lignans and Brain-Ischemia

Polyphenols are an important family of molecules of vegetal origin present in many medicinal and edible plants, which represent important alimentary sources in the human diet. Polyphenols are known for their beneficial health effects and have been investigated for their potential protective role against various pathologies, including cancer, brain dysfunctions, cardiovascular diseases and stroke. The prevention of stroke promoted by polyphenols relies mainly on their effect on cardio- and cerebrovascular systems. However, a growing body of evidence from preclinical models of stroke points out a neuroprotective role of these molecules. Notably, in many preclinical studies, the polyphenolic compounds were effective also when administered after the stroke onset, suggesting their possible use in promoting recovery of patients suffering from stroke. Here, we review the effects of the major polyphenols in cellular and in vivo models of both ischemic and hemorrhagic stroke in immature and adult brains. The results from human studies are also reported.

Topics: Animals; Brain Ischemia; Cerebral Hemorrhage; Diarylheptanoids; Ellagic Acid; Flavonoids; Gastrointestinal Microbiome; Humans; Hydrolyzable Tannins; Hydroxybenzoates; Lignans; Polyphenols; Stilbenes; Stroke; Subarachnoid Hemorrhage

Topics: Animals; Antioxidants; Brain Ischemia; Heme Oxygenase-1; Lignans; Mice; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase; Syringa

Alzheimer's Dementia (AD) and Vascular Dementia (VaD) are two main types of dementias for which no specific treatment is available. Chronic Cerebral Hypoperfusion (CCH) is a pathogenesis underlying AD and VaD that promotes neuroinflammatory responses and oxidative stress. Honokiol (HNK) is a natural compound isolated from magnolia leaves that can easily cross blood brain barrier and has anti-inflammatory and antioxidant effects. In the present study, the effects of HNK on astrocyte polarization and neurological damage in in vivo and in vitro models of chronic cerebral hypoperfusion were explored. We found that HNK was able to inhibit the phosphorylation and nuclear translocation of STAT3, A1 polarization, and reduce conditioned medium's neuronal toxicity of astrocyte under chronic hypoxia induced by cobalt chloride; STAT3 phosphorylation inhibitor C188-9 was able to mimic the above effects of HNK, suggesting that HNK may inhibit chronic hypoxia-induced A1 polarization in astrocytes via STAT3. SIRT3 inhibitor 3-TYP reversed, while Sirt3 overexpression mimicked the inhibitory effects of HNK on oxidative stress, STAT3 phosphorylation and nuclear translocation, A1 polarization and neuronal toxicity of astrocyte under chronic hypoxic conditions. For in vivo research, continuous intraperitoneal injection of HNK (1 mg/kg) for 21 days ameliorated the decrease in SIRT3 activity and oxidative stress, inhibited astrocytic STAT3 nuclear translocation and A1 polarization, and prevented neuron and synaptic loss in the hippocampal of CCH rats. Besides, HNK application improved the spatial memory impairment of CCH rats, as assessed with Morris Water Maze. In conclusion, these results suggest that the phytochemical HNK can inhibit astrocyte A1 polarization via regulating SIRT3-STAT3 axis, thus improving CCH-induced neurological damage. These results highlight HNK as novel treatment for dementia with underlying vascular mechanisms.

Topics: Animals; Astrocytes; Brain Ischemia; Dementia; Lignans; Rats; Sirtuin 3

Brain ischemia/reperfusion (I/R) injury is a common pathological process after ischemic stroke. Pinoresinol diglucoside (PDG) has antioxidation and anti-inflammation activities. However, whether PDG ameliorates brain I/R injury is still unclear. In this study, middle cerebral artery occlusion (MCAO) model was established with male C57BL/6 mice, and the mice were treated with 5 and 10 mg/kg PDG via intravenous injection, respectively. The neurological deficit, infarct volume, and brain water content were then evaluated. HE staining and Nissl staining were used to analyze neuron injury. Besides, enzyme-linked immunosorbent assay and colorimetry assay were used to examine the level of inflammatory markers and oxidative stress markers, and Western blot was used to detect the expressions of p-p65, Nrf2, and HO-1. It was revealed that PDG could significantly alleviate the MCAO-induced neurological dysfunction of the mice and reduce the infarct volume, brain water content, and neuron injury. PDG treatment decreased the levels of TNF-α, IL-1β, IL-6, NO, ROS, and MDA, and significantly increased the activities of SOD, GSH, and GSH-Px in the brain tissue of the mice. Additionally, PDG could repress the activation of p65 and promote Nrf2 and HO-1 expressions. In conclusion, PDG exerts anti-inflammatory and antioxidation effects via regulating the NF-κB pathway and Nrf2/HO-1 pathway, thereby reducing the I/R-induced brain injury of mice.

