2. Academic Validation
  3. The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo

The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo

  • Sci Signal. 2017 Feb 21;10(467):eaaf8823. doi: 10.1126/scisignal.aaf8823.
Caini Liu 1,  Liang Zhu 2 3,  Koichi Fukuda 2,  Suidong Ouyang 1,  Xing Chen 1,  Chenhui Wang 1 4,  Cun-Jin Zhang 1 5,  Bradley Martin 1,  Chunfang Gu 1,  Luke Qin 1,  Suguna Rachakonda 6,  Mark Aronica 7,  Jun Qin 8 3,  Xiaoxia Li 9
Affiliations

Affiliations

  • 1 Department of Immunology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
  • 2 Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • 3 Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • 4 Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
  • 5 Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 6 National Institutes of Health Center for Accelerated Innovations, Cleveland Clinic, Cleveland, OH 44195, USA.
  • 7 Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • 8 Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. [email protected] [email protected].
  • 9 Department of Immunology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. [email protected] [email protected].
PMID: 28223414 DOI: 10.1126/scisignal.aaf8823
Abstract

Cyanidin, a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, including asthma, diabetes, atherosclerosis, and Cancer, through its anti-inflammatory effects. We investigated the molecular basis of cyanidin action. Through a structure-based search for small molecules that inhibit signaling by the proinflammatory cytokine interleukin-17A (IL-17A), we found that cyanidin specifically recognizes an IL-17A binding site in the IL-17A receptor subunit (IL-17RA) and inhibits the IL-17A/IL-17RA interaction. Experiments with mice demonstrated that cyanidin inhibited IL-17A-induced skin hyperplasia, attenuated inflammation induced by IL-17-producing T helper 17 (TH17) cells (but not that induced by TH1 or TH2 cells), and alleviated airway hyperreactivity in models of steroid-resistant and severe asthma. Our findings uncover a previously uncharacterized molecular mechanism of action of cyanidin, which may inform its further development into an effective small-molecule drug for the treatment of IL-17A-dependent inflammatory diseases and Cancer.

Figures
Products