s-allylcysteine and Brain-Ischemia

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

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

During cerebral ischemia, energy restoration through the regulation of glucose transporters and antioxidant defense mechanisms is essential to maintain cell viability. Antioxidant therapy has been considered effective to attenuate brain damage; moreover, the regulation of transcription factors that positively regulate the expression of glucose transporters is associated with this therapy. Recently, it has been reported that the use of antioxidants such as S-allylcysteine (SAC), a component of aged garlic extract (AGE), improves survival in experimental models of cerebral ischemia.. The aim of this study was to determine the effect of AGE and SAC on the level of mRNA expression of the main neuronal glucose transporter (GLUT3) and the glutamate cysteine ligase catalytic subunit (GCLC) in rats with transient focal cerebral ischemia.. Cerebral ischemia was induced in male Wistar rats by middle cerebral artery occlusion (MCAO) for 2 h. The animals were sacrificed after different reperfusion times (0-48 h). Animals injected with AGE (360 mg/kg, intraperitoneally (i.p.)) and SAC (300 mg/kg, i.p.) at the beginning of reperfusion were sacrificed after 2 h. The mRNA expression level was analyzed in the fronto-parietal cortex using quantitative polymerase chain reaction (qPCR).. Two major increases in GLUT3 expression at 1 h and 24 h of reperfusion were found. Both treatments increased GLUT3 and GCLC mRNA levels in control and under ischemic/reperfusion injury animals.. This data suggests that SAC and AGE might induce neuroprotection, while controlling reactive oxygen species (ROS) levels, as indicated by the increase in GCLC expression, and regulating the energy content of the cell by increasing glucose transport mediated by GLUT3.

Topics: Animals; Antioxidants; Brain Ischemia; Cysteine; Garlic; Glucose Transport Proteins, Facilitative; Glutamate-Cysteine Ligase; Male; Neuroprotective Agents; Plant Extracts; Rats; Rats, Wistar; Reperfusion Injury

Stroke is a devastating clinical condition for which an effective neuroprotective treatment is currently unavailable. S-allyl cysteine (SAC), the most abundant organosulfur compound in aged garlic extract, has been reported to possess neuroprotective effects against stroke. However, the mechanisms underlying its beneficial effects remain poorly defined. The present study tests the hypothesis that SAC attenuates ischemic neuronal injury by activating the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent antioxidant response in both in vitro and in vivo models. Our findings demonstrate that SAC treatment resulted in an increase in Nrf2 protein levels and subsequent activation of antioxidant response element pathway genes in primary cultured neurons and mice. Exposure of primary neurons to SAC provided protection against oxygen and glucose deprivation-induced oxidative insults. In wild-type (Nrf2(+/+) ) mice, systemic administration of SAC attenuated middle cerebral artery occlusion-induced ischemic damage, a protective effect not observed in Nrf2 knockout (Nrf2(-/-) ) mice. Taken together, these findings provide the first evidence that activation of the Nrf2 antioxidant response by SAC is strongly associated with its neuroprotective effects against experimental stroke and suggest that targeting the Nrf2 pathway may provide therapeutic benefit for the treatment of stroke. The transcription factor Nrf2 is involved in cerebral ischemic disease and may be a promising target for the treatment of stroke. We provide novel evidence that SAC confers neuroprotection against ischemic stroke by activating the antioxidant Nrf2 signaling pathway. ARE, antioxidant response element; GCLC, glutathione cysteine ligase regulatory subunit; GCLM, glutathione cysteine ligase modulatory subunit; HO-1, heme oxygenase-1; JNK, c-Jun N-terminal kinase; Keap1, Kelch-like ECH-associated protein 1; Maf, musculoaponeurotic fibrosarcoma; Nrf2, nuclear factor erythroid-2-related factor 2; SAC, S-allyl cysteine; ROS, reactive oxygen species.

Topics: Animals; Animals, Newborn; Brain Infarction; Brain Ischemia; Cells, Cultured; Cerebral Cortex; Cysteine; Disease Models, Animal; Embryo, Mammalian; Glucose; Hypoxia; In Situ Nick-End Labeling; L-Lactate Dehydrogenase; Mice; Mice, Transgenic; Neurologic Examination; Neurons; Neuroprotective Agents; NF-E2-Related Factor 2; Signal Transduction

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The present study examined the hypothesis that S-allyl cysteine (SAC), organosulfur compounds found in garlic extract, would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). To test this hypothesis, male Wistar rats were subjected to MCAO for 2 hours and 22-hour reperfusion. S-allyl cysteine was administered (100 mg/kg, b.wt.) intraperitoneally 30 minutes before the onset of ischemia and after the ischemia at the interval of 0, 6, and 12 hours. After 24 hours of reperfusion, rats were tested for neurobehavioral activities and were killed for the infarct volume, estimation of lipid peroxidation, glutathione content, and activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase). S-allyl cysteine treatment significantly reduced ischemic lesion volume, improved neurologic deficits, combated oxidative loads, and suppressed neuronal loss. Behavioral and biochemical alterations observed after MCAO were further associated with an increase in glial fibrillary acidic protein and inducible nitric oxide expression and were markedly inhibited by the treatment with SAC. The results suggest that SAC exhibits exuberant neuroprotective potential in rat ischemia/reperfusion model. Thus, this finding of SAC-induced adaptation to ischemic stress and inflammation could suggest a novel avenue for clinical intervention during ischemia and reperfusion.

Topics: Allium; Animals; Antioxidants; Behavior, Animal; Brain Ischemia; Cerebrum; Cysteine; Glial Fibrillary Acidic Protein; Infarction, Middle Cerebral Artery; Inflammation; Male; Nervous System Diseases; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Reperfusion Injury

S-Allyl-L-cysteine (SAC) has been shown to reduce ischemic injury due to its antioxidant activity. However, the antioxidant property of SAC has been controversial. The present study investigated the neuroprotective mechanism of SAC in cerebral ischemic insults. SAC decreased the size of infarction after transient or global ischemic insults. While it did not alter the N-methyl-D-aspartate excitotoxicity, SAC significantly scavenged the endogenously or exogenously produced ONOO- and reduced ONOO- cytotoxicity. In contrast, SAC has much lower scavenging activity against H2O2, O2*(-) or NO. Further, SAC inhibited the activity of extracellular signal-regulated kinase (ERK) increased in cultured neurons exposed to oxygen-glucose deprivation or in rat brain tissue after transient middle cerebral artery occlusion. The neuroprotective effect of SAC was mimicked by the ERK inhibitor U0125. The present results indicate that SAC exert its neuroprotective effect by scavenging ONOO- and inhibiting the ERK signaling pathway activated during initial hypoxic/ischemic insults.

Topics: Animals; Antioxidants; Brain; Brain Ischemia; Cysteine; Dose-Response Relationship, Drug; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Gerbillinae; Male; Mitochondria; Neuroglia; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley