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Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia and impaired islet secretion that places a heavy burden on the global health care system due to its high incidence rate, long disease course and many complications. Fortunately, garlic (Allium sativum L.), a well-known medicinal plant and functional food without the toxicity and side effects of conventional drugs, has shown positive effects in the treatment of diabetes and its complications. With interdisciplinary development and in-depth exploration, we offer a clear and comprehensive summary of the research from the past ten years, focusing on the mechanisms and development processes of garlic in the treatment of diabetes and its complications, aiming to provide a new perspective for the treatment of diabetes and promote the efficient development of this field. [ABSTRACT FROM AUTHOR]

Purpose: Renal failure is an end-stage consequence after persistent hyperglycemia during diabetic nephropathy (DN), and the etiology of DN has been linked to oxidative stress. The purpose of this research was to determine the beneficial synergistic effects of S-Allyl Cysteine (SAC) and Taurine (TAU) on oxidative damage in the kidneys of type 2 diabetic rats induced by hyperglycemia. Design/methodology/approach: Experimental diabetes was developed by administering intraperitoneal single dose of streptozotocin (STZ; 65 mg/kg) with nicotinamide (NA; 230 mg/kg) in adult rats. Diabetic and control rats were treated with SAC (150 mg/kg), TAU (200 mg/kg) or SAC and TAU combination (75 + 100 mg/kg) for four weeks. The estimation of body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), oxidative stress markers along with kidney histopathology was done to investigate the antidiabetic potential of SAC/TAU in the NA/STZ diabetic group. Findings: The following results were obtained for the therapeutic efficacy of SAC/TAU: decrease in blood glucose level, decreased level of thiobarbituric acid reactive substances (TBARS) and increased levels of GSH, glutathione-s-transferase (GST) and catalase (CAT). SAC/TAU significantly modulated diabetes-induced histological changes in the kidney of rats. Originality/value: SAC/TAU combination therapy modulated the oxidative stress markers in the kidney in diabetic rat model and also prevented oxidative damage as observed through histopathological findings. [ABSTRACT FROM AUTHOR]

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs (S-Allyl Cysteine Poly (D,L-lactide-co-glycolic acid) Nanoparticles) were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency to be 5.13 ± 0.10% and 82.36 ± 4.01%, respectively. SC PLGA NPs showed a spherical morphology of an average size (134.8 ± 4.61 nm), PDI: 0.277 ± 0.004, and −25.3 ± 1.03 mV Zeta-Potential (ZP), and is suitable for oral delivery. The development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameter examinations with 1.219 min RT, MS (162.00/73.10), and a total run-time of 2.0 min. Additionally, 1.0–1000.0 ng/mL was a linear range with inter- and intra-day accuracy of 92.55–99.40%, followed by a precision of 1.88–4.23%. SC PLGA NP's oral bioavailability was significantly higher (** p < 0.01) in comparison to the SC-S treated groups' (iv and oral). The antimicrobial activity of SC PLGA NPs proved to be more effective than pure S-Allyl-L-Cysteine with significant results (p < 0.01) in comparison to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties, which can be helpful for oral administration. Based on the proposed research results, SC PLGA NPs were used for the improvement in oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery. [ABSTRACT FROM AUTHOR]

The objective of this review focus on black garlic (BG) extract structural composition, and functional foods reduce the risk of developing disease rather than prevent or have pharmacology action. The different groups of health-promoting phytoconstituents such as total phenolics, S-allyl cysteine, hydroxycinnamic acid derivatives are present 5-(hydroxymethyl)furfural and its strong antioxidant components were present in BG, compared with raw garlic. This review demonstrated various ameliorative properties of BG with molecular mechanisms, regulation of lipid metabolism, free radical scavenging, anti-lipid peroxidation, alleviation of insulin resistance, and reducing blood glucose as well as pharmacological applications in animals and cell lines. Further, the recent scientific advances about therapeutic and industrial applications of BG are summarized. This review summarizes and discusses up-dated information on molecular mechanisms underlying and biological activities of BG with potential applications in the treatment of chronic diseases for improving human health. [ABSTRACT FROM AUTHOR]

Abstract The present study was designed to evaluate the beneficial synergistic effects of S-allyl Cysteine (SAC) and Taurine (TAU) on hyperglycemia, lipid profile and renal damage markers in type 2 diabetes mellitus (T2DM) in rats. Experimental T2DM was developed by administering an intraperitoneal single dose of nicotinamide (NA; 230 mg/kg) and streptozotocin (STZ; 65 mg/ kg) in adult rats. Control and diabetic rats were treated with SAC (150 mg/kg); TAU (200 mg/ kg) or SAC and TAU (75+100 mg/kg) combination for four weeks. Measurements of traditional markers of kidney toxicity in serum, such as blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), together with serum cholesterol/triglyceride such as serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) may yield a snapshot of renal damage and lipid profile in NA/STZ-treated rats. The variation in levels of fasting blood glucose, glycosylated hemoglobin, insulin and lipid profile was significantly augmented in SAC/TAU treatment group. The diabetic group showed elevated renal injury markers in serum, which were decreased significantly by SAC/TAU treatment. Thus the results of the experiment clearly indicate the potential of the SAC/TAU combination in improving diabetic complications.

