s-allylcysteine and allyl-sulfide

Garlic in different forms has antioxidant properties. These properties are shown to be due to the existence of compounds such as water soluble organosulfur compounds, S-allylcysteine and lipid soluble compounds like diallyl sulfide. The in vivo and in vitro ischemia reperfusion studies showed that prophylactic administration of aqueous garlic prior to ischemia reperfusion inhibit lipid peroxidation and prevent depletion in glutathione through its compounds that led to functional recovery. Its ability to inhibit neutrophil migration could suppress fibrosis formation. These preventive effects are seen in models that studied organs such as kidney and liver with functional recovery. Organ system specific activity such as angiotensin converting enzyme-inhibiting activity contributes to a cardioprotective and blood pressure lowering effect. Future studies should focus on post ischemia reperfusion administration of garlic to explore its rescue potential rather than prophylactic impact. Bench research findings should be translated into clinical use through human studies.

Topics: Allyl Compounds; Antioxidants; Brain Ischemia; Cysteine; Garlic; Glutathione; Humans; Kidney; Lipid Peroxidation; Liver; Myocardial Reperfusion Injury; Phytotherapy; Reperfusion Injury; Sulfides

The anti-neuroinflammatory capacities of raw and steamed garlic extracts as well as five organosulfur compounds (OSCs) were examined in lipopolysaccharide (LPS)-stimulated BV2 microglia. According to those results, steaming pretreatment blocked the formation of alliinase-catalyzed OSCs such as allicin and diallyl trisulfide (DATS) in crushed garlic. Raw garlic, but not steamed garlic, dose-dependently attenuated the production of LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1). DATS and diallyl disulfide at 200 and 400 μM, respectively, displayed significant anti-neuroinflammatory activity. Meanwhile, even at 1 mM, diallyl sulfide, S-allyl cysteine and alliin did not display such activity. Inhibition of nuclear factor-κB activation was the mechanism underlying this protective effect of raw garlic and DATS. Analysis results indicated that the anti-neuroinflammatory capacity of raw garlic is due to the alliin-derived OSCs. Importantly, DATS is a highly promising therapeutic candidate for treating inflammation-related neurodegenerative diseases.

Topics: Allium; Allyl Compounds; Animals; Cell Line; Chemokine CCL2; Cysteine; Disulfides; Garlic; Inflammation; Interleukin-1beta; Lipopolysaccharides; Mice; Microglia; Neurodegenerative Diseases; NF-kappa B; Nitric Oxide; Plant Extracts; Sulfides; Sulfur Compounds; Tumor Necrosis Factor-alpha

Allyl sulfides undergo efficient cross-metathesis in aqueous media with Hoveyda-Grubbs second generation catalyst 1. The high reactivity of allyl sulfides in cross-metathesis was exploited in the first examples of cross-metathesis on a protein surface. S-Allylcysteine was incorporated chemically into the protein, providing the requisite allyl sulfide handle. Preliminary efforts to genetically incorporate S-allylcysteine into proteins are also reported.

Topics: Allyl Compounds; Bacillus; Bacterial Proteins; Cysteine; Escherichia coli; Glucosidases; Methionine; Models, Molecular; Subtilisin; Sulfides; Water

The aim of this study was to assess the antigenotoxic activity of several garlic organosulfur compounds (OSC) in the human hepatoma cell line HepG2, using comet assay. The OSC selected were allicin (DADSO), diallyl sulfide (DAS), diallyl disulfide (DADS), S-allyl cysteine (SAC) and allyl mercaptan (AM). To explore their potential mechanisms of action, two approaches were performed: (i) a pre-treatment protocol which allowed study of the possible modulation of drug metabolism enzymes by OSC before treatment of the cells with the genotoxic agent; (ii) a co-treatment protocol by which the ability of OSC to scavenge direct-acting compounds was assessed. Preliminary studies showed that, over the concentration range tested (5-100 microM), the studied OSC neither affected cell viability nor induced DNA damage by themselves. In the pre-treatment protocol, aflatoxin B1 genotoxicity was significantly reduced by all the OSC tested except AM. DADS was the most efficient OSC in reducing benzo(a)pyrene genotoxicity. SAC and AM significantly decreased DNA breaks in HepG2 cells treated with dimethylnitrosamine. Additionally, all the OSC studied were shown to decrease the genotoxicity of the direct-acting compounds, hydrogen peroxide and methyl methanesulfonate. This study demonstrated that garlic OSC displayed antigenotoxic activity in human metabolically competent cells.

