State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210093, China.
Department of Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), TX 78229, USA.
Biochem Pharmacol. 2014 Jun 15;89(4):503-14. doi: 10.1016/j.bcp.2014.03.016. Epub 2014 Apr 2.
Chrysin (5,7-di-OH-flavone), a widely distributed natural flavonoid, has been well documented for involving in various biological activities, especially in regulation of peroxisome proliferator activated receptor γ (PPARγ) activity as a modest modulator. However, the exact molecular mechanism is still unrevealed. In the current study, for the first time, we discovered that, chrysin not only significantly attenuated inflammation in high-fat feeding mice, but also alleviated high fat diet-induced hepatic, muscular steatosis in obese mice without altering the body weight. Chrysin decreases the infiltration of macrophages into adipose tissue in obese mice. In addition, chrysin was also found to induce an anti-inflammatory M2 phenotype and decreases M1 phenotype, both in peritoneal macrophages of obese mice and cultured macrophages in vitro, and thereby, chrysin changed the M1/M2 status. Our data further showed that chrysin regulated the phenotype of macrophages through enhancing the transcriptional activation of PPARγ and the expression of its target genes. Taken together, we conclude that chrysin may serve as an effective modulator of PPARγ during the pathogenesis of inflammation, thereby our findings shed light on the potential therapeutic feature of chrysin in recovering inflammatory diseases via regulating M1/M2 status.
白杨素（5,7-二羟基黄酮），一种广泛分布的天然类黄酮，其参与多种生物活性的作用已有充分的文献记载，特别是作为适度调节剂调节过氧化物酶体增殖物激活受体γ（PPARγ）的活性。然而，确切的分子机制仍未揭示。在本研究中，我们首次发现，白杨素不仅显著减轻高脂喂养小鼠的炎症，而且减轻肥胖小鼠的高脂饮食诱导的肝、肌肉脂肪变性，而不改变体重。白杨素减少肥胖小鼠脂肪组织中巨噬细胞的浸润。此外，还发现白杨素在体外诱导肥胖小鼠腹腔巨噬细胞和培养的巨噬细胞中产生抗炎 M2 表型，并减少 M1 表型，从而改变 M1/M2 状态。我们的数据进一步表明，白杨素通过增强 PPARγ的转录激活和其靶基因的表达来调节巨噬细胞的表型。总之，我们的结论是，白杨素可能在炎症发病机制中作为 PPARγ的有效调节剂，从而为通过调节 M1/M2 状态恢复炎症性疾病的白杨素的潜在治疗特征提供了依据。
