title: Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice.
abstract: Macrophages, owning variable phenotypes and diverse functions, were becoming the target cells in inflammatory, infectious and autoimmune diseases. In the present study, we evaluated the effect of 5,7,3',4',5'-pentamethoxyflavanone (abbreviated as PMFA), a kind of flavonoid, on macrophage polarization, and investigated the underlying mechanism. We found that PMFA significantly inhibited M1 macrophage polarization and diminished the proinflammatory cytokines, meanwhile it greatly enhanced M2 macrophage related molecules. Moreover, PMFA facilitated the phenotype shift from M1 to M2. However, PMFA only slightly inhibited the activation of T and B cells. Further researches showed that the mechanisms can be attributed to PMFA's down-regulation on p-STAT1 and up-regulation on p-STAT6, the pivotal regulatory molecules for M1 and M2 polarization, respectively. In addition, PMFA ameliorated LPS- and cecal ligation and puncture (CLP)-induced sepsis in mice, as assessed by the raise of survival rate, descend of tissue damage and bronchoalveolar lavage fluid (BALF) cytokines. PMFA significantly decreased the expression of IL-1β, IL-6 and TNF-α and reduced the infiltration of M1 macrophages in lung. As expected, adoptive transfer of PMFA-pretreated M1 macrophages significantly increased survival rate of LPS-challenged mice compared with control mice. Taken together, the results indicate that PMFA regulates macrophage polarization via targeting the STAT1/STAT6 signals and its potential use in treatment of inflammatory disease.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Feng
authors.affiliation: The Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Song
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China. Electronic address: xudongwu@nju.edu.cn.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China. Electronic address: molpharm@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005434:Flow Cytometry; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy*
chemical_list: C000588600:5,7,3',4',5'-pentamethoxyflavanone; D044950:Flavanones; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; C494080:Stat1 protein, mouse; C494100:Stat6 protein, mouse
keywords: 5,7,3′,4′,5′-Pentamethoxyflavanone (PMFA); Anti-inflammation; Macrophage polarization; STAT1/STAT6 signals; Sepsis