In recent years, derivatives of natural compounds are synthesized to increase the bioavailability, pharmacology, and pharmacokinetics properties. The naphthoquinone, plumbagin (PLU), is well known for its anticancer activity. However, the clinical use of PLU is hindered due to its toxicity. Previous reports have shown that modification of PLU at 5ʹ-hydroxyl group has reduced its toxicity towards normal cell line. In accordance, in the present study, 5ʹ-hydroxyl group of PLU was esterified with S-allyl cysteine (SAC) to obtain PLU-SAC ester. The drug-likeness of PLU-SAC was understood by in silico ADME analysis. PLU-SAC was characterized by UV–visible spectroscopy, mass spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Molecular docking and dynamics simulation analysis revealed the interaction of PLU-SAC with proteins of interest in cancer therapy such as human estrogen receptor α, tumor protein p53 negative regulator mouse double minute 2, and cyclin-dependent kinase 2. MMGBSA calculation showed the favorable binding energy which in turn demonstrated the stable binding of PLU-SAC with these proteins. PLU-SAC showed apoptosis in breast cancer cell line (MCF-7) by inducing oxidative stress, disturbing mitochondrial function, arresting cells at G1 phase of cell cycle, and initiating DNA fragmentation. However, PLU-SAC did not show toxicity towards normal Vero cell line. PLU-SAC was synthesized and structurally characterized, and its anticancer activity was determined by in silico and in vitro analysis. [ABSTRACT FROM AUTHOR]

Therapeutic approaches based on isolated compounds derived from natural products are more common in preventing diseases involving inflammation and oxidative stress at present. S-allyl cysteine (SAC) is a promising garlic-derived organosulfur compound with many positive effects in cell models and living systems. SAC has biological activity in various fields, enclosing healing in learning and memory disorders, neurotrophic effects, and antioxidant activity. In this study, we purposed to identify the neuroprotective activity of SAC toward 6-OHDA-induced cell demise in the SH-SY5Ycell line. For this purpose, 6-OHDA-induced cytotoxicity, and biochemical, and gene expression changes were evaluated in SH-SY5Y cells. SH-SY5Y cells grown in cell culture were treated with SAC 24 h before and after 6-OHDA application. Then, cell viability, antioxidant parameters, and gene expressions were measured. Finally, immunofluorescence staining analysis was performed. Our results showed that SAC increased cell viability by 144 % at 80 µg/mL with pre-incubation (2 h). It was observed that antioxidant levels were significantly increased and oxidative stress marker levels were decreased in cells exposed to 6-OHDA after pre-treatment with SAC ( p<0.05 ). SAC supplementation also suppressed the increase in pro-inflammation levels (TNF-α/IL1/IL8) caused by 6-OHDA (p < 0.05). While 8-OHdG and Nop10 expressions were observed at a mild level in SAC pretreatment depending on the dose, 8-OHdG, and Nop10 expressions were observed at a moderate level in SAC treatment after 6-OHDA application (p<0.05) . Our findings demonstrate the positive effect of pretreatment with SAC on SH-SY5Y cells injured by 6-OHDA, suggesting that SAC may be beneficial for neuroprotection in regulating oxidative stress and neuronal survival in an in vitro model of Parkinson's disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Abstract In order to overcome the challenges of discovering new antiprotozoal drugs, we synthesized a new class of hybrids based on S-allylCysteine Ester/Caffeic Acid Amide and evaluated four of them against Trypanosoma cruzi and Plasmodium falciparum. Hybrid 6 exhibited good activity on T. cruzi with an EC50 value of 5.45 µM, whereas hybrid 3 was active over P. falciparum with an EC50 of 18.08 µM. All hybrids displayed a good selectivity index on P. falciparum. Molecular docking computations indicated that several hybrids have good binding affinities towards the protozoa related enzymes (Cruzipain or Falcipain-2) when compared against current inhibitors. In silico studies showed that conjugates 1-3 and 6 fulfilled optimal ADME characteristics, suggesting them as safe alternatives for oral treatment of protozoal infections.

A newly UHPLC-MS/MS method development and validation for S-Allyl Cysteine was used to evaluate the comparative pharmacokinetic parameters. SC PLGA NPs (S-Allyl Cysteine Poly (D,L-lactide-co-glycolic acid) Nanoparticles) were developed by the emulsion solvent evaporation method. SC PLGA NPs showed their drug loading and encapsulation efficiency to be 5.13 ± 0.10% and 82.36 ± 4.01%, respectively. SC PLGA NPs showed a spherical morphology of an average size (134.8 ± 4.61 nm), PDI: 0.277 ± 0.004, and −25.3 ± 1.03 mV Zeta-Potential (ZP), and is suitable for oral delivery. The development and validation of the UHPLC-MS/MS bioanalytical method were performed successfully for PK-parameter examinations with 1.219 min RT, MS (162.00/73.10), and a total run-time of 2.0 min. Additionally, 1.0–1000.0 ng/mL was a linear range with inter- and intra-day accuracy of 92.55–99.40%, followed by a precision of 1.88–4.23%. SC PLGA NP’s oral bioavailability was significantly higher (** p < 0.01) in comparison to the SC-S treated groups’ (iv and oral). The antimicrobial activity of SC PLGA NPs proved to be more effective than pure S-Allyl-L-Cysteine with significant results (p < 0.01) in comparison to SC-S. SC PLGA NPs showed fitted physicochemical and enhanced antimicrobial properties, which can be helpful for oral administration. Based on the proposed research results, SC PLGA NPs were used for the improvement in oral bioavailability with a sustained and controlled release of S-Allyl-L-Cysteine delivery.

