Target protein identification of andrographolide based on isomer approach

The target identification of natural products is one of the most challenging issues in the standardized application of traditional Chinese medicine. It is widely recognized that magnetic nanoparticles (MNPs) could function as a tool that capture the target proteins of active molecule. However, the false positives caused by non-specific adsorption should not be ignored. Here, we reported a functionalized MNPs technique that could enrich the target proteins of andrographolide (AG) based on isomers approach. We designed and characterized MNPs and isomers of AG. The combination of the two could be used as an ideal coupling, which provides a feasible method for the target proteins enrichment of AG. In addition, the target proteins were identified by HPLC-MS/MS. Moreover, bioinformatics analysis and systematic computational dockings were performed to search for the interactions between target proteins and AG. Six inflammation-related proteins, including CD4, IKBKB, PKN1, PKN2, YWHAB and YWHAH were proved to be the anti-inflammatory targets of AG. All of the results indicated this integrated system could benefit target identification of bioactive natural products.