S-allylcysteine Research Articles

S-allylcysteine induces cytotoxic effects in two human lung cancer cell lines via induction of oxidative damage, downregulation of Nrf2 and NF-κB, and apoptosis.

In this study, we investigated the putative cytotoxic effect elicited by the garlic-derived compound S-allylcysteine (SAC) in two human cancer cell lines (HCC827 and NCI-H1975) in order to develop an experimental approach to the therapeutic potential of this molecule for lung cancer. Cells were incubated for 24, 48 and 72 h in the presence of SAC (10 or 20 mM), which resulted in a concentration- and time-dependent decrease in cell viability and culture confluence in both cell lines. These effects were contrasted with - and validated through - those observed in an immortalized but nontumorigenic epithelial cell line from human bronchial epithelium (BEAS-2B, negative control) and an adenocarcinoma human alveolar basal epithelial cell line (A549, positive control). SAC (20 mM at 72 h) also increased the oxidative damage to lipids, augmented apoptosis, and decreased the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappa B (NF-κB) proteins in HCC827 and NCI-H1975 cells. Our results establish the efficacy of SAC in reducing malignant growth and proliferation of lung tumor cells. This effect is mediated by the induction of oxidative damage associated with the downregulation of Nrf2 and NF-κB and their corresponding signaling pathways.

S-allyl cysteine reduces osteoarthritis pathology in the tert-butyl hydroperoxide-treated chondrocytes and the destabilization of the medial meniscus model mice via the Nrf2 signaling pathway.

In this study, we used murine chondrocytes as an in vitro model and mice exhibiting destabilization of the medial meniscus (DMM) as an in vivo model to investigate the mechanisms through which S-allyl cysteine (SAC) alleviates osteoarthritis (OA). SAC significantly reduced apoptosis and senescence and maintained homeostasis of extracellular matrix (ECM) metabolism in tert-butyl hydroperoxide (TBHP)-treated chondrocytes. Molecular docking analysis showed a –CDOCKER interaction energy value of 203.76 kcal/mol for interactions between SAC and nuclear factor erythroid 2-related factor 2 (Nrf2). SAC increased the nuclear translocation of Nrf2 and activated the Nrf2/HO1 signaling pathway in TBHP-treated chondrocytes. Furthermore, Nrf2 knockdown abrogated the antiapoptotic, antisenescence, and ECM regulatory effects of SAC in TBHP-treated chondrocytes. SAC treatment also significantly reduced cartilage ossification and erosion, joint-space narrowing, synovial thickening and hypercellularity in DMM model mice. Collectively, these findings show that SAC ameliorates OA pathology in TBHP-treated chondrocytes and DMM model mice by activating the Nrf2/HO1 signaling pathway.

Protective Effect of S-Allyl Cysteine Against Neonatal Asthmatic Rats.

S-Allyl cysteine (SAC), an organic compound and a natural constituent of Allium sativum, commonly known as garlic have been consumed in routine foods are known to possess various biological activities. Nevertheless, scientific evidence on the protective effect of SAC against neonatal asthmatic rats is not available. Hence, the present study aimed at investigating the anti-asthmatic activity of SAC in neonatal asthmatic rats using Wistar rats. The study conducted in 4 groups consists of normal control rats, asthma-induced, asthma animals administered with SAC (25 mg/kg), and SAC control. At the end of the experimental period, inflammatory cells in bronchoalveolar lavage fluid (BALF), inflammatory markers, fibrinogen level, activated partial thromboplastin time, coagulation factor activity, and histopathology were elucidated. The current investigation exhibits that SAC significantly reduced the total leukocytes, with restored fibrinogen level, and activated partial thromboplastin time. In addition, the levels of inflammatory cytokines such as TNF-α (tumor necrosis factor- α), IL-6 (Interleukin 6), and IL-1β have also attenuated in SAC treated animals. Furthermore, the mRNA expression levels of COX2 (cyclooxygenase-2), MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated upon activation, normal T cell expressed and secreted), and eotaxin were reduced in SAC treated animals. Treatment of rats with SAC significantly reduced inflammation and eosinophil infiltration in the lungs. These results suggest that SAC exert protection in neonatal asthmatic rats suffering from acute or chronic inflammation by inducing anti-inflammatory and cell-protective responses.