S‐allyl cysteine (SAC), which is the most abundant bioactive compound in black garlic (BG; Allium sativum), has been shown to have antioxidant, anti‐apoptotic, anti‐inflammatory, anti‐obesity, cardioprotective, neuroprotective, and hepatoprotective activities. Sulfur compounds are the most distinctive bioactive elements in garlic. Previous studies have provided evidence that the concentration of SAC in fresh garlic is in the range of 19.0–1736.3 μg/g. Meanwhile, for processed garlic, such as frozen and thawed garlic, pickled garlic, fermented garlic extract, and BG, the SAC content increased to up to 8021.2 μg/g. BG is an SAC‐containing product, with heat treatment being used in nearly all methods of BG production. Therefore, strategies to increase the SAC level in garlic are of great interest; however, further knowledge is required about the effect of processing factors and mechanistic changes. This review explains the formation of SAC in garlic, introduces its biological effects, and summarizes the recent advances in processing methods that can affect SAC levels in garlic, including heat treatment, enzymatic treatment, freezing, fermentation, ultrasonic treatment, and high hydrostatic pressure. Thus, the aim of this review was to summarize the outcomes of treatment aimed at maintaining or increasing SAC levels in BG. Therefore, publications from scientific databases in this field of study were examined. The effects of processing methods on SAC compounds were evaluated on the basis of the SAC content. This review provides information on the processing approaches that can assist food manufacturers in the development of value‐added garlic products. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the protective effect of S-allyl cysteine (SAC) against cerebral ischemia reperfusion injury (CRI) in rats. Methods: The protective effect of SAC was determined in a male Wistar rat model of middle cerebral artery occlusion (MCAO)-stimulated transient focal ischemia, followed by reperfusion. Cerebral ischemia reperfusion injury was induced via 90 min of MCAO, followed by 24-h reperfusion. The cerebral infarct size was determined by staining with 2,3,5- triphenyl tetrazolium chloride. The onset of cellular derangement, neurological deficit score and neuronal oedema were determined. In addition, the expressions of CRI markers and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Results: Rats subjected to CRI showed marked increases in cellular oxidative stress, as evidenced by significant increase in the levels of inflammatory markers, including MDA (p < 0.05), MPO (p < 0.05) and nitric oxide (p < 0.01). In addition, CRI increased the mRNA expression levels of the marker genes TLR4, syndecan-1, CSF, aquaporin-1, OCT3, and RFX1. In contrast, rats pre-treated with SAC prior to CRI displayed reduced levels of inflammatory cytokines, with a near-normal cellular arrangement. SAC treatment significantly reduced the mRNA expression levels of the marker genes in CRI rats. Conclusion: These findings suggest that SAC may protect the brain of rats from cerebral ischemiareperfusion injury caused by amplification of oxidative stress and inflammatory signaling. Thus, S-allyl cysteine is a potential therapy for the management of CRI. [ABSTRACT FROM AUTHOR]

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.

The present study was conducted to determine whether black garlic (BG) which is aged by pectinase treatment with high hydrostatic pressure processing has the protective effects in experimental model of acute reflux esophagitis (RE). BG was orally administered at a dose of 100 mg/kg body weight 2 h prior to induction of RE, and the effects were compared with those of raw garlic (RG). Esophageal pathological changes were analyzed using gross and histological examinations. The anti-oxidant and inflammatory protein levels were determined using western blotting. Moreover, RE-induced histological change was markedly suppressed by BG rather than RG. The reduced catalase was increased significantly by BG supplementation; however, superoxide dismutase levels showed a tendency to increase in the esophagus. Overall, the ameliorative effects of BG were superior to those when RG. These data reveal that that BG treatment ameliorates the development of esophagitis via regulation of NF-κB mediated inflammation.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed at late stages, when the tumor has disseminated to other organs. Moreover, it is common to observe that malignant cells may acquire resistance to conventional chemotherapies through different mechanisms, including reducing drug activation or accumulation (by enhancing efflux), inducing alterations in molecular targets, and inhibiting the DNA damage response, among other strategies. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) that exhibited selective cytotoxicity against SW480 cells, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated the possible mechanisms of these molecules in greater depth, to identify whether they could be valuable therapeutic scaffolds in the search for new molecules with chemopreventive potential for the treatment of CRC. Both compounds reduced ROS formation, which could be related to antioxidant effects. Further evaluations showed that SAC-CAFA-MET induces cell death independent of caspases and the tumor-suppressor protein p53, but probably mediated by the negative regulation of the pro-apoptotic Bcl-2. In addition, the lack of activation of caspase-8 and the positive regulation of caspase-3 induced by SAC-CAFA-PENT suggest that this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathways. Furthermore, the downregulation of IL-6 by SAC-CAFA-PENT suggests that it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which SAC-CAFA-PENT elicits apoptosis in SW480human colorectal adenocarcinoma cells. Meanwhile, density functional theory (DFT) calculations suggest that both hybrids would produce effects in the modulation of ROS in SW480 cells via the hydrogen atom transfer (HAT) pathway. The present work notes that SAC-CAFA-MET and SAC-CAFA-PENT could be potential candidates for further investigations in the search for potential chemopreventive agents.

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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.

