In Vitro Antiplatelet Activity of Mulberroside C through the Up-Regulation of Cyclic Nucleotide Signaling Pathways and Down-Regulation of Phosphoproteins.

Hyuk-Woo Kwon,Jung-Hae Shin,Dong-Ha Lee,Man Hee Rhee

doi:10.3390/genes12071024

Abstract

Physiological agonists trigger signaling cascades, called “inside-out signaling”, and activated platelets facilitate adhesion, shape change, granule release, and structural change of glycoprotein IIb/IIIa (αIIb/β3). Activated αIIb/β3 interacts with fibrinogen and begins second signaling cascades called “outside-in signaling”. These two signaling pathways can lead to hemostasis or thrombosis. Thrombosis can occur in arterial and venous blood vessels and is a major medical problem. Platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, controlling platelet activity is important for platelet-mediated thrombosis and cardiovascular diseases. In this study, focus on Morus Alba Linn, a popular medicinal plant, to inhibit the function of platelets and found the containing component mulberroside C. We examine the effect of mulberroside C on the regulation of phosphoproteins, platelet-activating factors, and binding molecules. Agonist-induced human platelet aggregation is dose-dependently inhibited by mulberroside C without cytotoxicity, and it decreased Ca2+ mobilization and p-selectin expression through the upregulation of inositol 1, 4, 5-triphosphate receptor I (Ser1756), and downregulation of extracellular signal-regulated kinase (ERK). In addition, mulberroside C inhibited thromboxane A2 production, fibrinogen binding, and clot retraction. Our results show antiplatelet effects and antithrombus formation of mulberroside C in human platelets. Thus, we confirm that mulberroside C could be a potential phytochemical for the prevention of thrombosis-mediated CVDs.

Highlights

Many studies have been conducted on health and longevity, and new agents that are beneficial for human health can be challenging to identify
Platelets play a fundamental role in thrombosis, and the available antiplatelet drugs effectively reduce thrombosis in patients with cardiovascular disease (CVD)
We examined whether mulberroside C inhibits platelet aggregation and thrombus formation through the concentration of cyclic nucleotides and associated signaling molecules

Summary

Introduction

Many studies have been conducted on health and longevity, and new agents that are beneficial for human health can be challenging to identify. Medicinal plants are major constituents of alternative medicines that lead to new drugs [1]. Cardiovascular diseases (CVDs), in particular, affect human health. Various factors have been identified as causative of cardiovascular disease; the role of platelets is putatively very important. Platelets play a fundamental role in thrombosis, and the available antiplatelet drugs effectively reduce thrombosis in patients with CVDs. some side effects of these drugs have been reported [2]. To develop new antiplatelet drugs, we focused on the antiplatelet activity of various medicinal plants

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Conclusion