Abstract
Morus alba L. (MAL) extract has been used in traditional medicine for its cardioprotective and antiplatelet effects, while another herbal remedy, Schisandra chinensis (SCC), has been reported to have anti-inflammatory and antioxidant properties. We evaluated underlying cellular changes exerted by extracts of these plants on platelet function and effects of SCC + MAL on in vivo thrombus formation using AV shunt and tail thrombosis-length models in rats. In vitro platelet aggregation, granule secretion, and [Ca2+]i release assays were carried out. The activation of integrin αIIbβ3 and phosphorylation of downstream signaling molecules, including MAPK and Akt, were investigated using cytometry and immunoblotting, respectively. Scanning electron microscopy (SEM) was used to evaluate changes in platelet shape and HPLC analysis was carried out to identify the marker compounds in SCC + MAL mixture. In vivo thrombus weight and average length of tail thrombosis were significantly decreased by SCC + MAL. In vitro platelet aggregation, granule secretion, [Ca2+]i release, and integrin αIIbβ3 activation were notably inhibited. SCC + MAL markedly reduced the phosphorylation of MAPK pathway factors along with Akt. HPLC analysis identified four marker compounds: isoquercitrin, astragalin, schizandrol A, and gomisin A. The extracts exerted remarkable synergistic effects as natural antithrombotic and antiplatelet agent and a potent drug candidate for treating cardiovascular diseases.
Highlights
Platelet activation underlies thrombotic cardiovascular diseases (CVD) and events such as coronary artery disease (CAD), atherosclerosis, myocardial infarction, and thrombosis which are responsible for increased morbidity and mortality, and their prevalence in western world is increasing at a high pace [1]
Circulation disturbances at locations of atherosclerotic plaque rupture stimulate platelet activation and arterial thrombus formation [30]. We evaluated both extracts in vivo against thrombus formation and found Schisandra chinensis (SCC) + Morus alba L. (MAL) to be a potent combination compared with SCC or MAL alone; the mixture may be a natural antithrombotic agent with potential to prevent thrombosis or CVD
Our study demonstrates the inhibitory potential of SCC + MAL on collagen-stimulated platelet aggregation, which is indicated by a clear suppression of [Ca2+]i mobilization, Cell count Fibrinogen binding (%)
Summary
Platelet activation underlies thrombotic cardiovascular diseases (CVD) and events such as coronary artery disease (CAD), atherosclerosis, myocardial infarction, and thrombosis which are responsible for increased morbidity and mortality, and their prevalence in western world is increasing at a high pace [1]. Platelet activation plays a critical role in hemostasis, but inappropriate activation can lead to development of serious cardiovascular disorders, and is the causal factor in atherosclerosis [2, 3]. Therapeutic antiplatelet agents have been shown to reduce the incidence of CVD [5]. One of the approaches may include use of natural products, such as plant extracts as antithrombotic agents and anticoagulants [7]. The development of these diseases may be slowed down through the use of dietary supplements and natural products [8]. Some dietary and herbal compounds have been shown to decrease the risks associated with CVD [9]
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