Aged Garlic Extract and Its Constituents Inhibit Platelet Aggregation through Multiple Mechanisms1–3

Abstract

Aged garlic extract (AGE) is a complex mixture. Its constituents include allin, cycloalliin, S-allyl-L-cysteine, S-methyl-L-cysteine, S-ethylcysteine, S-1-proponyl-L-cysteine, S-allylmercapto-L-cysteine, fructosyl-arginine, and beta-chlorogenin. It also contains L-arginine, L-cysteine, and L-methionine. AGE reduces the parameters associated with cardiovascular disease, including the inhibition of platelet aggregation. However, the underlying mechanisms have yet to be established and are the subject of this study. AGE inhibited platelet aggregation in a concentration-dependent manner, and this achieved significance between concentrations of 1.56-25% (v:v). The constituents of AGE, when tested as a mixture, displayed a biphasic pattern of inhibition, although this was not significant. L-Methionine displayed anti-aggregatory properties at concentrations of 0.00078, 0.00625, and 0.1 mmol/L, whereas L-arginine and L-cysteine were effective at 9 mmol/L. However, when the constituents and the amino acids were tested together, significant inhibition of platelet aggregation was observed only at a concentration of 1 mmol/L. AGE also displayed disaggregatory properties at concentrations of 12.5 and 25% (v:v). The constituents and the amino acids, when tested as a mixture, displayed disaggregatory properties at concentrations of 0.25 and 1 mmol/L. In contrast, a diethyl-ether extract of AGE had no effect on platelet aggregation. When platelets were stimulated with either A23187 or ADP, an increase in intraplatelet Ca2+ accompanied platelet aggregation. This increase in Ca2+ was abolished in the presence of AGE. It is likely that AGE works in a synergistic manner and exerts multiple effects on the biochemical pathways involved in platelet aggregation.