15,16-Dihydrotanshinone I, a Major Component from Salvia Miltiorrhiza Bunge(Dansham), Inhibits Rabbit Platelet Aggregation by Suppressing Intracellular Calcium Mobilization

다국어 초록 (Multilingual Abstract)

Radix Salviae miltiorrhiza (RSM, 'Dansham' in Korea, 'Danshen' in Chinese), the root of Salviae miltiorrhiza Bunge (Labiate) has been used as Chinese fork medicine for the treatment of cardiovascular diseases such as angina pectoris, coronary heart disease, myocardial infarction, and hypertension. In the present study, we evaluated the inhibitory effects of 15,16-Dihydrotanshinone I, one of the major ingredients of Salvia miltiorrhiza Bunge, on platelet aggregation, with elucidation of its mechanisms of action. 15,16-Dihydrotanshinone I concentration-dependently inhibited collagen-induced aggregation of rabbit washed platelets with $IC_{50}$ of $8.7{\pm}5.6\;{\mu}M$, the potency being about seven-fold greater than EGCG, an active Green tea catechin component ($IC_{50}:56.6{\pm}48.7\;{\mu}M$). 15,16-Dihydrotanshinone I significantly inhibited the intracellular calcium $([Ca^{2+}]_i)$ mobilization in a concentration-dependent manner. 15,16-dihdydrotanshinone I also significantly suppressed collagen (50 ${\mu}g/mL$)-induced liberation of $[^3H]$Arachidonic acid from $[^3H]$Arachidonic acid-incorporated rabbit platelet. In addition, 15,16-Dihydrotanshinone I at 50 ${\mu}M$ slightly but significantly inhibited collagen-induced production of thromboxane $B_2$. These results indicate that 15,16-Dihydrotanshinone I exert potent anti-platelet activity via suppression of $[Ca^{2+}]_i$ mobilization and arachidonic acid liberation.