Inhibition of platelet aggregation by chlorogenic acid via cAMP and cGMP-dependent manner

Abstract

In this study, we investigated the effect of chlorogenic acid, a phenolic acid, on collagen (10 μg/ml)-stimulated platelet aggregation. Chlorogenic acid dose-dependently inhibited collagen-induced platelet aggregation, and suppressed the production of thromboxane A2 (TXA2), an intracellular Ca-agonist as an aggregation-inducing autacoidal molecule, which was associated with the strong inhibition of cyclooxygenase (COX)-1 in platelet microsomes having cytochrome c reductase activity. In addition, chlorogenic acid increased significantly the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular Ca-antagonists as aggregation-inhibiting molecules. These results suggest that chlorogenic acid has antiplatelet activity through the reduction of TXA2 and the increase of cAMP and cGMP levels. Therefore, our data demonstrate that chlorogenic acid is a potent inhibitor of collagen-stimulated platelet aggregation, and may be a crucial tool for a negative regulator during platelet activation in thrombotic diseases.

Cordycepin-Enriched WIB801C from Cordyceps militaris Inhibits Collagen-Induced [Ca2+]iMobilization via cAMP-Dependent Phosphorylation of Inositol 1, 4, 5-Trisphosphate Receptor in Human Platelets

“…CE-WIB801C more increased exclusively cAMP than cGMP on collagen-induced platelet aggregation, which trend is as well as those by phenolic compounds such as epigallocatechin-3-gallate (Ok et al ., 2012), chlorogenic acid (Cho et al ., 2012), and caffeic acid (Lee et al ., 2014) that cAMP-dependently inhibited [Ca 2+ ] i mobilization in collagen-activated platelets. The levels of intracellular cAMP and cGMP are regulated by the balance between cyclic nucleotide-producing enzymes, adenylate/guanylate cyclases, and hydrolyzing enzymes, cAMP/cGMP phosphodiesterases (PDEs).…”

Antiplatelet Effects of Caffeic Acid Due to Ca2＋ MobilizationInhibition Via cAMP-Dependent Inositol-1, 4, 5-Trisphosphate Receptor Phosphorylation

“…This is associated with the activation of A-kinase or G-kinase, since these enzymes block Ca 2＋ mobilization by phosphorylating IP3R to inhibit the generation of the TXA2 substrate, AA 18,40) . CAFA (50 μM) increased the cAMP level more so than the cGMP level in the collagen-induced platelet aggregation, a trend that is also observed with respect to phenolic compounds, such as EGCG 11) and chlorogenic acid 36) . The levels of cAMP and cGMP in platelets are regulated by A B lets) achieved by collagen only (Fig.…”

“…2) was associated with the inhibition of the microsomal COX-1 activity ( Table 1). In a previous study, we reported that chlorogenic acid (50 μM), an analogue of CAFA, inhibits the COX-1 activity in platelets to 69.7% compared with that observed (52.5±2.5 pmoL/ min/protein-mg) in the controls in vitro 36) . In addition, the COX-1 inhibitor aspirin (50 μM) inhibited the COX-1 activity in platelets to 11.3% compared with that observed (1.59 nmoL/min/protein-mg) in the controls in vitro 12) .…”

Inhibitory Effects of Epigallocatechin-3-Gallate on Microsomal Cyclooxygenase-1 Activity in Platelets

“…Thus, a compound that can inhibit TXA 2 production-associated enzymes (COX-1 or TXAS), TXA 2 production or TXA 2 action has a potential application as an anti-thrombotic agent (Clutton et al , 2001). Phytochemicals such as ginseng saponin (Lee et al , 2012), chlorogenic acid (Cho et al , 2012), caffedymine (Park, 2007) and sanguinarine (Jeng et al , 2007) inhibited TXA 2 production in agonists-stimulated platelets, which were involved in inhibition of COX-1 activity. These previous reports are accord with fact that the inhibition of agonists-induced platelet aggregation is supported by inhibition of COX-1 rather than TXAS (Lewis and Watts, 1982; Jang et al , 2002).…”