홍산 품종으로 제조한 흑마늘의 이화학적 특성

The present study aimed to confirm the quality characteristics of black garlic aged from ‘Hongsan’ variety developed by the National Institute of Horticultural and Herbal Science and the ‘Namdo’ variety cultivated mainly in Namhae-gun. The total phenolic compounds of aged Hongsan and Namdo garlic increased 1.3- and 1.7-fold, respectively, and total flavonoid contents increased 8.6- and 11.2-flod, respectively. The content of pyruvate and thiosulfinate decreased with aging in both garlic varieties. The S-allyl cysteine (SAC) contents of Hongsan and Namdo garlic were maximal on day 6 and 2 of aging, respectively, before decreasing. The abundance of γ-glutamyl S-allyl cysteine (γ-GSAC) was -2.2-fold higher in fresh Hongsan, than fresh Namdo garlic, and increased to -6-fold after aging. The moisture, pH, acidity, reducing sugar, total sugar, pyruvate, and thiosulfinate contents of aged black garlic did not significantly differ between the two garlic varieties, but the total phenolic compounds and total flavonoids were higher in aged Namdo garlic, whereas hardness, SAC, and γ-GSAC contents were higher in aged Hongsan garlic. The contents of fresh garlic are assumed to be responsible for these difference between the two varieties of aged black garlic.

S-allyl Cysteine, a Garlic Compound, Produces an Antidepressant-Like Effect and Exhibits Antioxidant Properties in Mice.

Depression is a psychiatric disorder, and oxidative stress is a significant mechanism of damage in this mood disorder. It is characterized by an enhancement of oxidative stress markers and low concentrations of endogenous antioxidants, or antioxidants enzymes. This suggests that antioxidants could have an antidepressant effect. S-allyl cysteine (SAC) is a compound with antioxidant action or free radical scavenger capacity. The purpose of the current research was to evaluate the antidepressant-like effect as well as the antioxidant role of SAC on a preclinical test, using the Porsolt forced swim test (FST). SAC (30, 70, 120, or 250 mg/kg, ip) was administered to male BALB/c mice daily for 17 days, followed by the FST at day 18. Oxidative stress markers (reactive oxygen species, superoxide production, lipid peroxidation, and antioxidant enzymes activities) were analyzed in the midbrain, prefrontal cortex, and hippocampus. SAC (120 mg/kg) attenuated the immobility scores (44%) in the FST, and protection was unrelated to changes in locomotor activity. This antidepressant-like effect was related to decreased oxidative stress, as indicated by lipid peroxidation and manganese-superoxide dismutase (Mn-SOD) activity in the hippocampus. SAC exerts an antidepressant-like effect that correlated, in part, with preventing oxidative damage in hippocampus.

Effect of S-allylcysteine against diabetic nephropathy via inhibition of MEK1/2-ERK1/2-RSK2 signalling pathway in streptozotocin-nicotinamide-induced diabetic rats

Objective In the current study, we evaluated the ameliorative effect of S-allylcysteine (SAC) against streptozotocin (STZ)-nicotinamide (NAD)-induced diabetic nephropathy (DN) in rats and also an attempt was made to establish the molecular mechanism of SAC. Methods DN rats were orally supplemented with SAC (150 mg/kg body weight) for a period of 45 days and the effect of SAC on urinary albumin excretion, metabolic parameters, and tubular injury biomarkers by ELISA, total levels and phosphorylation of MEK1/2, ERK1/2, and RSK2 by western blotting analysis in control and experimental rats were assessed. Results From this study, we observed that SAC considerably decreased polydipsia, poly urea, polyphagia, albuminuria and the levels of urinary N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, transforming growth factor-β1 and SAC effectively altered the pathological changes in DN rats. SAC also reserved renal cortical phosphorylation of MEK1/2, ERK1/2 and RSK2. Conclusion Hence this study recommended that SAC can successfully protect the DN through regulation of MEK1/2-ERK1/2-RSK2 signalling.

