Phytochemicals in Foods - 23 Health Benefits of S-allyl cysteine (SAC) (Organosulfides)

Home of Kyle J. Norton for The Better of Living & Living Health Sulfur represents approximately 1/4% of our total body weight and occurs principally in the body as a constituent of the cysteine and methionine. It plays an important role in protein synthesis and enzyme reaction functions and is found abundantly in broccoli, cauliflower, cabbage, kale, kohlrabi, etc.
Organosulfides
Organosulfur compounds presented in natural food are generally considered as beneficial for health because of their antioxidant and anticarcinogenic properties. This has led to their excessive and long-term consumption. However, there is also evidence that these compounds demonstrate toxicity and adverse health effects suggesting their potential dual biological roles. Thus, they can act as double-edged biological swords(a).
S-Allyl cysteine (SAC) is a natural compound found abundantly in fresh and aged garlic.
1. S-allylcysteine (SAC) on blood glucose
Strong evidence found that fresh garlic lowers blood glucose. In the study to evaluate the possible protective effects of S-allyl cysteine (SAC) on the antioxidant defense system of pancreas in streptozotocin(STZ) induced diabetes in rats by Bharathiyar University, Coimbatore, Tamilnadu, indicated that tlevels of glucose, TBARS and enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of SAC. The antidiabetic and antioxidant effect of SAC was compared with glyclazide, a well-known hypoglycemic drug(1).

2. S-allyl cysteine (SAC) and prostate cancer
According to the study to evaluate the effect of S-allylcysteine (SAC)on CWR22R, a human androgen-independent(AI) prostate cancer xenograft, in nude mice by the University of Hong Kong, showed that treatment with SAC resulted in inhibition of the growth of CWR22R, with no detectable
toxic effect on nude mice. The SAC-induced growth reduction was correlated with a concurrent reduction in serum PSA level and proliferation rate of xenografts, together with an inhibition of invasion through the restoration of E-cadherin and gamma-catenin expression. Furthermore, the apoptotic rate of SAC-treated tumours increased together with a decrease in Bcl-2 and increase in cleaved caspase-3(2).

3. S-allylcysteine in an acute myocardial infarction
S-allylcysteine (SAC) is an organosulfur-containing compound derived from garlic. According to the study by the National Univ. of Singapore, showed that SAC significantly lowered mortality (12.5% vs. 33.3%, P P P 2S levels and left ventricular cystathionine-γ-lyase (CSE) activities were analyzed to investigate the involvement of H₂S. CSE is the enzyme responsible for H₂S production in the heart. SAC increased left ventricular CSE activity in AMI rats (2.75 ± 0.34 vs. 1.23 ± 0.16 μmol·g protein⁻¹·h⁻¹; P −1·h⁻¹; P 2S concentration compared with controls and the SAC + PAG-treated group. Protein expression studies revealed that SAC upregulated CSE expression (1.1-fold of control; P P

4. S-Allylcysteine, a garlic-derived antioxidant
In the study to evaluate the effect of a garlic-derived compound and well-characterized free radical scavenger, S-allylcysteine, on quinolinic acid-induced striatal neurotoxicity and oxidative damage, by Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, showed that administration of 300 mg/kg of this compound to rats decreased effectively the quinolinic acid-induced oxidative injury measured as striatal reactive oxygen species formation (P S-Allylcysteine (300 mg/kg) also prevented the striatal decrease of copper/zinc-superoxide dismutase activity (P S-allylcysteine, at the same dose tested, was able to reduce the quinolinic acid-induced neurotoxicity evaluated as circling behavior (P S-allylcysteine ameliorates the in vivo quinolinate striatal toxicity by a mechanism related to its ability to: (a) scavenge free radicals; (b) decrease oxidative stress; and (c) preserve the striatal activity of Cu,Zn-superoxide dismutase (Cu,Zn-SOD)(4).