Topics: Animals; Brain; Brain Ischemia; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Lignans; Male; Membrane Proteins; Mice, Inbred C57BL; Middle Cerebral Artery; Neuroinflammatory Diseases; Neurons; NF-E2-Related Factor 2; Oxidative Stress; Reperfusion Injury

Epidemic modeling has been a key tool for understanding the impact of global viral outbreaks for over two decades. Recent developments of the COVID-19 pandemic have accelerated research using compartmental models, like SI, SIR, SEIR, with their appropriate modifications. However, there is a large body of recent research consolidated on homogeneous population mixing models, which are known to offer reduced tractability, and render conclusions hard to quantify. As such, based on our recent work, introducing the heterogeneous geo-spatial mobility population model (GPM), we adapt a modified SIR-V (susceptible-infected-recovered-vaccinated) epidemic model which embodies the idea of patient relapse from R back to S, vaccination of R and S patients (reducing their infectiousness), thus altering the infectiousness of V patients (from

Topics: Acute Lung Injury; Adherens Junctions; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antigens, CD; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; beta Catenin; Brain Ischemia; Cadherins; Carcinogenesis; Catalysis; Cell Line; Cells, Cultured; Curcuma; Curcumin; Dioxoles; Disease Models, Animal; Endothelial Cells; Epithelial Cells; Heme Oxygenase (Decyclizing); Humans; Inflammasomes; Intestinal Diseases; Intestinal Mucosa; Ischemic Stroke; Kidney Neoplasms; Lignans; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; NAD(P)H Dehydrogenase (Quinone); Nanostructures; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phytotherapy; Plant Extracts; Pneumonia; PPAR gamma; Proto-Oncogene Proteins c-akt; Pyroptosis; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reperfusion Injury; Respiratory Distress Syndrome; Sepsis; Sesamum; Signal Transduction; Silybin; Silybum marianum; Silymarin; Sirtuin 3; Titanium; Transfection; Treatment Outcome; White Matter

Schisandrin A (SCH) is a natural bioactive phytonutrient that belongs to the lignan derivatives found in

Topics: Animals; Brain Injuries; Brain Ischemia; Cell Differentiation; Cell Line; Cell Proliferation; Cyclooctanes; Lignans; Male; Mice; Neural Stem Cells; Phytochemicals; Polycyclic Compounds

The endoplasmic reticulum stress (ERS) and ERS-related neuronal apoptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. (-)-Clausenamide has been reported to be nootropic and improve learning and memory in amnesia animal models. However, whether (-)-Clau could protect neurons from ischemic injury and the possible mechanism needed further study. The present study aimed to explore the effects of (-)-Clau on primary cortical neurons treated with oxygen-glucose deprivation/reoxygenation (OGD/R).. Rat primary cortical neurons were used to set up an injury model of OGD/R which imitated the clinical I/R injury. Cell viability and apoptosis were measured by CCK-8 assay, LDH detection and TUNEL staining, respectively. The activation of GRP78/eIF2α-ATF4-CHOP signaling pathway, one of the three branches of ERS, and cleaved caspase-3, the apoptotic marker, were assessed by western blotting.. OGD/R induced activation of GRP78/eIF2α-ATF4-CHOP signaling pathway. (-)-Clau significantly attenuated OGD/R-induced decrease in the cellular viability and the activation of GRP78, eIF2α, ATF4 and CHOP. To further confirm the effect of (-)-Clau on OGD/R-induced ERS activation, the ERS inducer Tunicamycin (TM) was applied. TM significantly abolished (-)-Clau's protective effect against ERS and neuronal apoptosis, indicating that the protective effect of (-)-Clau was dependent on inhibiting ERS.. The present work demonstrated for the first time that (-)-Clau could reverse the activation of GRP78/eIF2α-ATF4-CHOP branch, thus inhibited ERS and the subsequent apoptosis induced by OGD/R and promoted cell viability in vitro. (-)-Clau could serve as a promising therapeutic agent in the treatment for ischemic stroke in the future.. ATF4: activating transcription factor-4; ATF6: activating transcription factor-6; CHOP: transcriptional induction of CCAAT/enhancer binding protein homologous protein; (-)-Clau: 3-hydroxy-4-phenyl-5a-hydroxybenzylN-methyl-g-lactam; eIF2α: eukaryotic initiation factor 2α; ER: endoplasmic reticulum; ERS: endoplasmic reticulum stress; GRP78: 78-kDa glucose regulated protein; I/R: ischemia/reperfusion; IRE1: inositol requiring enzyme-1; JNK: c-Jun N-terminal kinase; OGD/R: oxygen-glucose deprivation/reoxygenation; PERK: double-stranded RNA-dependent protein kinase-like ER kinase; TM: Tunicamycin; UPR: unfolded protein response.

Topics: Animals; Apoptosis; Brain Ischemia; Cell Survival; Endoplasmic Reticulum Stress; Female; Lactams; Lignans; Male; Neurons; Neuroprotective Agents; Primary Cell Culture; Rats, Wistar; Reperfusion Injury; Signal Transduction

I/R: schemia/reperfusion; IL: interleukin; MCAO/R: middle cerebral artery occlusion and reperfusion; NF-κB: nuclear; TLR4: Toll-like receptor 4; TNF-α: tumor necrosis factor-α.

Topics: Animals; Anti-Inflammatory Agents; Brain Ischemia; Cyclooctanes; Lignans; Male; NF-kappa B; Polycyclic Compounds; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4

Intracerebral haemorrhage (ICH) induces inflammation, which can cause severe secondary injury. Recent evidence has suggested that magnolol (MG) has a protective effect against ischaemic stroke through the inhibition of inflammation. However, the anti-inflammatory effect of MG in intracerebral haemorrhage (ICH) remains unclear. Here, we report that the protective effect of MG in a rat model of ICH can be achieved by anti-inflammatory processes. We found that MG administration significantly reduced the brain water content, restored the blood-brain barrier (BBB) and subsequently attenuated neurological deficits via decreasing the activation of glial cells, decreasing the infiltration of neutrophils and reducing the production of pro-inflammation factors (IL-1β, TNF-α and MMP-9) in a rat model of ICH. These results suggest that MG reduced inflammatory injury and improved neurological outcomes in ICH model.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Biphenyl Compounds; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Cerebral Hemorrhage; Cytokines; Disease Models, Animal; Inflammation; Lignans; Male; Neuroglia; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Stroke

In the present study, the neuroprotective potential of magnolol against ischemia-reperfusion brain injury was examined via in vivo and in vitro experiments. Magnolol exhibited strong radical scavenging and antioxidant activity, and significantly inhibited the production of interleukin‑6, tumor necrosis factor‑a and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7 cells when applied at concentrations of 10 and 50 µM, respectively. Magnolol (100 µM) also significantly attenuated oxygen‑glucose deprivation‑induced damage in neonatal rat hippocampal slice cultures, when administered up to 4 h following the insult. In a rat model of stable ischemia, compared with a vehicle‑treated ischemic control, pretreatment with magnolol (0.01‑1 mg/kg, intravenously) significantly reduced brain infarction following ischemic stroke, and post‑treatment with magnolol (1 mg/kg) remained effective and significantly reduced infarction when administered 2 h following the onset of ischemia. Additionally, magnolol (0.3 and 1 mg/kg) significantly reduced the accumulation of superoxide anions at the border zones of infarction and reduced oxidative damage in the ischemic brain. This was assessed by measuring the levels of NOX, malondialdehyde and myeloperoxidase, the ratio of glutathione/oxidized glutathione and the immunoreactions of 8‑hydroxy‑2'‑deoxyguanosine and 4‑hydroxynonenal. Thus, magnolol was revealed to protect against ischemia‑reperfusion brain damage. This may be partly attributed to its antioxidant, radical scavenging and anti‑inflammatory effects.

