The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo
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
2017 vol: 10, issue 467 (February)
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