S-Allylcysteine Protects Against Excitotoxic Damage in Rat Cortical Slices Via Reduction of Oxidative Damage, Activation of Nrf2/ARE Binding, and BDNF Preservation.

Neuroprotective approaches comprising different mechanisms to counteract the noxious effects of excitotoxicity and oxidative stress need validation and detailed characterization. Although S-allylcysteine (SAC) is a natural compound exhibiting a broad spectrum of protective effects characterized by antioxidant, anti-inflammatory, and neuromodulatory actions, the mechanisms underlying its protective role on neuronal cell damage triggered by early excitotoxic insults remain elusive. In this study, we evaluated if the preconditioning or the post-treatment of isolated rat cortical slices with SAC (100μM) can ameliorate the toxic effects induced by the excitotoxic metabolite quinolinic acid (QUIN, 100μM), and whether this protective response involves the early display of specific antioxidant and neuroprotective signals. For this purpose, cell viability/mitochondrial reductive capacity, lipid peroxidation, levels of reduced and oxidized glutathione (GSH and GSSG, respectively), the rate of cell damage, the NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) binding activity, heme oxygenase 1 (HO-1) regulation, extracellular signal-regulated kinase (ERK1/2) phosphorylation, and the levels of tumor necrosis factor-alpha (TNF-α) and the neurotrophin brain-derived neurotrophic factor (BDNF) were all estimated in tissue slices exposed to SAC and/or QUIN. The incubation of slices with QUIN augmented all toxic endpoints, whereas the addition of SAC prevented and/or recovered all toxic effects of QUIN, exhibiting better results when administered 60min before the toxin and demonstrating protective and antioxidant properties. The early stimulation of Nrf2/ARE binding activity, the upregulation of HO-1, the ERK1/2 phosphorylation and the preservation of BDNF tissue levels by SAC demonstrate that this molecule displays a wide range of early protective signals by triggering orchestrated antioxidant responses and neuroprotective strategies. The relevance of the characterization of these mechanisms lies in the confirmation that the protective potential exerted by SAC begins at the early stages of excitotoxicity and neurodegeneration and supports the design of integral prophylactic/therapeutic strategies to reduce the deleterious effects observed in neurodegenerative disorders with inherent excitotoxic events.

Elucidation of S-Allylcysteine Role in Inducing Apoptosis by Inhibiting PD-L1 Expression in Human Lung Cancer Cells.

The aim of this study is to explore the therapeutic potential of S-allylcysteine (SAC) organosulphur compound as a potent immune checkpoint inhibitor PD-L1. Natural compounds have been showing tremendous anticancerous potential via suppressing the expression of genes involved in the development and progression of several carcinomas. This has further motivated us to explore the therapeutic potential of organosulphur compounds as potent immune checkpoint inhibitors. Our study was designed to elucidate the potential of S-allylcysteine (SAC) as significant PD-L1 (immune checkpoint) inhibitor in human lung cancer A549 cancer cell line by using both the in vitro and in silico approaches. Anticancerous effect of the SAC on lung cancer cells was determined by using the MTT cell viability. Apoptotic induction was confirmed by Hoechst staining, percent caspase-3 activity as well as gene expression analysis by real time PCR. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Additionally, ligand-target protein interaction was analysed by molecular docking. Cell growth and proliferation was significantly reduced in SAC treated A549 cells in a concentration and time.dependent manner. The effect of SAC on apoptotic induction was analyzed by enhanced nuclear condensation, increased percent caspase-3 activity as well as modulation of apoptotic genes. Furthermore, SAC treatment also resulted in reduced expression of PD-L1 and HIF-1α. Additionally, in silico analysis also supported the in vitro findings by showing efficient docking with PD-L1 immune checkpoint target. Therefore, our results clearly suggested that SAC could serve as a novel chemotherapeutic candidate for the treatment of lung cancer by inhibiting immune checkpoint target PD-L1 in human lung cancer cells. Additionally, our study also explained a novel molecular mechanism of its antitumor activity.