Topics: Animals; Antioxidants; Biphenyl Compounds; Brain; Brain Ischemia; Cell Line; Glucose; Lignans; Male; Mice; Neuroprotective Agents; Oxidative Stress; Oxygen; Rats, Sprague-Dawley; RAW 264.7 Cells; Reperfusion Injury

Magnolol, a neolignan compound isolated from traditional Chinese medicine Magnolia officinalis, has a potentially therapeutic influence on ischemic stroke. Previous studies have demonstrated that cerebral ischemia-reperfusion (I-R) and blood-brain barrier (BBB) are involved in the pathogeneses of stroke. Therefore, in vivo and in vitro studies were designed to investigate the effects of magnolol on I-R-induced neural injury and BBB dysfunction. In cerebral I-R model of mice, cerebral infarct volumes, brain water content, and the exudation of Evans blue were significantly reduced by intravenous injection with magnolol at the doses of 1.4, 7.0, and 35.0 μg/kg. When primary cultured microglial cells were treated with 1 μg/ml lipopolysaccharide (LPS) plus increasing concentrations of magnolol, ranging from 0.01 to 10 μmol/L, magnolol could statistically inhibit LPS-induced NO release, TNF-α secretion, and expression of p65 subunit of NF-κB in the nucleus of microglial cells. In the media of brain microvascular endothelial cells (BMECs), oxygen and glucose deprivation-reperfusion (OGD-R) could remarkably lead to the elevation of TNF-α and IL-1β levels, while magnolol evidently reversed these effects. In BBB model in vitro, magnolol dose- and time-dependently declined BBB hyperpermeability induced by oxygen and glucose deprivation (OGD), OGD-R, and ephrin-A1 treatment. More importantly, magnolol could obviously inhibit phosphorylation of EphA2 (p-EphA2) not only in ephrin-A1-treated BMECs but also in cerebral I-R model of mice. In contrast to p-EphA2, magnolol significantly increased ZO-1 and occludin levels in BMECs subjected to OGD. Taken together, magnolol can protect neural damage from cerebral ischemia- and OGD-reperfusion, which may be associated with suppressing cerebral inflammation and improving BBB function.

Topics: Animals; Biphenyl Compounds; Blood-Brain Barrier; Brain Ischemia; Dose-Response Relationship, Drug; Interleukin-1beta; Lignans; Mice; Microglia; Nitric Oxide; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptor, EphA2; Reperfusion Injury; Tumor Necrosis Factor-alpha

Toll-like receptor 4 (TLR4) and C5aR1 (CD88) have been recognized as potential therapeutic targets for the reduction of inflammation and secondary damage and improvement of outcome after ischemia and reperfusion (I/R). The inflammatory responses which induce cell apoptosis and necrosis after I/R brain injury lead to a limited process of neural repair. To further comprehend how these targets function in I/R state, we investigated the pathological changes and TLR4 and C5aR1 signaling pathways in vitro and in vivo models of I/R brain injury in this study. Meanwhile, we explored the roles of schisantherin A on I/R brain injury, and whether it exerted neuroprotective effects by regulating the TLR4 and C5aR1 signaling pathways or not. The results showed that schisantherin A significantly reduced the neuronal apoptosis induced by oxygen and glucose deprivation and reperfusion (OGD/R) injury in primary culture of rat cortical neurons. Also, schisantherin A alleviated neurological deficits, reduced infarct volume, attenuated oxidation stress, inflammation and apoptosis in ischemic parietal cortex of rats after middle cerebral artery occlusion and reperfusion (MCAO/R) injury. Moreover, the activated TLR4 and C5aR1 signaling pathways were inhibited by schisantherin A treatment. In conclusion, TLR4 and C5aR1 played a vital role during I/R brain injury in rats, and schisantherin A exhibited neuroprotective effects by TLR4 and C5aR1 signaling pathways. These findings also provided new insights that would aid in elucidating the effect of schisantherin A against cerebral I/R and support the development of schisantherin A as a potential treatment for ischemic stroke.

Topics: Animals; Apoptosis; Brain Ischemia; Cell Survival; Cerebral Cortex; Cyclooctanes; Dioxoles; Inflammation; Lignans; Necrosis; Neurons; Neuroprotective Agents; Oxidative Stress; Parietal Lobe; Primary Cell Culture; Rats, Sprague-Dawley; Receptor, Anaphylatoxin C5a; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4

SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.. Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.. Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.. NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.

