{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:44:32Z","timestamp":1791726272420,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,1,22]],"date-time":"2017-01-22T00:00:00Z","timestamp":1485043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["MSIP-2016R1A2B2008543"],"award-info":[{"award-number":["MSIP-2016R1A2B2008543"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u03bcM, respectively. Since Mycobacteria cause lung inflammation that contributes to tuberculosis pathogenesis, anti-inflammatory effects of phloretin in interferon-\u03b3-stimulated MRC-5 human lung fibroblasts and lipopolysaccharide (LPS)-stimulated dendritic cells were investigated. The release of interleukin (IL)-1\u03b2, IL-12, and tumor necrosis factor (TNF)-\u03b1 was inhibited by phloretin. The mRNA levels of IL-1\u03b2, IL-6, IL-12, TNF-\u03b1, 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-\u03b1, IL-1\u03b2, and IL-6 in lung tissue with low cytotoxicity. Phloretin was found to bind M. tuberculosis \u03b2-ketoacyl acyl carrier protein synthase III (mtKASIII) with high affinity (7.221 \u00d7 107 M\u22121); a binding model showed hydrogen bonding of A-ring 2\u2032-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.<\/jats:p>","DOI":"10.3390\/molecules22010183","type":"journal-article","created":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T10:40:33Z","timestamp":1485168033000},"page":"183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Phloretin Exerts Anti-Tuberculosis Activity and Suppresses Lung Inflammation"],"prefix":"10.3390","volume":"22","author":[{"given":"Dasom","family":"Jeon","sequence":"first","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Cheol","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hum","family":"Jnawali","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chulhee","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5085-0068","authenticated-orcid":false,"given":"Sungwon","family":"Ryoo","sequence":"additional","affiliation":[{"name":"Korean National Tuberculosis Association, Seoul 06763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangmee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1080\/1040869059096","article-title":"Dietary Polyphenols and the Prevention of Diseases","volume":"45","author":"Scalbert","year":"2005","journal-title":"Crit. 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