5. S-allylcysteine and diabetes
Iron may play a role in the pathogenesis of diabetes. In the study to investigate the effects of S-allylcysteine (SAC), a sulphur containing amino acid derived from garlic on the changes in iron metabolism induced by oxidative stress in tissues, as well as on serum biochemical parameters of streptozotocin (STZ)-induced diabetic rats by the Centre for Biological Science, K.S. Rangasamy College of Arts and Science, found that S-allylcysteine could have a protective effect against alterations in oxidative stress induced iron metabolism in the diabetic state which was evidenced by the capacity of this natural antioxidant to modulate parameters of iron metabolism(5).

6. S-allylcysteine (SAC) antioxidant mechanisms
Aged garlic extract (AGE) is an odorless garlic preparation containing S-allylcysteine (SAC) as its most abundant compound. According to the study to reviewed different antioxidant mechanisms (scavenging of free radicals and prooxidant species, induction of antioxidant enzymes, activation of Nrf2 factor, inhibition of prooxidant enzymes, and chelating effects) involved in the protective actions of AGE and SAC, thereby emphasizing their potential use as therapeutic agents. by Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, found that the original data shows the ability of SAC to activate Nrf2 factor in cerebral cortex and the therapeutic properties of these molecules comprise cellular and molecular mechanisms at different levels(6).

7. S-allylcysteine (SAC) and lipid profiles
In the study to examine the effect of high temperature/high pressure-processed garlic on plasma lipid profiles in rats, with Sprague-Dawley ratsfed a normal control diet, a high cholesterol (0.5% cholesterol) diet (HCD) only, or a high cholesterol diet supplemented with 0.5% high temperature/high pressure-processed garlic (HCP) or raw garlic (HCR) for 10 weeks, showed that the body weights of the rats fed the garlic-supplemented diets decreased, mostly because of reduced fat pad weights. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride (TG) in the HCP and HCR groups decreased significantly compared with those in the HCD group. Additionally, fecal TC and TG increased significantly in the HCP and HCR groups. It is notable that no significant differences in plasma or fecal lipid profiles were observed between the HCP and HCR groups. High temperature/high pressure-processed garlic contained a higher amount of S-allyl cysteine than raw garlic (P

8. S-allylcysteine (SAC) and Liver cancer
In the study to investigate the effect of a garlic derivative, S-allylcysteine (SAC), on the proliferation and metastasis of Hepatocellular carcinoma (HCC), indicated that the proliferation rate and colony-forming abilities of MHCC97L cells were suppressed by SAC together with significant suppression of the expressions of proliferation markers, Ki-67 and proliferating cell nuclear antigen (PCNA). Moreover, SAC hindered the migration and invasion of MHCC97L cells corresponding with up-regulation of E-cadherin and down-regulation of VEGF. Furthermore, SAC significantly induced apoptosis and necrosis of MHCC97L cells through suppressing Bcl-xL and Bcl-2 as well as activating caspase-3 and caspase-9. In addition, SAC could significantly induce the S phase arrest of MHCC97L cells together with down-regulation of cdc25c, cdc2 and cyclin B1(8).

9. S-allylcysteine (SAC) and neurologic deficit
In the study to examine the hypothesis of S-allyl cysteine (SAC), organosulfur compounds found in garlic extract, would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO), found that S-allyl cysteine treatment significantly reduced ischemic lesion volume, improved neurologic deficits, combated oxidative loads, and suppressed neuronal loss. Behavioral and biochemical alterations observed after MCAO were further associated with an increase in glial fibrillary acidic protein and inducible nitric oxide expression and were markedly inhibited by the treatment with SAC(9).

10. S-Allylcysteine inhibits Oral tumour progression
Studies have indicated that an increase in the osteopontin (OPN) plasma level is correlated with the progression of oral cancer. According to the study by the Taipei Medical University, the SAC-mediated suppression of cyclin D1 protein was associated with an augmented expression of the cell-cycle inhibitor p16(Ink4). Furthermore, SAC inhibited the expression of cyclo-oxygenase-2, vimentin and NF-κB p65 (RelA)(10).