Topics: Animals; Brain Ischemia; Cell Line; Cyclooctanes; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Humans; Lignans; Myocardial Ischemia; NF-kappa B; Oxidative Stress; PC12 Cells; Polycyclic Compounds; Protein Interaction Maps; Rats; Saponins; Signal Transduction; Systems Biology; Tumor Necrosis Factor-alpha

Growing evidence suggests that therapeutic strategies to modulate the post-ischemic inflammatory responses are promising approaches to improve stroke outcome. Although the endocannabinoid system has been emerged as an endogenous therapeutic target to regulate inflammation after stroke insult, the downstream mechanisms and their potentials for therapeutic intervention remain controversial. Here we identified trans- and cis-hinokiresinols as novel non-selective antagonists for two G-protein-coupled cannabinoid receptors, cannabinoid receptor type 1 and type 2. The Electric Cell-substrate Impedance Sensing and Boyden chamber migration assays using primary microglial cultures revealed that both hinokiresinols significantly inhibited an endocannabinoid, 2-arachidonoylglycerol-induced migration. Hinokiresinols modulated 2-arachidonoylglycerol-induced mitochondrial bioenergetics in microglia as evidenced by inhibition of ATP turnover and reduction in respiratory capacity, thereby resulting in impaired migration activity. In rats subjected to transient middle cerebral artery occlusion (1.5-h) followed by 24-h reperfusion, post-ischemic treatment with hinokiresinols (2 and 7-h after the onset of ischemia, 10 mg/kg) significantly reduced cerebral infarct and infiltration of ED1-positive microglial/macrophage cells into cerebral ischemic lesions in vivo. Co-administration of exogenous 2-AG (1 mg/kg, i.v., single dose at 2 h after starting MCAO) abolished the protective effect of trans-hinokiresionol. These results suggest that hinokiresinols may serve as stroke treatment by targeting the endocannabinoid system. Alteration of mitochondrial bioenergetics and consequent inhibition of inflammatory cells migration may be a novel mechanism underlying anti-ischemic effects conferred by cannabinoid receptor antagonists.

Topics: Animals; Arachidonic Acids; Brain Ischemia; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Cell Movement; Cell Respiration; Cells, Cultured; Disease Models, Animal; Endocannabinoids; Glycerides; Lignans; Macrophages; Male; Microglia; Mitochondria; Phenols; Rats

Stroke is one of the leading causes of neuronal death. Sesamin is known for neuroprotection by its antioxidant and anti-inflammatory properties but it lacks blood-brain barrier (BBB) activity. A panel of sesamin derivatives was screened and 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) was selected for high BBB activity and tested for its neuroprotective effect.. The focal cerebral ischemia of Sprague-Dawley rats and hypoxia models of murine BV-2 microglia or PC12 cells under oxygen/glucose deprivation were used for in vivo and in vitro test, respectively. Lipid peroxidation and superoxide dismutase (SOD) activity from the ischemic brain were tested and reactive oxygen species (ROS), cytokine production, prostaglandin (PGE2) and related signaling pathways from hypoxic cells were examined by ELISA or Western blot assay, respectively.. BBD showed a protective effect when given 90 min after the focal cerebral ischemia. It also reduced lipid peroxidation and preserved SOD activity from the ischemic brain. The mechanism of BBD was further confirmed by attenuating ROS, cytokine production, and PGE2 release from hypoxic BV-2 or PC12 cells. BBD significantly reduced hypoxia-induced c-Jun N-terminal kinases (JNK) and modulated AKT-1 and caspase-3 (survival and apoptotic pathways) in BV-2 cells, and inhibited hypoxia-induced JNK and cyclooxygenase-2 activation in PC12 cells.. The neuroprotective effect of BBD on ischemia/hypoxia models was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of ischemia/hypoxia injury.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blood-Brain Barrier; Brain Ischemia; Butylene Glycols; Cell Hypoxia; Dioxoles; Humans; Lignans; Lipid Peroxidation; Mice; Microglia; Neurons; Neuroprotective Agents; Rats; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase

Brain ischemia appears to be associated with innate immunity. Recent reports showed that C3a and C5a, as potent targets, might protect against ischemia induced cell death. In traditional Chinese medicine, the fruit of Schizandra chinesis Baill (Fructus schizandrae) has been widely used as a tonic. In the present study, we sought to evaluate the neuroprotective effects of schizandrin A, a composition of S. chinesis Baill, against oxygen and glucose deprivation followed by reperfusion (OGD/R)-induced cell death in primary culture of rat cortical neurons, and to test whether C3a and C5a affected cortical neuron recovery from ischemic injury after schizandrin A treatment. The results showed that schizandrin A significantly reduced cell apoptosis and necrosis, increased cell survival, and decreased intracellular calcium concentration ([Ca(2+)]i) and lactate dehydrogenase (LDH) release in primary culture of rat cortical neurons after OGD/R. Mechanism studies suggested that the modulation of extracellular-regulated kinase (ERK), c-Jun NH2-terminal kinases (JNK), and p38, as well as caspase-3 activity played an important role on the progress of neuronal apoptosis. C5aR participated in the neuroprotective effect of schizandrin A in primary culture of rat cortical neurons after OGD/R. Our findings suggested that schizandrin A might act as a candidate therapeutic target drug used for brain ischemia and related diseases.

Topics: Animals; Apoptosis; Brain Ischemia; Calcium; Caspase 3; Cell Death; Cell Hypoxia; Cell Survival; Cells, Cultured; Cyclooctanes; Glucose; L-Lactate Dehydrogenase; Lignans; MAP Kinase Signaling System; Medicine, Chinese Traditional; Neurons; Neuroprotective Agents; Phytotherapy; Polycyclic Compounds; Rats; Receptor, Anaphylatoxin C5a; Receptors, G-Protein-Coupled; Reperfusion Injury; Schisandra; Signal Transduction

Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB.

Topics: Animals; Biphenyl Compounds; Blotting, Western; Brain; Brain Ischemia; Cell Death; Endoplasmic Reticulum Stress; Immunohistochemistry; Indicators and Reagents; Ischemic Attack, Transient; Lignans; Male; Neurons; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Oncogene Protein v-akt; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stroke; Transcription Factor CHOP; Tyrosine

To observe the effect of Schisandra chinensis lignans (SCL) on neuronal apoptosis and PI3K/AKT signaling pathway of rats in the cerebral ischemia injury model, and study its possible mechanism.. Rats were orally administered SCL high, middle and low dose groups (100, 50, 25 mg x kg(-1)) for 14 days. The cerebral ischemia injury model was established by using the suture-occluded method to rate the neurological functions. The cerebral infarction area was observed by TTC staining. The pathological changes in brain tissues were determined by HE staining. Bcl-2 and Bax expressions were detected by immunohistochemical assay. The protein expressions of p-AKT and AKT were assayed by Western blotting.. Compared with the model group, SCL high, middle and low dose groups showed reduction in the cerebral infarction area to varying degrees, improve the pathological changes in brain tissues, promote the expression of apoptin Bcl-2 and p-AKT, and inhibit the expression of apoptin Bax.. SCL shows a protective effect on rats with cerebral ischemia injury. Its mechanism may be related to the increase in p-AKT ability and antiischemic brain injury capacity and the inhibition of nerve cells.

Topics: Administration, Oral; Animals; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Immunohistochemistry; Lignans; Male; Neurons; Phosphatidylinositol 3-Kinases; Phosphorylation; Phytotherapy; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Schisandra; Signal Transduction

Stroke is a severe neurological disorder characterized by the abrupt loss of blood circulation into the brain resulting into wide ranging brain and behavior abnormalities. The present study was designed to evaluate molecular mechanism by which sesamin (SES) induces neuroprotection in mouse model of ischemic stroke. The results of this study demonstrate that SES treatment (30 mg/kg bwt) significantly reduced infarction volume, lipid per-oxidation, cleaved-caspase-3 activation, and increased GSH activity following MCAO in adult male mouse. SES treatment also diminished iNOS and COX-2 protein expression, and significantly restored SOD activity and protein expression level in the ischemic cortex of the MCAO animals. Furthermore, SES treatment also significantly reduced inflammatory and oxidative stress markers including Iba1, Nox-2, Cox-2, peroxynitrite compared to placebo MCAO animals. Superoxide radical production, as studied by DHE staining method, was also significantly reduced in the ischemic cortex of SES treated compared to placebo MCAO animals. Likewise, downstream effects of superoxide free radicals i.e. MAPK/ERK and P38 activation was also significantly attenuated in SES treated compared to placebo MCAO animals. In conclusion, these results suggest that SES induces significant neuroprotection, by ameliorating many signaling pathways activated/deactivated following cerebral ischemia in adult mouse.