S-allyl cysteine (SAC), has shown itself to performance important activity as a neuroprotective agent. This action is prompted by antioxidative activity. The aim of this study was to evaluate the neuroprotective effect of SAC, the principal organosulfur compound of garlic, on experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS). Young-adult Dark Agouti rats were used. The experimental model of EAE was carried out by means of mielyn oligodendrocyte glycoprotein (MOG). The effects of MOG were evaluated by changes in: clinical score, biomarkers of oxidative/nitrosative stress, antioxidants, mitochondrial viability and neurohistologic viability. Our results reveal that MOG causes oxidative/nitrosative damage in brain and spinal cord, a decrease in the glutathione redox system and cell loss, whereas SAC administration attenuates the effects of MOG. In addition, SAC was the most effective treatment used in this study. The data show the ability of SAC to modify the development of EAE.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 bead-based 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 against a pro-inflammatory status induced by a high fructose diet. [ABSTRACT FROM AUTHOR]

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer’s disease (AD) is one of the most complicated neurodegenerative diseases causing dementia in human beings. Aside from that, the incidence of AD is increasing and its treatment is very complicated. There are several known hypotheses regarding the pathology of Alzheimer’s disease, including the amyloid beta hypothesis, tau hypothesis, inflammation hypothesis, and cholinergic hypothesis, which are investigated in different research to completely elucidate the pathology of AD. Besides, some new mechanisms, such as immune, endocrine, and vagus pathways, as well as bacteria metabolite secretions, are being explained as other causes to be somehow related to AD pathogenesis. There is still no definite treatment for Alzheimer’s disease that can completely cure and eradicate AD. Garlic (Allium sativum) is a traditional herb used as a spice in different cultures, and due to the organosulfur compounds, like allicin, it possesses highly anti-oxidant properties. Methods and Materials: the benefits of garlic in cardiovascular diseases, like hypertension and atherosclerosis, have been examined and reviewed, although its beneficiary effects in neurodegenerative diseases, such as AD, are not completely understood. In this review, we discuss the effects of garlic based on its components, such as allicin and S-allyl cysteine, on Alzheimer’s disease and the mechanisms of garlic components that can be beneficiary for AD patients, including its effects on amyloid beta, oxidative stress, tau protein, gene expression, and cholinesterase enzymes. Results: According to the review of the literature, it has beneficial effects, especially in animal studies on Alzheimer's disease. Conclusion: However, more studies should be done on humans to find the exact mechanisms of garlic’s effects on AD patients. [ABSTRACT FROM AUTHOR]

S-allyl cysteine (SAC) is a garlic-derived compound with antioxidant properties. Restraint stress constitutes a rodent model mimicking different features of human stress. The effects of SAC on behavioral, biochemical and morphological endpoints of brain alterations induced by chronic restraint stress were evaluated in rats. Restraint stress sessions were performed every day for 6 h during 21 consecutive days. SAC (100 mg/kg, i.p.) was administered daily 30 min before every single stress session. Behavioral tests comprised anxiety-like and depression-like challenges. Biochemical and morphological endpoints were estimated in three brain regions: striatum, hippocampus and cortex. Stressed animals exhibited augmented anxiety-like behavior, depression and morphological alterations, and these changes were accompanied by increased oxidative damage, compensatory regulation of antioxidant enzymes, and increased corticosterone plasma levels. SAC prevented anxiety-like behavior elicited by chronic stress in rats, and reduced morphological and biochemical alterations. The protective actions of SAC are related to its antioxidant properties.

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

We have synthesized a series of S-allyl cysteine ester-caffeic acid amide hybrids and evaluated them in order to determine their possible anticancer activity and selectivity in colorectal cancer, which is still one of the leading causes of morbidity and mortality worldwide. All compounds were tested against SW480 human colon adenocarcinoma cells and the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 6e, 9a, 9b, 9c, and 9e exhibited the highest effect on viability (IC50 SW480-48h= 0.18, 0.12, 0.12, 0.11, and 0.12 mM, respectively) and selectivity (SI = 10.3, 1.5, >83.33, >90.91 and >83.33, respectively) in a time- and concentration-dependent manner. Besides, our results were even better as regards lead compounds (S-allyl cysteine and caffeic acid) and the standard drug (5-FU). Additionally, these five compounds induced mitochondrial depolarization that could be related with an apoptotic process. Moreover, hybrids 6e, 9a, and 9e induced cell cycle arrest in G2/M phase, and compound 9c in S- phase, which suggests that these hybrid compounds could have also a cytostatic effect in SW480 cell line. The SAR analysis showed that hydroxyl groups increased the activity. Besides, there was not a clear relationship between the antitumor properties and the length of the alkyl chain. Since hybrid compounds were much more selective than the conventional drug (5-FU), this makes them promising candidates for further studies against colorectal cancer. [ABSTRACT FROM AUTHOR]

• BG showed possessed the inhibitory ability of DPPH and ABTS. • BG could improve RE-induced oxidative stress in the esophagus of rats. • BG may be more effective than RG in rat reflux esophagitis model. • BG effected of that the inactivation of NF-κB by blocking the degradation of IκBα. • BG led to the suppression of the release of proinflammatory cytokines. The present study was conducted to determine whether black garlic (BG) which is aged by pectinase treatment with high hydrostatic pressure processing has the protective effects in experimental model of acute reflux esophagitis (RE). BG was orally administered at a dose of 100 mg/kg body weight 2 h prior to induction of RE, and the effects were compared with those of raw garlic (RG). Esophageal pathological changes were analyzed using gross and histological examinations. The anti-oxidant and inflammatory protein levels were determined using western blotting. Moreover, RE-induced histological change was markedly suppressed by BG rather than RG. The reduced catalase was increased significantly by BG supplementation; however, superoxide dismutase levels showed a tendency to increase in the esophagus. Overall, the ameliorative effects of BG were superior to those when RG. These data reveal that that BG treatment ameliorates the development of esophagitis via regulation of NF-κB mediated inflammation. [ABSTRACT FROM AUTHOR]