S-allyl cysteine: A potential compound against skeletal muscle atrophy

BackgroundOxidative stress is crucial player in skeletal muscle atrophy pathogenesis. S-allyl cysteine (SAC), an organosulfur compound of Allium sativum, possesses broad-spectrum properties including immuno- and redox-modulatory impact. Considering the role of SAC in regulating redox balance, we hypothesize that SAC may have a protective role in oxidative-stress induced atrophy. MethodsC2C12 myotubes were treated with H2O2 (100 μM) in the presence or absence of SAC (200 μM) to study morphology, redox status, inflammatory cytokines and proteolytic systems using fluorescence microscopy, biochemical analysis, real-time PCR and immunoblotting approaches. The anti-atrophic potential of SAC was confirmed in denervation-induced atrophy model. ResultsSAC pre-incubation (4 h) could protect the myotube morphology (i.e. length/diameter/fusion index) from atrophic effects of H2O2. Lower levels of ROS, lipid peroxidation, oxidized glutathione and altered antioxidant enzymes were observed in H2O2-exposed cells upon pre-treatment with SAC. SAC supplementation also suppressed the rise in cytokines levels (TWEAK/IL6/myostatin) caused by H2O2. SAC treatment also moderated the degradation of muscle-specific proteins (MHCf) in the H2O2-treated myotubes supported by lower induction of diverse proteolytic systems (i.e. cathepsin, calpain, ubiquitin-proteasome E3-ligases, caspase-3, autophagy). Denervation-induced atrophy in mice illustrates that SAC administration alleviates the negative effects (i.e. mass loss, decreased cross-sectional area, up-regulation of proteolytic systems, and degradation of total/specific protein) of denervation on muscles. ConclusionsSAC exerts significant anti-atrophic effects to protect myotubes from H2O2-induced protein loss and myofibers from denervation-induced muscle loss, due to the prevention of elevated proteolytic systems and inflammatory/oxidative molecules. General significanceThe results signify the potential of SAC against muscle atrophy.

S‑1‑Propenylcysteine, a sulfur compound in aged garlic extract, alleviates cold‑induced reduction in peripheral blood flow in rat via activation of the AMPK/eNOS/NO pathway

Aged garlic extract (AGE) has been shown to improve peripheral circulatory disturbances in both clinical trials and experimental animal models. To investigate the effect of S-1-propenylcysteine (S1PC), a characteristic sulfur compound in AGE, on cold-induced reduction in tail blood flow of rat, Wistar rats were individually placed in a restraint cage and given the treatment with cold water (15˚C) after the oral administration of AGE or its constituents S1PC, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC). After the cold-treatment the tail blood flow of rats was measured at the indicated times. The pretreatment with AGE (2 g/kg BW) and S1PC (6.5 mg/kg BW) significantly alleviated the reduction of rat tail blood flow induced by cold treatment. The effect of S1PC was dose-dependent and maximal at the dose of 6.5 mg/kg BW, whereas SAC and SAMC were ineffective. To gain insight into the mechanism of S1PC action, the concentration of nitrogen oxide metabolites (NOx) in the plasma and the levels of phosphorylated endothelial nitric oxide synthase (eNOS) and 5'-AMP-activated protein kinase (AMPK) in the aorta were measured. The pretreatment with S1PC significantly increased the plasma concentration of NOx as well as the level of phosphorylated form of AMPK and eNOS in the aorta after cold-treatment. The present findings suggest that S1PC is a major constituent responsible for the effect of AGE to alleviate the cold-induced reduction of peripheral blood flow in rat by acting on the AMPK/eNOS/NO pathway in the aorta.

