Anti-thrombosis Effects and Mechanisms by Xueshuantong Capsule Under Different Flow Conditions

Abstract

Xueshuantong capsule (XST) is a patented traditional Chinese medicine used for the prevention and treatment of thrombosis. The molecular mechanism of anti-thrombotic effect of XST was investigated through the cross-talk among the platelets/leukocytes, endothelial cells (ECs), and flow shear stress. The Bioflux 1000 system was used to generate two levels of shear stress conditions: 0.1 and 0.9 Pa. Bioflux Metamorph microscopic imaging system was used to analyze the adhesion cell numbers. Protein expressions were detected by western blotting and flow cytometry. The flow-cytometry results showed that under 0.1 Pa flow, XST decreased ADP induced platelets CD62p surface expression in a concentration-dependent manner. Under 0.9 Pa flow, XST at a concentration of 0.15 g⋅L-1 reduced the platelets activation by 29.5%, and aspirin (ASA) showed no inhibitory effects. XST showed similar efficiency on monocytes adhesion both under 0.1 and 0.9 Pa flow conditions, and the inhibition rate was 30.2 and 28.3%, respectively. Under 0.9 Pa flow, the anti-adhesive effects of XST might be associated with the suppression of VE-cadherin and Cx43 in HUVECs. Blood flow not only acts as a drug transporter, but also exerts its effects to influence the pharmacodynamics of XST. Effects of XST on inhibiting platelets activation and suppressing platelets/leukocytes adhesion to injured ECs are not only concentration-dependent, but also shear stress-dependent. The mechanic forces combined with traditional Chinese medicine may be used as a precise treatment for cardiovascular diseases.

Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway

“…Intravenous repeatedly dosing of 500 mg XST for 15 days, the C max of major ginsenosides is approximately 0.09–0.10 g L −1 ( Pintusophon et al, 2019 ). In our previous study, 0.15 g L −1 of XST showed significant effects on platelets activation and aggregation ( Han et al, 2019 ). In this study, we showed that treatment with XST at 0.15 g L −1 remarkably inhibited shear-induced platelet aggregation and treatment with XST at a high concentration of 0.6 g L −1 resulted in slightly greater inhibition ( Figure 3 ).…”

“…Xueshuantong used in TCM for the prevention and treatment of thrombosis contain high content of PNS. Our recent studies show that XST inhibited platelet activation and adhesion to injured endothelial cells (ECs) in vitro ( Han et al, 2019 ) and also inhibited tail thrombosis formation induced by κ-carrageenan in rats and ameliorated vascular hemodynamic status ( Liu et al, 2020 ). Interestingly, such an inhibitory effect of XST was shear-dependent but the underlying mechanism remained unclear.…”

Network Pharmacology-Based Approach to Comparatively Predict the Active Ingredients and Molecular Targets of Compound Xueshuantong Capsule and Hexuemingmu Tablet in the Treatment of Proliferative Diabetic Retinopathy

“…Regarding circulatory-related effects, CXC is considered to be an effective complementary medicine to treat ischemic vascular diseases, such as cerebral infarction and cardiovascular diseases [ 18 , 19 ]. Lyu's study [ 18 ] showed that CXC combined with conventional treatments had better clinical effects than conventional treatments alone.…”

A rapid and sensitive ultra‐high‐pressure liquid chromatography–tandem mass spectrometry method for the determination of notoginsenoside Ft1 in rat plasma with application to pharmacokinetic study

“…Products derived from P. notoginseng including its extracts have been marketed in Western countries as a dietary supplement of functional foods (Ruan, Leong, Yan, & Wang, 2010). P. notoginseng has been shown to be highly effective in eliminating blood stasis, arresting bleeding, and alleviating pain (Chen et al, 2011; Han et al, 2019; Yang, Song, & Chen, 2016). Dammarane‐type saponins that have been isolated from this herb were responsible for the aforesaid biological activities (Li, Wang, Yang, & Wang, 2015; Liu et al, 2009; Wang, Mcentee, Wicks, Wu, & Yuan, 2006), which can be categorized as 20 ( S ) protopanaxadiol (PPD) type and 20 ( S ) protopanaxatriol type according to their aglycones (Qi et al, 2012; Wang et al, 2006).…”