Proteome Microarray-Guided Global View: Multiple Pharmacological Targets of Icariin

Background: Icariin (ICA) is a major bioactive compound extracted from the traditional Chinese medicinal herb Epimedium, demonstrated a broad spectrum of pharmacological properties. However, a comprehensive and up-to-date study exclusively focusing on ICA direct binding proteins has not yet been conducted. Methods: HuProt™ 20K human proteome microarray, the highest capacity human protein microarray, is suitable for the applications of small molecule targeting proteins. Here, we constructed an atlas of the ICA-binding proteins directly via proteome microarray. Results: We showed that a total of 246 proteins which directly interacted with ICA. Subsequent PPI network analysis organized these proteins into 4 functionally distinct clusters, revealing that ICA interacts with proteins central to fundamental cellular processes, including protein folding chaperone complexes, the ubiquitin-proteasome system, apoptotic and PI3K-Akt signaling pathways, and nucleotide metabolism. Conclusion: This study constructed an atlas of the ICA-binding proteins directly via microarray, which spans protein folding, ubiquitin-proteasome, apoptosis and nucleotide metabolism, providing a theoretical basis for ICA treatment of diseases caused by dysregulation of these core pathways. Keywords: icariin, proteome microarray, pharmacological targets, protein networks, molecular mechanism