Regular ArticleAntiplatelet and antithrombotic activities of salvianolic acid A
Introduction
It is widely accepted that thrombus formation affects the progression of various cardiovascular or cerebrovascular disorders, including unstable angina, myocardial infarction, transient ischemic attack, and atherosclerosis [1]. Platelets play an important role in thrombus formation at the site of damaged blood vessels [2], [3], especially arterial and microvascular thrombi, which are major causes of cardiovascular and cerebrovascular diseases [1], [4]. Collaborative meta-analysis of randomized trials has shown that antiplatelet therapy prevents serious vascular events, arterial occlusion, and venous thromboembolism among a wide range of patients at high risk for occlusive vascular event [5]. Therefore, agents with antiplatelet and antithrombotic effects could have wide therapeutic potential for circulatory diseases [6], [7].
Danshen is the dried root of Salvia miltiorrhizae (Labiatae) and is one of the most versatile Chinese herbal drugs. It has been used clinically to treat and prevent cardiovascular disease, hyperlipidemia, and cerebrovascular disease throughout the world [8], [9], [10]. Salvianolic acid A (SAA, the chemical structure is presented in Fig. 1.) is one of major water-soluble phenolic acids extracted from Danshen. Among seven water-soluble compounds, SAA has shown the most potent protective action against peroxidative damage to biomembranes [11]. Pharmacological tests have revealed that SAA possesses a variety of pharmacological activities. It was found to protect against focal cerebral ischemia and inhibit platelet aggregation by collagen-induced. The effects were better than other water-soluble compounds [12], [13].
However, the natural extracted SAA is low in content, which limits its clinical application. Therefore, synthesis of SAA through chemical conversion of raw material salvianolic acid B (SAB) has been developed by Target Drug Research Co. Ltd. This method could be scaled up for large-scale industrial production. The objective of the present study was to assess the effect of newly synthesized SAA on platelet aggregation, thrombus formation, and blood circulation and to provide pharmacological evidence for clinical applications. In addition, potential underlying mechanisms were also investigated.
Section snippets
Reagents and animals
SAA was provided by Target Drug Research Co. Ltd (Shandong, China). L-lysine aspirin was produced by Anhui Fengyuan Pharmaceutical Co. Ltd (Anhui, China). Heparin sodium injection was purchased from Jiangsu Wanbang Biochemical Medicine Co. Ltd. (Jiangsu, China). Adrenaline hydrochloride was purchased from Tianjin Jinyao amino acids Co. Ltd. (Tianjin, China). Adenosine diphosphate (ADP) was purchased from Shanghai Lanji Biotechnology Co. Ltd. (Shanghai, China). The thromboxane B2 (TXB2) and
Effect on washed rat and human platelet aggregation in vitro
SAA exerted inhibitory effects on ADP, thrombin, and AA-induced platelet aggregation. As shown in Fig. 2, SAA effectively inhibited ADP-induced (10 µM) rat platelet aggregation with IC50 of 390 µg/ml and inhibited thrombin-induced (0.7 U/ml) platelet aggregation with IC50 of 912 µg/ml. In contrast, SAA exerted only mild inhibitory effects (39%) on AA-induced (0.5 mM) platelet aggregation, even at the high concentration of 1000 µg/ml. In addition, ASA (72 µg/ml) and IBMX (76 µg/ml) also considerably
Discussion
In the present study, we examined the antiplatelet and antithrombotic effects of newly synthesized SAA and the pharmacological mechanisms by which it improves blood microcirculation by evaluating its hemorheologic, coagulation, and antiplatelet aggregative activity both in vivo and in vitro. The findings from our study enable the better understanding of SAA, which could ultimately lead to the development of novel pharmaceutical strategies for the treatment of thrombosis diseases.
Our results
Conflict of interest statement
The authors state that they have no conflict of interest.
Acknowledgements
This study was supported by the Programs for Science and Technology Development and Plan of Yantai (No. 2009167).
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