Abstract
S-allylcysteine (SAC) is a bioactive substance found in aged garlic and is known to improve liver function, inhibit organ fibrosis, and have anticancer activity. A single oral administration of SAC (10 mg/kg) increased tail vein blood flow in rats by up to 10% over one hour, and a 0.3% SAC mixed diet increased tail vein blood flow compared to the normal diet after 2 months. To investigate the relationship between these increases in blood flow and nitric oxide (NO), a single oral dose of SAC (100 mg/kg) followed by a 3-day administration of L-nitroarginine (LNA, 2 mM), an NO synthase inhibitor, resulted in the disappearance of SAC-induced increases in blood flow. Whereas, when LNA and excess L-arginine were mixed with drinking water, the SAC-induced increase in blood flow was restored. This phenomenon was also observed in plantar blood flow. These results indicate that the increase in blood flow induced by SAC is NO-dependent. To investigate the relationship between these increases in blood flow and NO, a single oral dose of SAC (100 mg/kg) followed by a 3-day administration of LNA (2 mM), resulted in the disappearance of SAC-induced increases in blood flow. Whereas, when LNA and excess L-arginine were mixed with drinking water, the SAC-induced increase in blood flow was restored. This phenomenon was also observed in plantar blood flow. These results indicate that the increase in blood flow by SAC is NO-dependent. Next, Western blotting of vasodilator-stimulated phosphoprotein (VASP) was performed to confirm this in a vascular model. Phosphorylated VASP (pVASP) is characterized as a substrate for both cGMP-dependent and cAMP-dependent kinases. LNA abolished the aortic pVASP band, whereas LNA plus SAC partially recovered. Focusing on the NO-independent vasodilator H2S, measurements of plasma reactive persulfide showed that LNA treatment significantly reduced thiols, i.e., cysteine, cystine, glutathione (GSH), and H2S. Of the thiols reduced by LNA treatment, the concurrent SAC application significantly restored the reduction of cysteine and cystine, but not H2S. These results suggest that SAC may maintain nitrosothiols (compounds of nitric oxide and thiols) that act as NO donors and indirectly increase the bioavailability of NO, resulting in blood flow augmentation through its antioxidant capacity by free radical scavenging.
