Abstract
Thrombosis is a key pathological event in cardiovascular diseases, and is also the most important targeting process for their clinical management. New drug development in thrombosis treatment is still in great demand. According to the traditional Chinese medicine (TCM) theory, thrombosis belongs to the syndrome of blood stasis. Salvia miltiorrhiza Bunge and Ligusticum striatum DC. are two common TCM herbs with long-term documented function in promoting blood circulation and inhibiting thrombosis, especially when used together. Guanxinning Tablet, a modern Chinese drug which contains extracts of the two herbs, also showed strong therapeutic effects in coronary heart disease. However, the pharmacological mechanism is still lacking for the compatibility of the two herbs. Here, through zebrafish-based in vivo fluorescence screening, we demonstrated the synergistic effects between S. miltiorrhiza Bunge and L. striatum DC. in regulating endogenous thrombosis. Moreover, combined with high-resolution mass spectrometry, the main compounds of the botanical drugs were analyzed and screened in our model system. Interestingly, cryptotanshinone and senkyunolide I, two representative compounds, respectively derived from the two herbs, also showed synergistic antithrombotic effects. Further analysis suggested that they may regulate thrombi formation at different levels via multiple signaling pathways, including oxidative stress, platelet activation and coagulation cascade. Taken together, our findings provided solid biological supports toward the drug compatibility theory of TCM, and suggested cryptotanshinone and senkyunolide I as promising drug candidates in thrombosis management.
Highlights
Thrombosis is the key pathological process in coronary artery disease (CAD), which remains the leading cause of global DALYs for 30 years
In order to inquire whether platelets participate in PHZ-induced haemostasis, the effect of Guanxinning Tablet (GXNT) was tested in the plateletlabelled Tg (CD41:eGFP) transgenic line
Different from Western pharmacological concept, which usually aimed at one compound with one or more identified specific targets, Traditional Chinese medicine (TCM) was formulated through a “polypharmacologic” approach (Newman, 2020)
Summary
Thrombosis is the key pathological process in coronary artery disease (CAD), which remains the leading cause of global DALYs for 30 years. Venous thromboembolism (VET) is a common type of cardiovascular disease, which usually develops in patients with major trauma. Multiple epidemiological studies reported increased incidence of VET in patients with a history of arterial cardiovascular events or with family history of myocardial infraction (Braekkan et al, 2008; Sørensen et al, 2009). Whether arterial and venous thrombosis are linked processes is still controversial, the comorbidity of VET in coronary artery diseases makes the treatment even more challenging. As plaque rupture-initiated platelet activation is usually regarded as the first step in an acute coronary event, antiplatelet therapies are mainly used in the clinical management of CAD. Conjunctive therapeutic approaches, including antiplatelet agents, antiinflammation therapies, immunoregulators, and anticoagulant drugs, may bring more benefits for CAD patients
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