What is S-Allyl cysteine (SAC)?
S-Allyl cysteine (SAC) is an organic compound that is a natural constituent of garlic,black garlic,and aged garlic. Fermented garlic (black garlic, aged garlic) contains much more S-allyl-L-cysteine (SAC) than fresh garlic.
Based on scientific studies, a minimum of 1 mg S-allyl-L-cysteine (SAC) has been shown to have obvious benefits of improving blood circulation, lower cholesterol, reduce high blood pressure, and help with insomnia and antioxidants benefits. Since SAC is stable and water soluble, it is absorbed more quickly and easily by the body, meanwhile SAC also assists in absorption of the fat soluble allicin.
A considerable number of in vivo and in vitro studies have been performed so far in order to test the antioxidant properties of S-allylcysteine (SAC). In these studies, different antioxidant mechanisms have been reported, such as their ability to (1) scavenge reactive oxygen (ROS) and nitrogen (RNS) species; (2) increase enzymatic and nonenzymatic antioxidants levels; (3) activate Nrf2 factor; or (4) inhibit some prooxidant enzymes (xanthine oxidase, cyclooxygenase, and NADPH oxidase).
Given that S-Allyl cysteine (SAC) is the most abundant compound in fermented garlic (black garlic, aged garlic), the present paper brings special attention to the physicochemical characteristics, toxicity, pharmacokinetics, tissue distribution, and metabolism of this compound, as well as on the different antioxidant mechanisms involved in its protective actions in different experimental models of toxicity.
Substantial evidence shows that Fermented garlic (S-allyl cysteine,SAC,or black garlic extract, aged garlic extract) ameliorates the oxidative damage implicated in aging and a variety of diseases, such as cardiovascular alterations, cancer, stroke, Alzheimer’s disease (AD), and other age-related degenerative conditions. In addition, Fermented garlic (S-allyl cysteine,SAC,or black garlic extract, aged garlic extract) is a commercially available garlic preparation that has been widely studied for its high antioxidant content and its health-protective potential.
Pharmacokinetics of S-Allyl cysteine (SAC)
In rats, pharmacokinetics of SAC after oral administration shows a three-phase concentration profile: two very fast phases (absorption and distribution) followed by a slow elimination phase. For i.v. administration, SAC pharmacokinetics presents a two-phase concentration profile: a very fast distribution phase and a slow elimination phase [19, 20].
Oral bioavailability of SAC at 100 mg/kg dose is 91% , similar to that reported in other studies where bioavailability was 103.0% in mice, 98.2% in rats, and 87.2% in dogs .
In addition, a pharmacokinetic study of SAC in humans has been performed by oral administration of garlic preparation containing this compound. The half-life of SAC in humans after oral administration was more than 10 h, and clearance time was more than 30 h . These results are similar to experimental data obtained in dogs, where the half-life of SAC was about 10 h, and clearance time was more than 24 h, albeit these data were different from other experimental results obtained in mice . Total SAC content in the blood of volunteers at is about 450 μg (content on , 23 ng/mL plasma; body weight: 65 kg; volume of total blood: 1/3 of body weight), suggesting a high bioavailability in humans .
The antioxidant mechanism associated with the protective effects of SAC.
Antioxidant mechanism associated to S-allylcysteine (SAC). SAC can scavenge superoxide anion (), hydrogen peroxide (H2O2), hydroxyl radical (OH•), peroxynitrite radical (ONOO−), and peroxyl radical (LOO•) produced in neuronal cells, as well as hypochlorous acid (HOCl) and singlet oxygen (1O2) produced in microglial cells (blue lines). Moreover, SAC also exhibits chelating properties on Fe2+ and Cu2+ ions (red line), hence avoiding Fenton reaction. SAC also inhibits NF-kB translocation into the nucleus (green line), thus preventing apoptotic signaling. COX-2: cyclooxygenase-2, NOX: NADPH oxidase, nNOS: neuronal nitric oxide synthase, SOD: superoxide dismutase, XO: xanthine oxidase.
- Hahn, “History, folk medicine, and legendary uses of garlic,” in Garlic: The Science and Therapeutic Application of Allium Sativum L and Related Species, H. P. Koch and L. D. Lawson, Eds., pp. 1–24, Williams & Wilkins, Baltimore, Md, USA, 1996.
- Block, “The chemistry of garlic and onions.,” Scientific American, vol. 252, no. 3, pp. 114–119, 1985.
- D. Reuter, H. P. Koch, and L. D. Lawson, “Therapeutic effects of garlic and its preparations,” in Garlic: The Science and Therapeutic Application of Allium Sativum L and Related Species, H. P. Koch and L. D. Lawson, Eds., pp. 13–162, Williams & Wilkins, London, UK, 1996.
- D. Lawson, “Garlic: a review of its medicinal effects and indicated active compounds,” in Phytomedicines of Europe: Chemistry and Biological Activity, L. D. Lawson and R. Bauer, Eds., ACS Symposium Series 691, pp. 179–209, American Chemical Society, Washington, DC, USA, 1998.
- D. Lawson and C. D. Gardner, “Composition, stability, and bioavailability of garlic products used in a clinical trial,” Journal of Agricultural and Food Chemistry, vol. 53, no. 16, pp. 6254–6261, 2005.
- Amagase, B. L. Petesch, H. Matsuura, S. Kasuga, and Y. Itakura, “Intake of garlic and its bioactive components,” Journal of Nutrition, vol. 131, supplement 3, pp. 955S–962S, 2001.
- Aged Garlic Extract, Research Excerpts from Peer Reviewed Scientific Journals & Scientific Meetings, Wakunaga of America, Mission Viejo, Calif, USA, 2006.