Administration of S-allyl cysteine to neonatal rats modulates inflammatory biomarkers in high-fructose-fed rats in adulthood

Purpose: To investigate the potential prophylactic effect of S-allyl cysteine (SAC), found in garlic (Allium sativum), against the development of apro-inflammatory status induced by diet in neonatal rats later on in adulthood.Methods: Suckling Wistar rat pups (4-day-old; male = 21 and female = 21) were randomly allocated to either of 3 groups and orally gavaged daily with the following treatments from postnatal day (PND) 6– 20: group 1 (control) - 10 mL/kg distilled water; group 2 - 10 mL/kg of 20 % w/v fructose solution (FS) and group 3 - 10 mL/kg FS + SAC. The rat pups were weaned on PND 21, and given ad libitum access to standard rat chow and plain drinking up to PND 115. The rats were euthanized on PND 116 and plasma was collected for the determination of interleukins (IL-1β, IL-4, IL-5, IL-10), vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1)] using Bio-Plex Pro magnetic beadbased assays on Bio-Plex platform.Results: Oral administration of FS during suckling increased significantly (p < 0.05) plasma concentrations of IL-5, MCP-1 and VEGF in adult male rats, and plasma MCP-1 in adult female rats. Neonatal oral administration of SAC prevented FS-programmed increase in pro-inflammatory cytokines(p < 0.05) later on in adulthood.Conclusion: Oral administration of SAC during the neonatal period protected against FS-induced proinflammatory status and thus, could possibly be exploited as a prophylactic or intervention agent againsta pro-inflammatory status induced by a high fructose diet.
 Keywords: S-Allyl cysteine, Fructose solution, Cytokines, Pro-inflammatory chemokines, Neonatal programming

Improvement of Learning and Memory in Senescence-Accelerated Mice by S-Allylcysteine in Mature Garlic Extract.

S-allylcysteine (SAC), a major thioallyl compound contained in mature garlic extract (MGE), is known to be a neuroactive compound. This study was designed to investigate the effects of SAC on primary cultured hippocampal neurons and cognitively impaired senescence-accelerated mice prone 10 (SAMP10). Treatment of these neurons with MGE or SAC significantly increased the total neurite length and number of dendrites. SAMP10 mice fed MGE or SAC showed a significant improvement in memory dysfunction in pharmacological behavioral analyses. The decrease of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-d-aspartate (NMDA) receptor, and phosphorylated α-calcium/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal tissue of SAMP10 mice fed MGE or SAC was significantly suppressed, especially in the MGE-fed group. These findings suggest that SAC positively contributes to learning and memory formation, having a beneficial effect on brain function. In addition, multiple components (aside from SAC) contained in MGE could be useful for improving cognitive function by acting as neurotrophic factors.

Thallium Toxicity in Caenorhabditis elegans: Involvement of the SKN-1 Pathway and Protection by S-Allylcysteine.

Monovalent thallium (Tl+) is a cation that can exert complex neurotoxic patterns in the brain by mechanisms that have yet to be completely characterized. To learn more about Tl+ toxicity, it is necessary to investigate its major effects in vivo and its ability to trigger specific signaling pathways (such as the antioxidant SKN-1 pathway) in different biological models. Caenorhabditis elegans (C. elegans) is a nematode constituting a simple in vivo biological model with a well-characterized nervous system, and high genetic homology to mammalian systems. In this study, both wild-type (N2) and skn-1 knockout (KO) mutant C. elegans strains subjected to acute and chronic exposures to Tl+ [2.5-35μM] were evaluated for physiological stress (survival, longevity, and worm size), motor alterations (body bends), and biochemical changes (glutathione S-transferase regulation in a gst-4 fluorescence strain). While survival was affected by Tl+ in N2 and skn-1 KO (worms lacking the orthologue of mammalian Nrf2) strains in a similar manner, the longevity was more prominently decreased in the skn-1 KO strain compared with the wild-type strain. Moreover, chronic exposure led to a greater compromise in the longevity in both strains compared with acute exposure. Tl+ also induced motor alterations in both skn-1 KO and wild-type strains, as well as changes in worm size in wild-type worms. In addition, preconditioning nematodes with the well-known antioxidant S-allylcysteine (SAC) reversed the Tl+-induced decrease in survival in the N2 strain. GST fluorescent expression was also decreased by the metal in the nematode, and recovered by SAC. Our results describe and validate, for the first time, features of the toxic pattern induced by Tl+ in an in vivo biological model established with C. elegans, supporting an altered redox component in Tl+ toxicity, as previously described in mammal models. We demonstrate that the presence of the orthologous SKN-1 pathway is required for worms in evoking an efficient antioxidant defense. Therefore, the nematode represents an optimal model to reproduce mammalian Tl+ toxicity, where toxic mechanisms and novel therapeutic approaches of clinical value may be successfully pursued.

