Liu C, Zhu L, Fukuda K, Ouyang S, Chen X, Wang C, Zhang C, Martin B, Gu C, Qin L, Rachakonda S, Aronica M, Qin J, Li X
Science Signaling
2017 vol: 10, issue 467 (February)
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.
Topics: Measure binding affinity, Monolith – Microscale Thermophoresis, Organic solvents, Proteins, Publications, Small molecules, Supplements
