@konkuk.ac.kr.
3
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea. humnath@konkuk.ac.kr.
4
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea. chk90@konkuk.ac.kr.
5
Korean National Tuberculosis Association, Seoul 06763, Korea. viweon@naver.com.
6
Department of Immunology, School of Medicine, Konkuk University, Seoul 05029, Korea. jungid@kku.ac.kr.
7
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea. ymkim@konkuk.ac.kr.

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.

KEYWORDS:

Mycobacterium tuberculosis; antibiotics; inflammation; natural compound; phloretin

PMID:
28117761
PMCID:
PMC6155841
DOI:
10.3390/molecules22010183
[Indexed for MEDLINE]
Free PMC Article

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