S-allyl cysteine, an active ingredient of garlic, attenuates acute liver dysfunction induced by lipopolysaccharide/ d-galactosamine in mouse: Underlying mechanisms.

In the present study, beneficial effect of S-allyl cysteine (SAC) was evaluated in the lipopolysaccharide/d-galactosamine (LPS/d-Gal) model of acute liver injury (ALI). To mimic ALI, LPS and d-Gal (50 μg/kg and 400 mg/kg, respectively) were intraperitoneally administered and animals received SAC per os (25 or 100 mg/kg/d) for 3 days till 1 hour before LPS/d-Gal injection. Pretreatment of LPS/d-Gal group with SAC-lowered activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and partially reversed inappropriate alterations of hepatic oxidative stress- and inflammation-related biomarkers including liver reactive oxygen species, malondialdehyde, and hepatic activity of the defensive enzyme superoxide dismutase, ferric reducing antioxidant power (FRAP), toll-like receptor-4 (TLR4), cyclooxygenase 2, NLR family pyrin domain containing 3 (NLRP3), caspase 1, nuclear factor κB (NF-κB), interleukin 1β (IL-1β), IL-6, tumor necrosis factor-α, and myeloperoxidase activity. Additionally, SAC was capable to ameliorate apoptotic biomarkers including caspase 3 and DNA fragmentation. In summary, SAC can protect liver against LPS/d-Gal by attenuation of neutrophil infiltration, oxidative stress, inflammation, apoptosis, and pyroptosis which is partly linked to its suppression of TLR4/NF-κB/NLRP3 signaling.

2-Vinyl-4H-1,3-Dithiin, a Bioavailable Compound from Garlic, Inhibits Vascular Smooth Muscle Cells Proliferation and Migration by Reducing Oxidative Stress.

Organosulfur compounds (OSCs) of garlic have various health benefits including anti-hypertensive effect. It has been described that volatile OSCs uptake occurs into a moderate extent. Among the bioavailable OSCs present in garlic, 2-vinyl-4H-1,3-dithiin (2VD) is a main component in garlic macerated oil and stir-fried garlic but has been poorly investigated compared with others OSCs, such allyl mercaptan (AM) and S-allyl cysteine (SAC). The aim of this study was to evaluate the effects of 2VD on vascular smooth muscle cells (VSMCs) isolated from spontaneous hypertensive rats (SHR) and compare them with those produced by AM and SAC. Cell viability and proliferation were measured using tetrazolium dye MTT assay and flow cytometry. Cell migration was evaluated by scrape-wound migration assay. OSCs anti-oxidative capacity was determined by measuring reactive oxygen species (ROS) generation, and total antioxidant status (TAS). Non-toxic plasmatic concentrations (10μgL-1) of 2VD and AM inhibited VSMCs proliferation stimulated with 5% fetal bovine serum and impaired cell migration. In further flow cytometry analysis 2VD treatment resulted in a partial cell cycle arrest at G2 phase. The OSCs tested were able to prevent ROS increase after angiotensin II stimulation and surprisingly 2VD induced higher total antioxidant status compared with AM and SAC. Our results showed that 2VD produces equivalent or superior beneficial effects on VSMCs to those reported for other bioavailable compounds of garlic. This preliminary evidence suggests that 2VD intake could also exert important protective effects against arterial remodeling in hypertension.

