Ulmus parvifolia Modulates Platelet Functions and Inhibits Thrombus Formation by Regulating Integrin αIIbβ3 and cAMP Signaling

Abstract

Background: The prevalence of cardiovascular diseases (CVDs) is increasing at a high rate, and the available treatment options, sometimes, have complications which necessitates the need to develop safer and efficacious approaches. Ethnomedicinal applications reportedly reduce CVD risk. Ulmus parvifolia Jacq. (Ulmaceae) commonly known as Chinese Elm or Lacebark Elm, is native to China, Japan, and Korea. It exhibits anti-inflammatory, antiviral, and anticancer properties, but its anti-platelet properties have not yet been elucidated. Purpose: To investigate the pharmacological anti-platelet and anti-thrombotic effects of U. parvifolia bark extract. Study Design and Methods: Human and rat washed platelets were prepared; light transmission aggregometry and scanning electron microscopy was performed to assess platelet aggregation and the change in platelet shape, respectively. Intracellular calcium mobilization, ATP release, and thromboxane-B2 production were also measured. Integrin a IIb b 3 activation was analyzed in terms of fibrinogen binding, fibronectin adhesion, and clot retraction. The expression of MAPK, Src, and PI3K/Akt pathway proteins was examined. Cyclic nucleotide signaling pathway was evaluated via cAMP elevation and VASP phosphorylation. Anti-thrombotic activity of the extract was evaluated in vivo using an arteriovenous shunt rat model, whereas its effect on hemostasis in mice was assessed via bleeding time assay. Results: U. parvifolia extract significantly inhibited human and rat platelet aggregation in a dose-dependent manner along with inhibition of calcium mobilization, dense granule secretion, and TxB2 production. Integrin a IIb b 3 mediated inside-out and outside-in signaling events, as evidenced by the inhibition of fibrinogen binding, fibronectin adhesion, and clot retraction. The extract significantly reduced phosphorylation of Src,

Ulmus parvifolia Jacq. Exhibits Antiobesity Properties and Potentially Induces Browning of White Adipose Tissue

“…Peak 1 was identified as +(-) catechin as compared to its standard shown in Figure 1(b) , and peak 2 was identified as catechin-7-O- β -D-apiofuranoside as compared to its standard, as shown in Figure 1(c) . The concentration of catechin detected is 6.14 mg/g, whereas that of catechin-7-O- β -D-apiofuranoside was 156.3 mg/g, as previously described [ 14 ]. GCMS analysis revealed that the main components are hexadecanoic acid and β -sitosterol ( Table 2 ).…”

“…Gut anti-inflammatory agents were also used to regulate obesity-related insulin resistance [ 13 ], which suggests that UP may also be used to treat obesity as UP was traditionally used to treat intestinal inflammation. We have also reported that UP exhibits antiplatelet and antithrombotic activity [ 14 ]. Existing traditional and modern evidence and reports suggest that UP may exhibit antiobesity properties.…”

Antiplatelet and Antithrombotic Effects of Epimedium koreanum Nakai

“…The extent of platelet aggregation was assessed by following the standard procedure of light transmission aggregometry using a Chrono-log aggregometer (Havertown, PA, USA), as previously described [ 17 ]. Briefly, the washed platelets (3 × 10 8 cells/mL) were pre-incubated with vehicle (DMSO, maintained at <0.1%) or different concentrations of EAF for 1 min in the presence of 1 mM calcium chloride (CaCl 2 ), followed by stimulation with various agonists (collagen, ADP, or thrombin) for 5 min with continuous stirring at 37°C.…”

“…A field emission SEM was used to assess platelet shape change and aggregation by obtaining ultrastructure images as previously described [ 17 , 18 ].…”

“…The anti-thrombotic activity of the E. koreanum fraction was assessed in a rat extracorporeal shunt model as previously described [ 9 , 17 ]. Briefly, rats were orally administered with the saline (control), EAF (100–300 mg/kg), or ASA (50 mg/kg) once daily for 3 days.…”