Design and synthesis of piperine-based photoaffinity probes for revealing potential targets of piperine in neurological disease

Piperine (PIP) has attracted extensive attention due to its diverse biological activities. In this study, we developed two photoaffinity probes PIP-1 and PIP-2, which are biologically safe and retain PIP's bioactivity, to investigate its protein targets <i>in vivo</i>. Using <i>in situ</i> labeling and cell imaging, we were able to effectively detect and visualize the drug targets of PIP with our probes. Additionally, a series of protein targets of PIP were fished using PIP-2 through proteome profiling, with further validation suggesting that TGFβ1 might be a potential target involved in PIP's effects on neurological diseases. These findings demonstrate that PIP-2 is a valuable tool for identifying the targets of PIP.