Abstract Sepsis is a serious and life-threatening medical condition with a higher rate of patients' morbidity and mortality and with complications such as acute kidney injury (AKI). S-allyl cysteine (SAC) is the active constituent of the medicinal plant garlic (Allium sativum) with multiple beneficial effects including anti-inflammatory and antioxidant properties. In this research, we tried to determine the protective effect of SAC pretreatment in a mouse model of AKI. To induce AKI, lipopolysaccharide (LPS) was injected once (10 mg/kg, i.p.) and SAC was administered at doses of 25, 50, or 100 mg/kg (p.o.) 1 h before LPS. Treatment of LPS-challenged C56BL/6 animals with SAC lowered serum level of creatinine and blood urea nitrogen (BUN), partially restored renal oxidative stress-related biomarkers including malondialdehyde (MDA), glutathione (GSH), and activity of superoxide dismutase (SOD) and catalase in addition to improvement of mitochondrial membrane potential (MMP). Furthermore, SAC was capable to bring renal nuclear factor-kappaB (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), interleukin-6 (IL-6), Annexin V, and DNA fragmentation partially back to their control levels. Additionally, SAC pretreatment was capable to exert a protective effect, as shown histologically by lower tubular injury and pathologic changes in the kidney. In summary, SAC is capable to alleviate LPS-induced AKI through mitigation of renal oxidative stress, inflammation, and apoptosis in addition to preservation of mitochondrial integrity and its favorable effect exhibits a dose-dependent pattern. Highlights • SAC alleviated kidney function parameters in LPS model of AKI. • SAC attenuated renal oxidative stress in LPS model of AKI. • SAC improved renal antioxidants in LPS model of AKI. • SAC attenuated renal inflammation and apoptosis in LPS model of AKI. • SAC preserved mitochondrial integrity. [ABSTRACT FROM AUTHOR]

Abstract S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma. Graphical abstract Unlabelled Image Highlights • SAC is a compound present in garlic extract used as a traditional medicine. • SAC decreased AHR in OVA-induced asthma model. • SAC attenuated the production of Th2 cytokines in OVA-induced asthma model. • SAC reduced the expression of NF-κB and MUC5AC in OVA-induced asthma model. • SAC may be a potent therapeutic agent in allergic asthma. [ABSTRACT FROM AUTHOR]

Hypogonadism, associated with low levels of testosterone synthesis, has been implicated in several diseases. Recently, the quest for natural alternatives to prevent and treat hypogonadism has gained increasing research interest. To this end, the present study explored the effect of S-allyl cysteine (SAC), a characteristic organosulfur compound in aged-garlic extract, on testosterone production. SAC was administered at 50 mg/kg body weight intraperitoneally into 7-week-old BALB/c male mice in a single-dose experiment. Plasma levels of testosterone and luteinizing hormone (LH) and testis levels of proteins involved in steroidogenesis were measured by enzymatic immunoassay and Western blot, respectively. In addition, mouse testis-derived I-10 cells were also used to investigate the effect of SAC on steroidogenesis. In the animal experiment, SAC significantly elevated testosterone levels in both the plasma and the testis without changing the LH level in plasma and increased phosphorylated protein kinase A (p-PKA) levels. Similar results were also observed in I-10 cells. The findings demonstrating the increasing effect of SAC on p-PKA and mRNA levels of Cyp11a suggest that SAC increases the testosterone level by activating the PKA pathway and could be a potential target for hypogonadism therapeutics.

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.

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. [ABSTRACT FROM AUTHOR]

Abstract S-allyl cysteine (SAC) is known for its various beneficial effects such as neuroprotection and immunomodulation. The beneficial effect of SAC against gout has not been explored. The present study aims to describe the two roles of SAC: (1) inhibitory effect against xanthine oxidase (XO) enzyme activity; and (2) anti-inflammatory property against MSU crystal-induced gouty inflammation in rat. The inhibitory effect of SAC against bovine XO enzyme activity was determined in vitro. In silico analysis was carried out to determine the intermolecular interaction between SAC and bovine XO. MSU crystal was injected in the right paw of the rat to induce gouty inflammation. SAC (40 mg/kg body weight) and colchicine (positive control; 1 mg/kg body weight) was given for 3 days. At the end of the treatment, the oxidative stress, antioxidant parameters and mitochondrial function were determined in the ankle joint tissue. The concentration of inflammatory cytokines such as TNF-α and IL-1β was measured in the serum using ELISA. SAC inhibited (IC 50 value, 33 μg/ml) XO enzyme activity in a competitive mode with corresponding Ki value of 4 μg/ml. In silico analysis predicted the interaction of SAC with the amino acids such as Arg880, Phe798, Phe914 and Phe1009 of XO enzyme. The root mean square deviation, root mean square fluctuation and free energy calculation values confirmed the stable SAC-XO interaction. The inhibition of SAC on XO enzyme activity in in vivo was further confirmed by silkworm model. SAC through reducing oxidative stress, enhancing antioxidants, protecting mitochondrial function has shown anti-inflammatory effect against MSU crystal-induced gout which was observed as reduced level of inflammatory markers in the serum. The medicinal potential of SAC as a preventive agent through its XO inhibitory property as well as curative agent through its anti-inflammatory property against gout has been understood from the present study. Highlights • S-allyl cysteine (SAC) inhibited xanthine oxidase (XO). • In silico analysis predicted binding of SAC in the active site of XO. • XO reduced MSU crystal-induced paw swelling in rat gout model. • SAC showed anti-inflammatory effect against MSU crystal-induced gout. [ABSTRACT FROM AUTHOR]