- Ryu, N. Ide, H. Matsuura, and Y. Itakura, “Nα-(1-deoxy-D-fructos-1-yl)-L-arginine, an antioxidant compound identified in aged garlic extract,” Journal of Nutrition, vol. 131, supplement 3, pp. 972S–976S, 2001.
- Ichikawa, K. Ryu, J. Yoshida et al., “Antioxidant effects of tetrahydro-β-carboline derivatives identified in aged garlic extract,” BioFactors, vol. 16, no. 3-4, pp. 57–72, 2002.
- Ichikawa, J. Yoshida, N. Ide, T. Sasaoka, H. Yamaguchi, and K. Ono, “Tetrahydro-β-carboline derivatives in aged garlic extract show antioxidant properties,” Journal of Nutrition, vol. 136, supplement 3, pp. 726S–731S, 2006.
- Borek, “Antioxidant health effects of aged garlic extract,” Journal of Nutrition, vol. 131, no. 3, pp. 1010S–1015S, 2001.
- Ide and B. H. S. Lau, “Aged garlic extract attenuates intracellular oxidative stress,” Phytomedicine, vol. 6, no. 2, pp. 125–131, 1999.
- Ide and B. H. S. Lau, “Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-κ b activation,” Journal of Nutrition, vol. 131, supplement 3, pp. 1020S–1026S, 2001.
- M. Kim, S. B. Chun, M. S. Koo et al., “Differential regulation of NO availability from macrophages and endothelial cells by the garlic component S-allyl cysteine,” Free Radical Biology and Medicine, vol. 30, no. 7, pp. 747–756, 2001.
- Morihara, I. Sumioka, T. Moriguchi, N. Uda, and E. Kyo, “Aged garlic extract enhances production of nitric oxide,” Life Sciences, vol. 71, no. 5, pp. 509–517, 2002.
- Yamasaki and B. H. Lau, “Garlic compounds protect vascular endothelial cells from oxidant injury,” Nihon Yakurigaku Zasshi, vol. 110, pp. 138P–141P, 1997.
- A. Dillon, G. M. Lowe, D. Billington, and K. Rahman, “Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F2α in smoking and nonsmoking men and women,” Journal of Nutrition, vol. 132, no. 2, pp. 168–171, 2002.
- Kodera, A. Suzuki, O. Imada et al., “Physical, chemical, and biological properties of S-allylcysteine, an amino acid derived from garlic,” Journal of Agricultural and Food Chemistry, vol. 50, no. 3, pp. 622–632, 2002.
- K. Yan and F. D. Zeng, “Pharmacokinetics and tissue distribution of S-allylcysteine,” Asian Journal of Drug Metabolism and Pharmacokinetics, vol. 5, no. 1, pp. 61–69, 2005.
- Nagae, M. Ushijima, S. Hatono et al., “Pharmacokinetics of the garlic compound S-allylcysteine,” Planta Medica, vol. 60, no. 3, pp. 214–217, 1994.
- Jandke and G. Spiteller, “Unusual conjugates in biological profiles originating from consumption of onions and garlic,” Journal of Chromatography, vol. 421, no. 1, pp. 1–8, 1987.
- Ide, H. Matsuura, and Y. Itakura, “Scavenging effect of aged garlic extract and its constituents on active oxygen species,” Phytotherapy Research, vol. 10, no. 4, pp. 340–341, 1996.
- Numagami and S. T. Ohnishi, “S-allylcysteine inhibits free radical production, lipid peroxidation and neuronal damage in rat brain ischemia,” Journal of Nutrition, vol. 131, supplement 3, pp. 1100S–1105S, 2001.
- Yamasaki, L. Li, and B. H. S. Lau, “Garlic compounds protect vascular endothelial cells from hydrogen peroxide-induced oxidant injury,” Phytotherapy Research, vol. 8, no. 7, pp. 408–412, 1994.
- Ide and B. H. S. Lau, “Garlic compounds protect vascular endothelial cells from oxidized low density lipoprotein-induced injury,” Journal of Pharmacy and Pharmacology, vol. 49, no. 9, pp. 908–911, 1997.
- Imai, N. Ide, S. Nagae, T. Moriguchi, H. Matsuura, and Y. Itakura, “Antioxidant and radical scavenging effects of aged garlic extract and its constituents,” Planta Medica, vol. 60, no. 5, pp. 417–420, 1994.
- D. Maldonado, D. Barrera, I. Rivero et al., “Antioxidant S-allylcysteine prevents gentamicin-induced oxidative stress and renal damage,” Free Radical Biology and Medicine, vol. 35, no. 3, pp. 317–324, 2003.
- M. Kim, J. C. Lee, N. Chang, H. S. Chun, and W. K. Kim, “S-Allyl-l-cysteine attenuates cerebral ischemic injury by scavenging peroxynitrite and inhibiting the activity of extracellular signal-regulated kinase,” Free Radical Research, vol. 40, no. 8, pp. 827–835, 2006.
- N. Medina-Campos, D. Barrera, S. Segoviano-Murillo et al., “S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK1 cells of potassium dichromate-induced toxicity,” Food and Chemical Toxicology, vol. 45, no. 10, pp. 2030–2039, 2007.
- The Antioxidant Mechanisms Underlying the Aged Garlic Extract- and S-Allylcysteine-Induced Protection. Ana L. Colín-González,1 Ricardo A. Santana,1 Carlos A. Silva-Islas,1 Maria E. Chánez-Cárdenas,1 Abel Santamaría,2 and Perla D. Maldonado