Drug-herb interactions: unexpected suppression of free Danshen concentrations by salicylate

The general population of the U.S. uses over-the-counter herbal medicines. Danshen is a Chinese herbal product used for the treatment of cardiovascular disease. In a previous study we showed that Danshen has significant digoxin-like immunoreactivity, and we used this parameter to monitor total and free Danshen activities in sera (10). In this report we demonstrated strong protein binding of Danshen (50-70%), and we also identified albumin as the major serum protein that binds Danshen. Because salicylate, which is also strongly bound to albumin, is a widely used over-the-counter medicine in the U.S., we studied Danshen-salicylate interaction in vitro. We observed no significant change in free Danshen concentrations as measured by free-digoxin-like activity when salicylate concentrations were subtherapeutic (< or = 100 microg/mL). With therapeutic concentrations of salicylate (> or = 150 microg/mL), the free Danshen concentrations significantly decreased from the control. On the other hand, Danshen can displace salicylate from protein binding, thereby increasing the free salicylate concentration. We conclude that salicylate in therapeutic concentration can significantly decrease free Danshen concentrations, and Danshen can displace salicylate.