In humans, alpha-glucosidase activity is present in sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM). α-glucosidase is involved in the hydrolyses of disaccharide into monosaccharides and results in hyperglycemia. Subsequently chronic hyperglycemia induces oxidative stress and ultimately leads to the secondary complications of diabetes. Hence, identifying compounds with dual beneficial activity such as efficient antioxidant and α-glucosidase inhibition property has attracted the attention in recent years. Keeping these views, in the present study astaxanthin (AST; a natural antioxidant present in marine microalgae) was biconjugated with allyl sulfur amino acid such as s-allyl cysteine (SAC). The synthesized AST-SAC (with molecular weight of 883.28) was characterized using UV–visible spectrophotometer, ESI-MS, and NMR analysis. AST-SAC showed potent antioxidant property in vitro . AST-SAC inhibited Saccharomyces cerevisiae α-glucosidase (IC 50  = 3.98 μM; Ki = 1 μM) and mammalian α-glucosidase [rat intestinal maltase (IC 50  = 6.4 μM; Ki = 1.3 μM) and sucrase (IC 50  = 1.6 μM; Ki = 0.18 μM)] enzyme activity in a dose-dependent manner. Kinetic analysis revealed that AST-SAC inhibited all the α-glucosidases in a competitive mode. In silico analysis determined the interaction of AST-SAC with the amino acids present in the active site of S. cerevisiae and human (MGAM and SI) α-glucosidases. [ABSTRACT FROM AUTHOR]

S-allyl cysteine (SAC) has antioxidant, antidiabetic and antiobesity properties. We hypothesized that neonatal oral administration of SAC would protect rats against neonatal and adulthood high-fructose diet-induced adverse metabolic outcomes in adulthood. In total, 112 (males=56; females=56), 4-day-old Wistar rat pups were randomly allocated to groups and administered the following treatment regimens daily for 15 days from postnatal day (PND) 6–20: group I – 10 ml/kg distilled water, group II – 10 ml/kg 20% fructose solution (FS), group III – 150 mg/kg SAC and group IV – SAC+FS. On PND 21, the pups were weaned and allowed to grow on a standard rat chow (SRC) until PND 56. The rats from each treatment regimen were then randomly split into two subgroups: one on a SRC and plain drinking water and another on SRC and 20% FS as drinking fluid and then subjected to these treatment regimens for 8 weeks after which they were euthanized and tissues collected for analyzes. Neonatal oral administration of SAC attenuated the neonatal high-fructose diet-induced programming for hepatic lipid accretion in adulthood but not against adulthood high-fructose diet-induced visceral obesity. Neonatal oral administration of SAC programmes for protection against neonatal fructose-induced programming for hepatic lipid accumulation thus could potentially protect against fat-mediated liver derangements in adult life. [ABSTRACT FROM PUBLISHER]

S-allyl cysteine (SAC), has shown itself to performance important activity as a neuroprotective agent. This action is prompted by antioxidative activity. The aim of this study was to evaluate the neuroprotective effect of SAC, the principal organosulfur compound of garlic, on experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS). Young-adult Dark Agouti rats were used. The experimental model of EAE was carried out by means of mielyn oligodendrocyte glycoprotein (MOG). The effects of MOG were evaluated by changes in: clinical score, biomarkers of oxidative/nitrosative stress, antioxidants, mitochondrial viability and neurohistologic viability. Our results reveal that MOG causes oxidative/nitrosative damage in brain and spinal cord, a decrease in the glutathione redox system and cell loss, whereas SAC administration attenuates the effects of MOG. In addition, SAC was the most effective treatment used in this study. The data show the ability of SAC to modify the development of EAE. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a deleterious autoimmune and demyelinating disorder of the central nervous system with debilitating sensory and motor complications. There is still no definite cure for it and the main focus for its treatment mostly pivots around subsiding its severity and recurrence. Experimental autoimmune encephalomyelitis (EAE) is an established animal model of MS. S-allyl cysteine (SAC) is the active and main constituent of aged garlic extract with anti-inflammatory and neuroprotective property. This study was conducted to evaluate its possible protective effect in EAE model of MS. SAC was administered p.o. at a dose of 50 mg/kg/day to female C57BL/6 mice immunized with myelin oligodendrocytic glycoprotein (MOG 35-55 ). Results showed that SAC is capable to alleviate clinical signs and severity of the disease and improved lumbar spinal cord tissue level of tumor necrosis factor α (TNFa), interleukin 17 (IL-17), activity-dependent neuroprotector homeobox (ADNP), microtubule-associated proteins 1A/1 B light chain 3A (MAP1LC3A), and matrix metalloproteinase 9 (MMP-9). In addition, SAC attenuated inflammatory cell infiltration, axonal demyelination, and axonal loss in lumbar spinal cord in EAE group, as demonstrated by H & E, Luxol fast blue (LFB), and Bielschowsky silver staining, respectively. Taken together, SAC could mitigate severity of MOG 35-55 -induced EAE as a valid model of MS via amelioration of pathogenic molecular mechanisms responsible for neuroinflammation and axonal damage. [ABSTRACT FROM AUTHOR]

