Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

ETHNOPHARMACOLOGICAL RELEVANCE: Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified.

MATERIALS AND

METHODS

To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect.

RESULTS

KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect.

CONCLUSIONS

These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases.