s-allylcysteine and alliin

Topics: Allium; Animals; Anti-Infective Agents; Antineoplastic Agents; Blood Platelets; Cysteine; Disulfides; Fibrinolysis; Garlic; Humans; Immunologic Factors; Neoplasms; Obesity; Phytochemicals; Plant Extracts; Solubility; Sulfoxides; Sulfur; Sulfur Compounds

S‑allyl‑cysteine sulfoxide (alliin) is the main organosulfur component of garlic and its preparations. The present study aimed to examine the protective effect of alliin on cardiac function and the underlying mechanism in a mouse model of myocardial infarction (MI). Notably, alliin treatment preserved heart function, attenuated the area of infarction in the myocardium of mice and reduced lesions in the myocardium, including cardiomyocyte fibrosis and death. Further mechanistic experiments revealed that alliin inhibited necroptosis but promoted autophagy in vitro and in vivo. Cell viability assays showed that alliin dose‑dependently reduced the necroptotic index and inhibited the expression of necroptosis‑related receptor‑interacting protein 1, receptor‑interacting protein 3 and tumor necrosis factor receptor‑associated factor 2, whereas the levels of Beclin 1 and microtubule‑associated protein 1 light chain 3, which are associated with autophagy, exhibited an opposite trend upon treatment with alliin. In addition, the level of peroxisome proliferator‑activated receptor γ was increased by alliin. Collectively, these findings demonstrate that alliin has the potential to protect cardiomyocytes from necroptosis following MI and that this protective effect occurs via the enhancement of autophagy.

Topics: Animals; Apoptosis; Autophagy; Cell Survival; Cysteine; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Necroptosis; Receptor-Interacting Protein Serine-Threonine Kinases; Safrole; Signal Transduction

Different types of sulfur compounds, namely S-allyl-L-cysteine (SAC), S-allyl-L-cysteine sulfoxide (ACSO) and a synthetic γ-L-glutamyl-S-allyl-L-cysteine (GSAC) were extracted from black garlic and their inhibition to the advanced glycation end-products (AGEs) were investigated. Upon addition of inhibitor, the amount of produced fructosamine was determined by UV visible spectroscopy. The change of pentosidine and fluorescent AGEs during reaction was detected by fluorescence method and the change of carboxymethyl lysine (CML) was detected by high performance liquid chromatography. It was found that the inhibitory effects of SAC and ACSO are stronger to the early and mid non-fluorescent products in glycosylation reaction, and GSAC has an obvious inhibitory effect on the later reaction products. All these three inhibitors can effectively inhibit advanced glycation reaction. Although their effects on glycation products are different due to different chemical structures, they have similar inhibitory effects on fluorescent products.

Topics: Antioxidants; Cysteine; Dipeptides; Fermentation; Garlic; Sulfur Compounds

S-Allylcysteine (SAC) is a key component of aged garlic extract, one of many garlic products. However, information on its pharmacokinetics has been scant except for data from a few animal studies.. We designed this study to determine the overall pharmacokinetics of SAC in rats.. After oral or intravenous administration of SAC to rats at a dose of 5 mg/kg, the plasma concentration-time profile of SAC and its metabolites, as well as the amounts excreted in bile and urine, were analyzed by using liquid chromatography tandem mass spectrometry.. After oral administration, SAC was well absorbed with a bioavailability of 98%. Two major metabolites of SAC, N-acetyl-S-allylcysteine (NAc-SAC) and N-acetyl-S-allylcysteine sulfoxide (NAc-SACS), were detected in plasma, but their concentrations were markedly lower than those of SAC. SAC was metabolized to a limited extent, but most of the orally absorbed SAC was excreted into urine in the form of its N-acetylated metabolites. The amounts of SAC, NAc-SAC, and NAc-SACS excreted in urine over 24 h were 2.9%, 80%, and 11% of the orally administered SAC, respectively. The very low renal clearance (0.016 L ⋅ h(-1) ⋅ kg(-1)) of SAC indicated that it undergoes extensive renal reabsorption. These results collectively suggested that SAC was ultimately metabolized to NAc-SAC and NAc-SACS through the cycles of urinary excretion, renal reabsorption, and systemic recirculation.. The pharmacokinetics of SAC in rats were characterized by high oral absorption, limited metabolism, and extensive renal reabsorption, all of which potentially contribute to its high and relatively long-lasting plasma concentrations.

Topics: Acetylation; Administration, Oral; Animals; Bile; Biological Availability; Cysteine; Garlic; Intestinal Absorption; Male; Plant Extracts; Rats, Sprague-Dawley; Renal Reabsorption

S-Alk(en)yl-l-cysteine sulfoxides are cysteine-derived secondary metabolites highly accumulated in the genus Allium. Despite pharmaceutical importance, the enzymes that contribute to the biosynthesis of S-alk-(en)yl-l-cysteine sulfoxides in Allium plants remain largely unknown. Here, we report the identification of a flavin-containing monooxygenase, AsFMO1, in garlic (Allium sativum), which is responsible for the S-oxygenation reaction in the biosynthesis of S-allyl-l-cysteine sulfoxide (alliin). Recombinant AsFMO1 protein catalyzed the stereoselective S-oxygenation of S-allyl-l-cysteine to nearly exclusively yield (RC SS )-S-allylcysteine sulfoxide, which has identical stereochemistry to the major natural form of alliin in garlic. The S-oxygenation reaction catalyzed by AsFMO1 was dependent on the presence of nicotinamide adenine dinucleotide phosphate (NADPH) and flavin adenine dinucleotide (FAD), consistent with other known flavin-containing monooxygenases. AsFMO1 preferred S-allyl-l-cysteine to γ-glutamyl-S-allyl-l-cysteine as the S-oxygenation substrate, suggesting that in garlic, the S-oxygenation of alliin biosynthetic intermediates primarily occurs after deglutamylation. The transient expression of green fluorescent protein (GFP) fusion proteins indicated that AsFMO1 is localized in the cytosol. AsFMO1 mRNA was accumulated in storage leaves of pre-emergent nearly sprouting bulbs, and in various tissues of sprouted bulbs with green foliage leaves. Taken together, our results suggest that AsFMO1 functions as an S-allyl-l-cysteine S-oxygenase, and contributes to the production of alliin both through the conversion of stored γ-glutamyl-S-allyl-l-cysteine to alliin in storage leaves during sprouting and through the de novo biosynthesis of alliin in green foliage leaves.

Topics: Cloning, Molecular; Cysteine; Cytosol; Dipeptides; Garlic; Gene Expression Regulation, Plant; Green Fluorescent Proteins; Molecular Sequence Data; Oxygenases; Phylogeny; Plant Leaves; Plant Proteins; Recombinant Proteins; Substrate Specificity

Naturally occurring (+)-trans-isoalliin, (R(C)R(S))-(+)-trans-S-1-propenyl-L-cysteine sulfoxide, is a major cysteine sulfoxide in onion. The importance of producing it synthetically to support further research is very well recognized. The (+)-trans-isoalliin is prepared by chemical synthesis and reversed-phase (RP)-HPLC. First, S-2-propenyl-L-cysteine (deoxyalliin) is formed from L-cysteine and allyl bromide, which is then isomerized to S-1-propenyl-L-cysteine (deoxyisoalliin) by a base-catalyzed reaction. A mixture of cis and trans forms of deoxyisoalliin is formed and separated by RP-HPLC. Oxidation of the trans form of deoxyisoalliin by H2O2 produces a mixture of (-)- and (+)-trans-isoalliin. Finally, RP-HPLC is used successfully in separating (-)- and (+)-trans-isoalliin, and hence, (+)-trans-isoalliin is synthesized for the first time in this study. In addition, the (±) diastereomers of cis-isoalliin are also separated and purified by RP-HPLC.

Topics: Allyl Compounds; Catalysis; Chromatography, High Pressure Liquid; Cysteine; Hydrogen Peroxide; Isomerism; Onions; Safrole

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

Garlic and garlic extracts, through their antioxidant activities, have been reported to provide protection against free radical damage in the body. This study investigated antioxidant properties of garlic compounds representing the four main chemical classes, alliin, allyl cysteine, allyl disulfide, and allicin, prepared by chemical synthesis or purification. Alliin scavenged superoxide, while allyl cysteine and allyl disulfide did not react with superoxide. Allicin suppressed the formation of superoxide by the xanthine/xanthine oxidase system, probably via a thiol exchange mechanism. Alliin, allyl cysteine, and allyl disulfide all scavenged hydroxyl radicals; the rate constants calculated based on deoxyribose competitive assay were 1.4-1.7 x 10(10), 2.1-2.2 x 10(9), and 0.7-1.5 x 10(10) M (1) second(1), respectively. Contrary to previous reports, allicin did not exhibit hydroxyl radical scavenging activity in this study. Alliin, allicin, and allyl cysteine did not prevent induced microsomal lipid peroxidation, but both alliin and allyl cysteine were hydroxyl scavengers, and allyl disulfide was a lipid peroxidation terminator. In summary, our findings indicated that allyl disulfide, alliin, allicin, and allyl cysteine exhibit different patterns of antioxidant activities as protective compounds against free radical damage.

Topics: Allyl Compounds; Antioxidants; Cysteine; Disulfides; Free Radical Scavengers; Garlic; Hydrogen Peroxide; Hydroxyl Radical; Lipid Peroxidation; Sulfinic Acids; Superoxides

The path of synthesis of alkyl cysteine sulphoxides, or flavour precursors, in the Alliums is still speculative. There are two proposed routes for alliin biosynthesis, one is from serine and allyl thiol while the other is from glutathione and an allyl source via gamma glutamyl peptides. The routes have been investigated by exposing undifferentiated callus cultures of garlic and onion to potential pathway intermediates. After a period of incubation of 2 days the callus was extracted, and analysed for flavour precursors and related compounds by HPLC. Standards of alliin, isoallin and propiin were synthesised and their identity confirmed by HPLC and NMR. Putative intermediates selected included the amino acids serine and cysteine, as well as more complex intermediates such as allylthiol, allyl cysteine and glutathione. Both garlic and onion tissue cultures were able to synthesize alliin following incubation with allylthiol, and cysteine conjugates such as allyl cysteine. The ability of the tissue cultures to form alliin from intermediates was compatible with the proposed routes of synthesis of alliin.

Topics: Cysteine; Garlic; Onions; Tissue Culture Techniques

Although extracts of garlic inhibit cholesterol biosynthesis in cultured hepatocytes, the inhibitory components of garlic and the site or sites of inhibition in the cholesterol biosynthetic pathway have not been established. To elucidate potential mechanisms of inhibition, we examined the effect of fresh garlic extract and 16 water- or lipid-soluble compounds derived from garlic on purified recombinant human squalene monooxygenase. Squalene monooxygenase catalyzes the second and likely rate-limiting step in the downstream pathway for cholesterol biosynthesis. A 50% inhibitory concentration (IC(50)) of squalene epoxidation was achieved with 1 g/L of fresh garlic extract; of the 16 garlic compounds tested, only selenocystine (IC(50) = 65 micromol/L), S-allylcysteine (IC(50) = 110 micromol/L), alliin (IC(50) = 120 micromol/L), diallyl trisulfide (IC(50) = 195 micromol/L), and diallyl disulfide (IC(50) = 400 micromol/L) substantially inhibited the enzyme. Kinetic analysis showed that the inhibition by garlic and by these compounds was slow and irreversible, suggestive of covalent binding to the enzyme; the ability of thiol-containing compounds such as glutathione and 2,3-dimercaptopropanol to prevent and reverse the inhibition indicated that the garlic compounds were reacting with sulfhydryl groups on the protein. Dithiols were better reversal agents than monothiols, further suggesting that these inhibitors bind to the proposed vicinal sulfhydryls present on this enzyme. These results indicate that squalene monooxygenase may be one of the target enzymes through which garlic inhibits cholesterol biosynthesis.

Topics: Cysteine; Cystine; Cytochrome P-450 Enzyme Inhibitors; Dimercaprol; Dithiothreitol; Dose-Response Relationship, Drug; Garlic; Glutathione; Humans; Organoselenium Compounds; Oxygenases; Plant Extracts; Plants, Medicinal; Squalene Monooxygenase

Several organosulfur compounds found in garlic extract promoted the survival of rat hippocampal neurons in vitro. From the analysis of structure-activity relationship, thioallyl group in these compounds is essential for the manifestation of neurotrophic activity. S-Allyl-L-cysteine (SAC), one of the organosulfur compounds having thioallyl group in garlic extract, also promoted the axonal branching of cultured neurons. These results suggest that thioallyl compounds make a unique group of neurotrophic factors.

Topics: Animals; Cell Division; Cell Survival; Cells, Cultured; Cysteine; Embryo, Mammalian; Garlic; Hippocampus; Nerve Growth Factors; Neurons; Plants, Medicinal; Rats; Rats, Wistar; Sulfur