S-allyl cysteine protects retinal pigment epithelium cells from hydroquinone-induced apoptosis through mitigating cellular response to oxidative stress.

Retinal pigment epithelium (RPE) degenerative death is an evident hallmark of advanced age-related macular degeneration (AMD). The present study aims to evaluate the protective effects of S-allyl L-cysteine (SAC), a bioactive component from aged garlic extracts, on the oxidative stress-related apoptosis of RPE cells and to investigate the potential underlying mechanisms. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were performed to evaluate the effects of SAC on the hydroquinone-treated human ARPE19 cells. The Reactive Oxygen Species (ROS) production was measured by virtue of flow cytometry or determined under an inverted fluorescence microscope. Furthermore, the expression of antioxidant factor Nrf2, as well as downstream antioxidant genes, including NQO1, SOD1, SOD2, and HO1 was assessed in hydroquinone stimulated ARPE19 cells, in the presence or absence of SAC pretreatment. Hydroquinone incitement contributed to a marked decrease in cell viability, but enhanced cell apoptosis, whereas SAC addition did not cause significant alterations. When cells were pre-treated with SAC, cell proliferation was dramatically enhanced whereas apoptosis was mitigated, and the ROS generation induced by hydroquinone was also significantly suppressed, indicating a prominent function of SAC in preventing ARPE19 cells from oxidant-related apoptosis. The elevated expression levels of Nrf2 and other antioxidant genes driven by hydroquinone were downregulated by SAC addition. These data suggest that SAC can effectively attenuate hydroquinone-induced oxidative damage in human RPE cells. Our work is the first to demonstrate that SAC modulates oxidative stress-induced RPE apoptosis, thereby potentially proving new insights into the treatment of AMD.

Optimisation of the Method of Stem Cells Mediated Tissue Remodelling in Diabetic Wound Healing

Introduction: Incomplete, slow or limited wound healing is one of the major disabling events accompanying diabetic patients. At the present time, there is no effective treatments which enable efficient wound healing in diabetic patients. Aim: To optimise the method of loading of Human Mesenchymal Stem Cells (MSC) with S-Allyl Cysteine (SAC) from aged garlic extract and invitro optimisation of the delivery process, attachment and optimisation of stem cells and loaded stem cells to the fibroin matrix in induction of wound recovery completion in a model of diabetic wound healing. Materials and Methods: It was a preclinical invitro model which employed the anti-inflammatory and anti-bacterial properties of fibroin matrix after populating them with drug-loaded human MSCs. This combination allowed slow and sustained release of the active substance into the wound and with the stem cells, promoted tissue remodelling thereby, inducing enhanced wound recovery in diabetic model. Results: Mixture of SAC and N-Acetylcysteine (NAC) was most effective. S-Allyl Mercaptocysteine (SAMC) protected angiogenesis and showed tube formation in the presence of advanced glycation end-products. Protection against oxidative stress and apoptosis-Propidium Iodide (PI) staining shows protective effects of the cysteine compounds particularly SAC and SAMC. Conclusion: Present study results provide possibilities of utilising tissue-engineered fibroin matrix with drug loaded human MSC as a potential therapeutic technique, due to its beneficial effects in terms of cell attachment and bioactive factor loading, for diabetic wound healing.

Antimicrobial Activity of Garlic Derivatives on Common Causative Microorganisms of the External Ear Canal and Chronic Middle Ear Infections.