Garlic is a component of the Mediterranean diet. S-allyl cysteine (SAC), the most common organosulphur present in garlic, possesses neuroprotective properties. This investigation was performed to evaluate the dose-dependent protective action of SAC on oxidative damage, inflammation and gut microbiota alterations biomarkers. Experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS) was induced by the myelin oligodendrocyte glycoprotein (MOG), whose effects were quantified by examining the changes in: clinical score, lipid peroxidation products, carbonylated proteins, glutathione system, tumor necrosis factor alpha (TNFα), and lipopolysaccharide membrane bacteria (LPS). Our results reveal that MOG induces paralysis, oxidative damage and increases in LPS binding protein (LBP) and LPS levels. In this work, two doses of SAC were compared with two dose of N-acetyl cysteine (NAC). SAC was more effective than NAC and it prevented the harmful effects induced by MOG more effectively at the dose of 50 mg/kg than that of 18 mg/kg. Surprisingly, NAC increases LBP levels while SAC had not such negative effect. In conclusion the data show the ability of SAC to modify EAE evolution. [ABSTRACT FROM AUTHOR]

Hexavalent chromium (Cr (VI)) is a common environmental pollutant. Cr (VI) exposure can lead to severe damage to the liver, but the preventive measures to diminish Cr (VI)-induced hepatotoxicity need further study. S-allyl cysteine (SAC) is a constituent of garlic (Allium sativum) and has many beneficial effects to humans and rodents. In this study, we intended to analyze the mechanistic role of SAC during Cr (VI)-induced hepatotoxicity. Male Wistar albino rats were induced with 17 mg/kg body weight to damage the liver. The Cr (VI)-induced rats were treated with 100 mg/kg body weight of SAC as an optimum dosage to treat hepatotoxicity. We observed that the levels of oxidants, lipid peroxidation and hydroxyl radical (OH•) were increased, and enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were found to be decreased in Cr (VI)-induced rats. While treated with SAC, the levels of oxidants were decreased and enzymatic antioxidants were significantly (p < 0.05) increased. Lysosomal enzyme activities were increased in Cr (VI)-induced rats and on treatment with SAC, the activities were significantly decreased. The expressions of nuclear factor-kappa B (p65-NF-κB), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) were increased during induction with Cr (VI). Subsequent administration of SAC to animals showed a decrease in the expressions of NF-κB, TNF-α, and iNOS. Results obtained from this study clearly demonstrated that SAC protects the liver cells from the Cr (VI)-induced free radical damage. [ABSTRACT FROM AUTHOR]

S-allyl cysteine (SAC) is a garlic-derived compound with antioxidant properties. Restraint stress constitutes a rodent model mimicking different features of human stress. The effects of SAC on behavioral, biochemical and morphological endpoints of brain alterations induced by chronic restraint stress were evaluated in rats. Restraint stress sessions were performed every day for 6 h during 21 consecutive days. SAC (100 mg/kg, i.p.) was administered daily 30 min before every single stress session. Behavioral tests comprised anxiety-like and depression-like challenges. Biochemical and morphological endpoints were estimated in three brain regions: striatum, hippocampus and cortex. Stressed animals exhibited augmented anxiety-like behavior, depression and morphological alterations, and these changes were accompanied by increased oxidative damage, compensatory regulation of antioxidant enzymes, and increased corticosterone plasma levels. SAC prevented anxiety-like behavior elicited by chronic stress in rats, and reduced morphological and biochemical alterations. The protective actions of SAC are related to its antioxidant properties. [ABSTRACT FROM AUTHOR]

In spite of the tremendous stride in modern medicine, conventional drugs used in the hepatotoxic management are mostly inadequate. The present study aims in the synthesis of novel Schiff base compound derived using s-allyl cystiene and methionine. The newly synthesized compound, 2-((2-((2-(allylthio)-1-carboxyethyl)imino)ethylidene)amino)-4-(methylthio)butanoic acid (ACEMB) was characterized using UV–visible spectrophotometer, FTIR, 1 HNMR, and GC-MS. ACEMB showed potent in vitro antioxidant property. Chronic administration of ACEMB prior to CCl 4 intoxication: i) attenuated the leakage of liver injury markers, such as, enzymes (AST, ALT, GGT, ALP and LDH) and biomolecules (bilirubin) into the blood circulation; ii) normalized the concentration of total proteins, albumin and globulin to control level; and iii) protected the liver against dyslipidemia. These effects of ACEMB show the preservation of endoplasmic reticulum function against CCl 4 toxicity in the liver. The protective effect of ACEMB was due to its antioxidant property, which was revealed by reduced oxidative stress (TBARS and HP) and enhanced functions of the endogenous antioxidative system (SOD, catalase, GPx, GST, GSH, vitamin E and C) against CCl 4 intoxication. Also, ACEMB protected the functional activities of the various mitochondrial tricarboxylic acid cycle and oxidative phosphorylation enzymes. The biochemical alterations are in concurrence with the histological observations, wherein ACEMB pretreatment prevented the vacuolation, degeneration of nuclei and necrosis of hepatocytes. In addition, in silico analysis reveals the interaction of ACEMB in the active site of cytochrome P450. ACEMB mediates hepatoprotective effect by substituting itself as an antioxidant and decreasing oxidative stress, thereby diminishing the intracellular organelle dysfunction against CCl 4 toxicity in the liver. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0.15% SAC-containing diet from seven days prior to instillation up until the conclusion of the experiment (14 days post-instillation). SAC significantly reduced collagen mRNA expression and protein deposition (33.3 ± 2.7 μg/mg and 28.2 ± 2.1 μg/mg tissue in vehicle- and SAC-treated rats, respectively), and decreased fibrotic area, as assessed histologically. In the rats' lungs, SAC also attenuated the increased expression of transforming growth factor-β1 (TGF-β1), a central regulator of myofibroblast recruitmenţ activation, and differentiation. While bleomycin instillation increased the number of myofibroblasts within the lung mesenchymal area, this change was significantly reduced by SAC treatment. SAC may exert efficacy as an anti-fibrotic by attenuating myofibroblast differentiation through TGF-β1-mediated fibroproliferative processes. Thus, our results indicate SAC may be useful for the prevention or treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Multispectroscopic techniques were used to investigate the interaction of S-allyl cysteine (SAC) from garlic with human serum albumin (HSA). UV-Vis absorption measurements prove the formation of the HSA-SAC complex. An analysis of fluorescence spectra revealed that in the presence of SAC, the quenching mechanism of HSA is considered static. The quenching rate constant Kq, KSV, and the binding constant KA were estimated. According to the Van't Hoff equation, the thermodynamic parameters enthalpy change (ΔH) and entropy change (ΔS) were calculated to be -1.00 x 105 J/mol and -255 J/mol/K, respectively. These indicate that hydrogen bonds and van der Waals forces are the major forces between SAC and HSA. The changes in the secondary structure of HSA, which was induced by SAC, were determined by circular dichroism spectroscopy. Energy transfer was confirmed and the distance between donor and acceptor was calculated to be 2.83 nm. [ABSTRACT FROM AUTHOR]

