Basic nutritional investigationInhibition of blood platelet adhesion and secretion by different phenolics from Yucca schidigera Roezl. bark
Introduction
Activation of blood platelets by an agonist leads to many events including morphologic change, adhesion, secretion, and aggregation. Platelet adhesion to the damaged vessel wall is the first step in hemostasis and thrombosis and is followed by the spreading and activation of these cells, resulting in the release of their granule content and formation of aggregates. Platelet interaction with the vessel wall is mediated by a series of membrane receptors and by adhesive proteins (collagen, fibrinogen, von Willebrand factor, fibronectin, laminin, and thrombospondin) present in plasma or derived from platelet granules or from the vessel wall. Blood platelet activation is fundamental to a wide range of physiologic and pathologic processes, including thrombosis and heart diseases. Normal hemostasis is initiated when platelets are exposed to the subendothelial matrix, where they adhere to collagen by specific cell-surface receptors. This adhesion step is followed by platelet activation that is accompanied by synthesis and release of various active molecules involved in the hemostasis. Platelet hyperactivity is one of the most important factors responsible for thrombosis and the incidence of cardiovascular diseases. Blood platelets are extremely sensitive and can be affected by the constituents of human diet. Inhibition of platelet functions decreases heart diseases and atherosclerosis. There are many nutritive and non-nutritive compounds present in the diet that may affect platelet function in various ways. Therefore, the compounds that inhibit platelet function are of great interest. In fruits and vegetables, there are many bioactive compounds such as polyphenolic compounds, vitamins, and carotenoids [1], [2], [3], [4], [5], [6]. Among the polyphenolic compounds, resveratrol (3,4′,5-trihydroxystilbene), is of special interest. It is a naturally occurring molecule present in some plants, including Yucca schidigera, and a relatively large amount of resveratrol is found in grapes and red wine [7], [8]. Resveratrol has a very broad range of biological properties, but the mechanisms involved in the action of resveratrol and its derivates are not well known. One of the proposed mechanisms for the cardioprotective effect of resveratrol is the inhibition of low-density lipoprotein oxidation and platelet aggregation [9], [10]. Our preliminary experiments showed that resveratrol has antiplatelet action and distinctly decreases various steps of platelet activation (platelet adhesion, aggregation, and secretion) [11], [12], [13], [14], [15].
This study investigated and compared the action of resveratrol (compound 2 in our study) with other phenolic compounds isolated from the bark of Y. schidigera (trans-3,3′,5,5′-tetrahydroxy-4′-methoxystilbene, compound 1; yuccaol A, compound 3; and yuccaol C, compound 4) on the first step of platelet activation (platelet adhesion to collagen and fibrinogen) in pig blood and on the secretory process in pig platelets stimulated by a strong platelet agonist, thrombin. Pig blood platelets, due to their morphologic and functional similarities to human platelets, are a very good model for preliminary investigations.
Yucca schidigera is a plant that grows widely in Mexico, and it is well known because of its very large content of steroidal saponins. Our previous studies have shown that the concentration of phenolic compounds in this plant species is also extremely high [16]. Because Y. schidigera products have a generally recognized as safe label and are approved by the U.S. Food and Drug Administration to be used as food additives, we deemed this of interest to study and compared the influence of different phenolic compounds from Y. schidigera with their alcohol extracts on platelet adhesion and secretion. Our preliminary results demonstrated that phenolic compounds from Y. schidigera decrease platelet aggregation, eicosanoid synthesis in blood platelets [17], and inhibit the production of reactive oxygen species (ROS) in these cells [18]. The purpose of the present study was to determine the effects of polyphenolic compounds from Y. schidigera on platelet adhesion and secretion.
Section snippets
Plant material
Yucca (Y. schidigera) bark was obtained from Desert King International (Chula Vista, CA, USA).
Chemicals
Thrombin, collagen, bovine serum albumin, and bicinchoninic acid solution were purchased from Sigma (St. Louis, MO, USA). Fibrinogen was prepared from pig blood according to the method of Doolittle et al. [19]. Stock solutions of resveratrol and other phenolics were made in 50% dimethylsulfoxide at the concentration of 5 mg/mL, kept frozen, and used for platelet experiments. All other reagents were of
Results
Our comparative studies demonstrated that four different phenolic compounds and extracts of these compounds from Y. schidigera modulate platelet adhesion to collagen and fibrinogen. First, we observed that adhesion to collagen and to fibrinogen of platelets preincubated with phenolics from Y. schidigera and stimulated by thrombin (0.2 U/mL) was changed (Fig. 1, Fig. 2). Preincubation of platelets with resveratrol and extract had inhibitory effects on adhesion of thrombin-stimulated platelets
Discussion
Many different herbal components in folk medicine are antiplatelet agents that inhibit platelet activation (including the well-known aspirin) and have been used in the management of cardiovascular disorders. Currently there is a growing interest in new compounds in the human diet that combine antioxidative and antiplatelet activities. A new source of these compounds may be Y. schidigera bark, where phenolics (with antiaggregation [17] and antioxidative action [18]) are present at high
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This study was supported by grant 506/810 from the University of Lodz and by grant KBN 6 P06A 012 20 from the Polish Committee for Science.