Today, antibiotic resistance is increasing and evolving into an important health problem. Therefore, it is important to research on alternative therapies to antibiotics. This study aimed to investigate the inhibitory effect of four garlic derivatives on microorganisms commonly isolated in ear infections. The antimicrobial activities of allicin, s-allyl cysteine (SAC), diallyl disulfide (DADS), and s-allyl mercaptocysteine (SAMC) were investigated on standard strains of commonly isolated microorganisms using the broth microdilution method. The test strains were selected among the microorganisms responsible for chronic suppurative otitis media and otitis externa. These microorganisms were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium, Candida albicans, and Candida tropicalis. Minimum inhibitory concentration (MIC) values of allicin and SAC ranged from 0.125 to 20 μg/mL for fermentative bacteria (E. coli and K. pneumoniae), 20 to 80 μg/mL for non-fermentative bacteria (P. aeruginosa and A. baumannii), 5 to 10 μg/mL for gram-positive cocci (S. aureus and E. faecium), and 40 to 80 μg/mL for yeasts (C. albicans and C. tropicalis). MIC values of DADS ranged from 40 to 80 μg/mL for fermentative bacteria, 40 to 160 μg/mL for non-fermentative bacteria, 40 to 80 μg/mL for gram-positive cocci, and 20 to 40 μg/mL for yeasts. The MICs of SAMC were >640 μg/mL for the tested bacteria and yeasts. Both allicin and SAC showed antimicrobial activity against the tested microorganisms, even at low concentrations. These two derivatives may be used to treat infections in the future.

A Review of Component and Pharmacology Activities of Black Garlic

Black garlic is garlic fermented in high temperature and humidity, and the fermentation compound chemical in garlic changes to new chemicals, such as S-allyl cysteine (SAC), S-allylmercapto-cysteine, and arginine. The color changed to dark brown during the aging period because of the Maillard reaction, known as non-enzymatic browning reaction. Black garlic has 57.14% of fructose, 6.78% of glucose, and 7.62% of sucrose, which were mainly saccharides in black garlic to answer for its sweet taste. It is such a pharmacological activity which contains antioxidant, anti-cancer, hepatoprotective, can improve the immune system, reduce hyperglycemia, dyslipidemia, and anti-allergic. We summarize the current knowledge of a change in the components, bioactivity, production, and applications of black garlic, as well as the proposed future prospects on their possible applications as a functional pharmacy product.

Sulfur-containing amino acids in aged garlic extract inhibit inflammation in human gingival epithelial cells by suppressing intercellular adhesion molecule-1 expression and IL-6 secretion.

Aged garlic extract (AGE) contains various biologically active sulfur-containing amino acids, such as S-allylcysteine (SAC), S-1-propenylcysteine (S1PC) and S-allylmercaptocysteine (SAMC). These amino acids have been demonstrated to lower hypertension, improve atherosclerosis and enhance immunity through their anti-inflammatory and antioxidant activities. It was recently reported that the administration of AGE alleviated gingivitis in a clinical trial. In this study, to gain insight into this effect of AGE, the authors examined whether AGE and the three above-mentioned sulfur compounds influence the effects of tumor necrosis factor-α (TNF-α) in inducing intercellular adhesion molecule-1 (ICAM-1) expression and interleukin-6 (IL-6) secretion in Ca9-22 human gingival epithelial cells. It was found that S1PC reduced the level of ICAM-1 protein induced by TNF-α possibly through post-translational levels without affecting the TNF-α-induced mRNA expression. However, SAC and SAMC had no effect. It was also confirmed the inhibitory effect of an antimicrobial peptide [human-β defensin-3 (hβD3)] and found that the inhibitory effects of hbD3 and S1PC were synergistic. On the other hand, the TNF-α-induced IL-6 secretion was attenuated by SAC and SAMC in a dose-dependent manner, whereas S1PC was ineffective. In addition, SAC and SAMC, but not S1PC inhibited the phosphorylation of the transcription factor nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), which is involved in the expression of inflammatory molecules, suggesting that the anti-inflammatory effects of SAC and SAMC are mediated, at least partly, by NF-κB. On the whole, the findings of this study suggest that the three sulfur amino acids in AGE function synergistically in alleviating inflammation in human gingival epithelial cells.