Oleanolic acid, a herb extract, acts as a strong and safe enhancer in the collagen-mediated hemostatic cascade in flow

Abstract

Considerable attention has been paid steadily for efficacy and safety of herb extracts with medicinal benefits, recently. Tranexamic acid (TXA) is a well-known hemostatic agent with strong efficacy but potential thrombus risk. Here, we identified oleanolic acid (OA) as a strong enhancer in promoting adhesion, spreading or aggregation of platelets on immobilized collagen, which exceeds TXA among six herb extracts. In addition, the study demonstrated that TXA could facilitate morphological changes of platelets on collagen, accelerate and enhance intracellular calcium bursting with and without mechanical stimulus, which might cause an excessive hemostatic response and lead to thrombus. While OA exerted a comparable effect specifically under low-shear flow regimes, providing a flow-assisted chemical activation that bypasses the need for high-magnitude mechanical tension but ensures localized efficacy. In summary, this study identified OA as a herbal coagulant that showed hemostatic efficacy similar to TXA, but with a better safety profile. It provided a new insight into the flow-assisted mechanism underlying hemostatic efficiency and should be useful in finding novel and safe hemostatic drugs and in developing a practical method for functional identification of hemostatic agents.