Topics: Aflatoxin B1; Allyl Compounds; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Cysteine; Disulfides; DNA Damage; Garlic; Humans; Liver Neoplasms; Mutagens; Sulfhydryl Compounds; Sulfides; Sulfinic Acids; Sulfur Compounds

It was shown that aged garlic extract (AGE), garlic powder and the following garlic-derived compounds: S-allylcysteine (SAC), diallyl sulfide (DAS) and diallyl disulfide (DADS), ameliorate gentamicin (GM)-induced nephrotoxicity in rats. However, it was not established if the above mentioned extracts and compounds of garlic could interfere with the antibiotic action of GM. To address this point, AGE, garlic powder extract (GPE), SAC, DAS and DADS were assessed for their ability to interfere with the in vitro antibiotic activity of GM in Escherichia coli cultures. It was found that the above mentioned extracts and compounds of garlic were unable to decrease the antibiotic capacity of GM and even SAC, DAS and DADS alone inhibited the growth of Escherichia coli and enhanced the antibiotic effect of GM. Our data show that SAC, DAS and DADS are antibacterial compounds against E. coli and suggest that AGE, GPE, SAC, DAS and[sol ]or DADS may be administered along with GM-treatment to ameliorate GM-induced nephrotoxicity without interfering with its antibiotic activity.

Topics: Allyl Compounds; Anti-Bacterial Agents; Cysteine; Disulfides; Drug Interactions; Escherichia coli; Garlic; Gentamicins; Humans; Microbial Sensitivity Tests; Phytotherapy; Plant Extracts; Protective Agents; Sulfides

Excessive nitric oxide (NO) production is involved in cellular injury and possibly in the multistage process of carcinogenesis. In this study, we investigated the effect of organosulfur compounds (S-allyl cysteine, allyl sulfide, diallyl disulfide, allyl isothiocyanate, phenyl isothiocyanate, and benzyl isothiocyanate) that are found in allium or cruciferous vegetables on NO production in J774.1 macrophages activated with lipopolysaccharide (LPS). Diallyl disulfide, allyl, phenyl, and benzyl isothiocyanates inhibited NO production, as evaluated by nitrite formation at 25 microM. Allyl and benzyl isothiocyanates, the most active of the six organosulfur compounds, exhibited dose-dependent inhibition and had IC(50) values of 1.6 and 2.7 microM, respectively. Western blot analysis suggested that suppression of the induction of inducible NO synthase (iNOS) expression is responsible for the inhibition of NO production by allyl and benzyl isothiocyanates. In contrast, these isothiocyanates increased LPS-stimulated tumor necrosis factor alpha (TNF-alpha) release, suggesting their selective action on genes activated by LPS. Our results demonstrate that certain organosulfur compounds inhibit NO synthesis in LPS-activated macrophages, and the inhibitory effect may be a significant component of their anticarcinogenic activity.