11. S-Allylcysteine and Non-Small-Cell Lung Carcinoma
Lung cancer is one of the leading causes of cancer death in the world. Human non-small-cell lung carcinoma (NSCLC) accounts for almost 80% of lung cancer cases. According to the study of Consumption of S-Allylcysteine Inhibits the Growth of Human Non-Small-Cell Lung Carcinoma in a Mouse Xenograft Model, by the China Medical University, SAC significantly suppressed the activation of mTOR, NF-κB, and cyclin D1 molecules in vitro. Furthermore, the results demonstrated that consumption of SAC significantly inhibited the growth of highly metastatic human NSCLC cells in tumor-bearing mice. Bioluminescence imaging and pathological and immunohistochemical (IHC) staining results also indicated that SAC could effectively suppress the growth and malignant progression of human NSCLC in vivo. The chemopreventive effects of SAC were associated with suppression of mTOR and NF-κB molecules in vivo(11).

12. S-allyl-L-cysteine (SAC) and Alzheimer’s disease (AD)
Alzheimer’s disease (AD) is the most common form of dementia in the older people and 7(th) leading cause of death in the United States. Deposition of amyloid-beta (Aβ) plaques, hyperphosphorylation of microtubule associated protein tau (MAPT), neuroinflammation and cholinergic neuron loss are the major hallmarks of AD. According to the study by the Indiana University School of Medicine, apart from its culinary use, garlic (Allium sativum) is being used to treat several ailments like cancer and diabetes. A specific ‘Aged Garlic Extract’ (AGE) and one of its active ingredients, S-allyl-L-cysteine (SAC) may be potental in restricting several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD(12).

13. S-allyl-L-cysteine (SAC) Neuroprotective effect
Neuronal apoptosis is one of the pathological features of Alzheimer’s disease (AD) and is associated with senile plaques containing amyloid-b peptide (Abeta). According to the study of Neuroprotective effect of garlic compounds in amyloid-beta peptide-induced apoptosis in vitro, by Loma Linda University, aged garlic extract (AGE) and S-allyl-L-cysteine (SAC) not only suppressed the generation of ROS but also attenuated caspase-3 activation, DNA fragmentation, PARP cleavage and eventually protected against Ab-induced apoptosis(13).

14. S-Allylcysteine (SAC) and parkinsonism
S-Allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract, has multifunctional activity via different mechanisms and neuroprotective effects that are exerted probably via its antioxidant or free radical scavenger action. According to the study by National Institute of Neurology and Neurosurgery, “Manuel Velasco Suárez,” SS, Mexico City, neuroprotective effect of SAC against MPP(+) neurotoxicity was associated with blocked (100% of protection) of lipid peroxidation and reduction of superoxide radical production – indicated by an up-regulation of Cu-Zn-superoxide dismutase activity – both of which are indices of oxidative stress. Behavioral analyses showed that SAC improved MPP(+)-induced impairment of locomotion (35%). These findings suggest that in mice, SAC attenuates MPP(+)-induced neurotoxicity in the striatum and that an antioxidant effect against oxidative stress may be partly responsible for its observed neuroprotective effects(14).

15. S-Allylcysteine (SAC) antihypertensive and cardioprotective effects
In the study to investigate the role of fresh garlic homogenate (FGH) and its bioactive sulphur compound S-allyl cysteine sulphoxide (SACS) in potentiating antihypertensive and cardioprotective activities of captopril in rats, showed that combined therapy of garlic (250 mg/kg) with captopril(CAP) demonstrated higher synergistic action than combination of SACS (0.222 mg/kg) with CAP suggesting the role of additional bioactive constituents apart from SACS, responsible for therapeutic efficacy of garlic. Moreover, combination of SACS and CAP exerted super-additive (synergistic) interaction with respect to fall in blood pressure and ACE inhibition(15).

