Thrombosis inhibited by Corydalis decumbens through regulating PI3K-Akt pathway

As a chronic multifactorial disease, thrombus is a phenomenon that blood clots or some components stick to each other in the atrial chamber or blood vessel, and the blood status change from liquid to solid mass. Under the normal physiological state, the thrombosis is controlled by the regulatory physiological system. However, thrombosis is initiated when pathological processes overwhelm the hemostatic system or the hemostatic balance shifts to the pro-coagulant side. In hypercoagulable state, excessive thrombus formation can occur, ultimately resulting in occlusion of blood vessels. Thrombus was divided into arterial and venous thrombosis, the former is initiated by vascular endothelial injury, often accompanied by the rupture of atherosclerotic plaques and might lead to serious complications such as ischemic stroke and myocardial infarction, while the latter primarily stems from blood stasis and cause pulmonary embolism and chronic venous thromboembolism (Chen et al., 2022).

Deep venous thrombosis is one of the most common venous thromboembolic diseases with high postoperative recurrence rate and low cure rate. According to data from the World Health Organization, the number of cardiovascular disease deaths is projected to rise from an estimated 18.9 million in 2020 to over 22.2 million in 2030 and 32.3 million in 2050 (WHO, 2018), which will contribute to a significant economic and social burden in the near future. Since many years ago, antithrombotic drugs have been extensively investigated and developed as potential treatments for thrombus formation, categorized into three distinct classes encompassing fibrinolysis, anticoagulation and antiplatelet aggregation (Chen et al., 2015). Among them, the inhibition of platelet aggregation is considered to be a very important approach to prevent the progression of thrombotic diseases (Zhang et al., 2017). Currently, antiplatelet drugs such as aspirin and clopidogrel are commonly used to prevent platelet-related thrombosis diseases (Kim et al., 2016). Heparin is also one of the effective antithrombotic drugs and has attracted a great deal of attention due to its highly anticoagulant capacity. However, these medications have been associated with various side effects. Aspirin was expressed as gastrointestinal reactions (Kedir et al., 2021), while clopidogrel has shown association with bleeding (Pereira et al., 2019). Heparin remains challenged by its risk of bleeding (massive hemorrhage) through intravenous injection and the side effects of its short half-life time in the body (Chen et al., 2016). In comparison, Chinese medicine offers affirmative and continuous treatment effects with minimal side effects. Therefore, the development of antithrombotic drugs from natural Chinese medicinal herbs has become an important focus of research.

Corydalis decumbens (C. decumbens), a traditional botanical medicine and also called “Xiatianwu” in Chinese Pharmacopoeia, riching in isoquinoline alkaloids mainly involving tetrahydropalmatine (TET) and protopine (PRO) (Wu et al., 2013), has been used as a treatment for blood syndrome from ancient times owing to possessing the properties of removing blood stasis and promoting blood circulation (Tan et al., 2022). Meanwhile, previous research reported that C. decumbens extracts had neuroprotective effects on cerebral hemorrhage rats, which might be related to inhibit the thrombus formation and eliminate inflammation (Pan et al., 2020). Additionally, tetrahydropalmatine (TET), the main component of C. decumbens can trigger angiogenesis (Cui et al., 2021) and protect pulmonary vascular endothelial cells from radiation-induced apoptosis through inhibiting the CaSr/PLCγ1 pathway (Yu et al., 2016). Thus, it was conjectured that C. decumbens might have an inhibitory effect on thrombosis. Therefore, this study aims to confirm the effect of C. decumbens against thrombosis and found the active alkaloids TET and PRO using carrageenan-induced tail thrombus mice and H2O2-induced HUVECs, further exploring the preliminary mechanism. This study provided a scientific basis for the future application of C. decumbens in antithrombotic therapy.

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