Topics: Allyl Compounds; Animals; Cells, Cultured; Cysteine; Drug Interactions; Gene Expression; Isothiocyanates; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Sulfides; Sulfur Compounds; Tumor Necrosis Factor-alpha

Various components of garlic and aged garlic extract, including allicin, S-allylcysteine (SAC) and volatile metabolites of allicin were determined in breath, plasma and simulated gastric fluids by HPLC, gas chromatography (GC) or HPLC- and GC-mass spectrometry (MS). Data indicate that allicin decomposes in stomach acid to release allyl sulfides, disulfides and other volatiles that are postulated to be metabolized by glutathione and/or S-adenosylmethionine to form allyl methyl sulfide. SAC can be absorbed by the body and can be determined in plasma by HPLC or HPLC-MS using atmospheric pressure chemical ionization (APCI)-MS.

Topics: Allyl Compounds; Breath Tests; Chromatography, Gas; Chromatography, High Pressure Liquid; Cysteine; Disulfides; Garlic; Gas Chromatography-Mass Spectrometry; Gastrointestinal Contents; Glutathione; Humans; Plant Extracts; Plants, Medicinal; S-Adenosylmethionine; Sulfides; Sulfinic Acids

Effects of an aged garlic extract and its thioallyl components on rat brain ischemia were examined using a middle cerebral artery occlusion model and a transient global ischemia model. In focal ischemia, an aged garlic extract, S-allyl cysteine (SAC), Allyl sulfide (AS) or Allyl disulfide (ADS) was administered 30 min prior to ischemic insult. Three days after ischemic insult, water contents of both ischemic and contralateral hemispheres were measured to assess the degree of ischemic damage. The water content of the ischemic control (no drug treatment) group was 81.50 +/- 0.07% (mean +/- SEM). It was significantly reduced with the administration of 300 mg/kg of SAC; the water content was 80.66 +/- 0.11% (P < 0.001). The histological observation using 2,3,5-triphenyltetrazolium chloride staining demonstrated that the administration of SAC reduced infarct volume. Neither AS nor ADS was effective. In global ischemia, the production of reactive oxygen species (ROS) was measured ex vivo using a spin-trapping agent, alpha-phenyl-N-tert-butylnitrone, and electron paramagnetic resonance spectroscopy. The production of ROS had two peaks; first at 5 min and second at 20 min after reperfusion. Both SAC and 7-nitro indazole, a nitric oxide synthase inhibitor, did not attenuate the amount of ROS produced at the first peak, but did the amount of the second peak. A possible involvement of peroxinitrite, which may be formed from superoxide and nitric oxide and is known to be highly toxic in ischemia/reperfusion injury of the brain, was suggested.

Topics: Allyl Compounds; Animals; Antioxidants; Body Water; Brain; Brain Diseases; Cysteine; Electron Spin Resonance Spectroscopy; Free Radicals; Garlic; Ischemic Attack, Transient; Male; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Sulfides; Time Factors

Six organosulfur compounds found in garlic were examined for their ability to alter the growth of canine mammary tumor cells (CMT-13) in culture. Water-soluble organosulfur compounds (S-allyl-cysteine, S-ethyl-cysteine and S-propyl-cysteine) did not significantly alter the growth of CMT-13 cells when added to cultures at 1.0 mM or less. However, oil-soluble organosulfur compounds (diallyl sulfide, diallyl disulfide and diallyl trisulfide) markedly inhibited growth. Increasing addition of diallyl disulfide (DADS) resulted in a progressive decrease in CMT-13 cell growth. Addition of glutathione before DADS markedly decreased the severity of the growth inhibition. Treatment with DL-buthionine-SR-sulfoxamine, a specific inhibitor of glutathione synthesis, accentuated the growth inhibition caused by DADS. These studies show that some organosulfur compounds found in garlic are effective inhibitors of the growth of the neoplastic CMT-13 cell. The inhibitory effects of these compounds are modified by intracellular glutathione.

Topics: Allyl Compounds; Analysis of Variance; Animals; Anticarcinogenic Agents; Cell Division; Cysteine; Disulfides; Dogs; Female; Garlic; Glutathione; Growth Inhibitors; Mammary Neoplasms, Experimental; Plant Oils; Plants, Medicinal; Sulfides; Sulfur; Tumor Cells, Cultured