16. S-Allylcysteine (SAC) and hepatic fibrosis
Hepatic fibrosis is a chronic progressive disorder with a poor prognosis for which no definitive treatment exists. According to the study of S-allylcysteine is effective as a chemopreventive agent against porcine serum-induced hepatic fibrosis in rats, by Osaka City University, oral administration of SAC reduced PS-induced hepatic fibrosis in rats via inhibition of HSC activation. SAC could provide a new therapeutic strategy for hepatic fibrosis(16).

17. S-Allylcysteine (SAC) and human breast-cancer
In the study to investigate the effect of aged garlic extract (AGE) and two of its components, S-allylcysteine (SAC), and S-allyl-mercaptocysteine (SAMC) on human breast cancer cells, MCF-7 and MCF-7(ras)., showed that anti-proliferative response to SAC and SAMC on both anchorage dependent and independent conditions and an alteration in glutathione level without significant concurrent changes in the glutathione metabolizing enzymes(17).

18. S-allylcysteine (SAC) and Colon cancer
In the study to examine two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, showed that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of the compound sulindac sulfide (SS). SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of the compound sulindac sulfide (SS), with SAMC enhanced the growth inhibitory and apoptotic effects of SS(18).

19. Ameliorative effect of S-allylcysteine (SAC)
In the study to examine the effect of S:-allylcysteine (SAC), a major thioallyl compound found in aged garlic extract, on the memory deficit and age-related changes of senescence-accelerated mice fed a diet supplemented with 40 mg SAC/kg diet for 8 mo, showed that chronic dietary treatment with 40 mg SAC/kg diet decreased the time in the open arm in senescence-accelerated prone P10 mice. These studies suggest that diet supplementation with SAC may reduce age-related learning disabilities and cognitive disorders in senescence-accelerated mice(19).

20. S-allylcysteine (SAC) and renal protective effect
Acute renal failure (ARF) is a major complication of gentamicin (GM) treatment, which is effective against gram-negative infections. According to the study by Universidad Nocional Autonoma de Mexico, ARF was evident of the alterations of(i) decrease in creatinine clearance and increase in blood urea nitrogen, (ii) decrease in blood glutathione peroxidase (GPx) activity and increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein, and (iii) necrosis of proximal tubular cells were prevented by SAC treatment (250 mg/kg/i.p. 24 h before the first dose of GM and 125 mg/kg/12 h/4 days along GM-treatment). Furthermore, SAC prevented the GM-induced oxidative stress (protein carbonyl groups) and the decrease in manganese superoxide dismutase (Mn-SOD), GPx, and glutathione reductase (GR) activities in renal cortex(20).

21. Combination of S-allylcysteine and lycopene in gastric cancer
Combination chemoprevention by diet-derived agents that induce apoptosis is a promising strategy to control gastric cancer, the second most common malignancy worldwide According to the study by Annamalai University, although SAC and lycopene alone significantly suppressed the development of gastric cancer, administration of SAC and lycopene in combination was more effective in inhibiting MNNG-induced stomach tumours and modulating the expression of apoptosis-associated proteins(21).

22. S-allyl cysteine (SAC) and pulmonary fibrosis
In the study to examine the effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats with CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks, showed that SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses(22).

23. S-allyl cysteine (SAC) and bladder hemorrhagic cystitis
S-Allylcysteine (SAC), an organosulfur compound of aged garlic extract (AGE) regulates the thiol status of the cell and scavenges free radicals. According to the study by Hamdard University, SAC not only showed protection in tissue histology but also improved the decreased activities of antioxidant enzymes.SAC treatment also reduced LPO and increased GSH levels. Although SAC treatment did not ensure full recovery, the marked improvement in histology and antioxidants of bladder suggests that it has a significant modulatory effect on CP-induced urotoxicity. Since decrease in antioxidant level is the major cause of CP urotoxicity, the protective effect of SAC deserves its further exploration involving laboratory and clinical investigations(23).

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