Neuroinflammation is known as a risk factor for cognitive deficit and dementia and its incidence increases with aging. S-allyl cysteine (SAC) is the active and main component of aged garlic extract with anti-inflammatory, neuroprotective, and nootropic potential. In this study, the protective effect of SAC against lipopolysaccharide (LPS)-induced cognitive deficit in the rat was investigated. For induction of learning and memory impairment and neuroinflammation, LPS was intraperitoneally injected at a dose of 167 μg/kg for 7 days and SAC was administered p.o. at doses of 25, 50, or 100 mg/kg/day, 30 min after LPS, for seven days. Treatment of LPS-injected rats with SAC at a dose of 100 mg/kg improved spatial recognition memory in Y maze, discrimination ratio in novel object discrimination task, and retention and recall in passive avoidance test. In addition, SAC at the latter dose mitigated lipid peroxidation marker malondialdehyde (MDA) and augmented key antioxidant defensive elements including superoxide dismutase (SOD), catalase and glutathione (GSH) in hippocampal homogenate and lowered acetylcholinesterase activity. Meanwhile, SAC down-regulated hippocampal nuclear factor-B, toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and interleukin 1β (IL-1β) and up-regulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in addition to lowering iba1-immunoreactive intensity in the hippocampus of LPS-injected group. Taken together, SAC administration could mitigate LPS-induced cognitive deficits via attenuation of oxidative stress, neuroinflammation, astrogliosis, and acetylcholinesterase activity. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is associated with learning, memory, and cognitive deficits. S-allyl cysteine (SAC) is the main organosulfur bioactive molecule in aged garlic extract with anti-diabetic, antioxidant, anti-inflammatory and nootropic property. This research was conducted to evaluate the efficacy of SAC on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats and to explore involvement of toll-like receptor 4 (TLR4), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-kappa B (NF-κB), and heme oxygenase 1 (HO-1) signaling cascade. Male Wistar rats were divided into control, diabetic, SAC-treated diabetic, and glibenclamide-treated diabetic (positive control) groups. SAC was administered at a dose of 150 mg/kg for seven weeks. Treatment of diabetic rats with SAC lowered serum glucose, improved spatial recognition memory in Y maze, discrimination ratio in novel object recognition task, and restored step-through latency (STL) in passive avoidance paradigm. In addition, SAC reduced acetylcholinesterase activity, lipid peroxidation marker malondialdehyde (MDA) and augmented antioxidant defensive system including superoxide dismutase (SOD), catalase and reduced glutathione (GSH) in hippocampal lysate. Meanwhile, SAC lowered hippocampal NF-kB, TLR4, and TNFα and prevented reduction of Nrf2 and heme oxygenase-1 (HO-1) in diabetic rats. Taken together, chronic SAC treatment could ameliorate cognitive deficits in STZ-diabetic rats through modulation of Nrf2/NF-κB/TLR4/HO-1, and acetylcholinesterase and attenuation of associated oxidative stress and neuroinflammation. [ABSTRACT FROM AUTHOR]

In vitro cultivation systems for oocytes and embryos are characterised by increased levels of reactive oxygen species (ROS), which can be balanced by the addition of suitable antioxidants. S-allyl cysteine (SAC) is a sulfur compound naturally occurring in garlic (Allium sativum), which is responsible for its high antioxidant properties. In this study, we demonstrated the capacity of SAC (0.1, 0.5 and 1.0 mM) to reduce levels of ROS in maturing oocytes significantly after 24 (reduced by 90.33, 82.87 and 91.62%, respectively) and 48 h (reduced by 86.35, 94.42 and 99.05%, respectively) cultivation, without leading to a disturbance of the standard course of meiotic maturation. Oocytes matured in the presence of SAC furthermore maintained reduced levels of ROS even 22 h after parthenogenic activation (reduced by 66.33, 61.64 and 57.80%, respectively). In these oocytes we also demonstrated a growth of early embryo cleavage rate (increased by 33.34, 35.00 and 35.00%, respectively). SAC may be a valuable supplement to cultivation media.