Efficient Discovery of Syk-Targeting Phenolic Acids from Orthosiphon aristatus and Their Antiplatelet Activities

Orthosiphon aristatus is widely used as a popular functional tea in Southeast Asian countries. A TLC/UPLC-TOF-MS/polymeric MDF strategy was designed to guide the isolation of 25 phenolic acids (PAs) from O. aristatus, including 14 new compounds (1-14). Through extensive spectroscopic analysis, the structures of the compounds were elucidated. Additionally, plausible biosynthetic pathways were deduced. The antiplatelet aggregation activities of the PAs were evaluated. Compounds of the salvianolic acid type exhibited broad-spectrum antiplatelet effects, with compound 17 demonstrating the most potent effect in a concentration-dependent manner. Bicyclo[2.2.2]octane-type PAs were highly specific to collagen-induced aggregation, with 22 demonstrating the most potent effect. It has been further confirmed that active bicyclo[2.2.2]octane-type PAs (22 and 23) can directly interact and inhibit Syk and then inhibit the GPVI pathway, which is unique to collagen-induced aggregation. The work laid the foundation for the further development of O. aristatus as a cardiovascular health supplement.