Topics: Animals; Brain Ischemia; Dioxoles; Disease Models, Animal; Encephalitis; Infarction, Middle Cerebral Artery; Lignans; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Oxidative Stress; Signal Transduction; Stroke

This study was designed to investigate the effects of honokiol, a neuroprotective agent, on cerebral edema in cerebral ischemia reperfusion (IR) mice and its mechanism of anti-inflammation. Honokiol (0.7-70μg/kg) significantly reduced brain water contents and decreased the exudation of Evans blue dye from brain capillaries in cerebral IR mice. Honokiol (0.1-10μM) significantly reduced the p65 subunit level of NF-κB in the nucleus of primary culture-microglia. It (0.01-10μM) evidently reduced nitric oxide (NO) level in the microglia culture medium and in the microglia and astrocytes coculture medium. Honokiol (0.01-10μM) significantly decreased the level of TNF-α in the microglia medium or coculture cell medium. Honokiol (10μM) decreased the level of Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES/CCL5) protein in medium of microglia or astrocytes. In conclusion, Honokiol has a potent anti-inflammatory effect in cerebral ischemia-reperfusion mice and this effect might be attributed to its inhibition ability on the NF-κB activation, consequently blocking the production of inflammatory factors including: NO, tumor necrosis factor-α (TNF-α) and RANTES/CCL5 in glial cells. These results provide evidence for the anti-inflammatory effect of honokiol for the potential treatment of ischemic stroke.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Biphenyl Compounds; Brain Edema; Brain Ischemia; Capillary Permeability; Chemokine CCL5; Coculture Techniques; Cytokines; Drugs, Chinese Herbal; Female; Inflammation; Lignans; Male; Mice; Microglia; Neuroglia; NF-kappa B; Nitric Oxide; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha

During cerebral ischemia, neurons are injured by various mechanisms including excitotoxicity, oxidative stress, and inflammatory responses. Thus, pharmacological manipulation of multiple cytotoxic pathways has been pursued for the treatment of ischemic injury. Cis-hinokiresinol, a naturally occurring phenylpropanoid, was previously reported to possess anti-oxidant, anti-inflammatory and estrogen-like activities. In the present study, we investigated anti-ischemic effects of trans- and cis-hinokiresinols using in vitro as well as in vivo experimental models. The ORAC and DPPH assays showed that two isomers had similar free radical scavenging activities. However, only trans-hinokiresinol significantly decreased neuronal injury in cultured cortical neurons exposed to oxygen-glucose deprivation (75 min) followed by re-oxygenation (9 h). The differential neuroprotective effect could be due to the stereo-specific augmentation of Cu/Zn-SOD activity by trans-hinokiresinol, when compared with cis-hinokiresinol. Similarly, in rats subjected to transient middle cerebral artery occlusion (1.5 h) followed by 24-h reperfusion, pre-ischemic treatment with trans-hinokiresinol, but not with cis-isomer, reduced cerebral infarct volume. Interestingly, however, post-ischemic treatment with both hinokiresinols (2 and 7 h after onset of ischemia) significantly reduced cerebral infarct. When administered after onset of ischemia, trans-hinokiresinol, but not its cis-isomer reduced nitrotyrosine immunoreactivity in ischemic regions. In contrast, both hinokiresinols suppressed neutrophil infiltration and IL-1β release to a similar extent. The observed differential anti-oxidant, but comparable anti-inflammatory, activities may explain the stereo-specific anti-ischemic activities and different therapeutic time windows of the hinokiresinols examined. More detailed delineation of the anti-ischemic mechanism(s) of hinokiresinols may provide a better strategy for development of efficacious regimens for cerebral ischemic stroke.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Brain Ischemia; Cells, Cultured; Lignans; Male; Phenols; Rats; Rats, Sprague-Dawley; Stereoisomerism; Time Factors; Treatment Outcome

Honokiol, a constituent of Magnolia obovata, has various pharmacological effects, including protection against cerebral ischemia. However, few studies have been conducted to evaluate the possible neuroprotective effects of honokiol against cerebral ischemia. We recently reported that cerebral ischemic neuronal damage could be triggered by glucose intolerance that develops after the onset of ischemic stress (i.e., post-ischemic glucose intolerance). In addition, suppression of post-ischemic glucose intolerance significantly ameliorated ischemic neuronal damage. Here, we investigated the effects of honokiol on the development of post-ischemic glucose intolerance and neuronal damage. Mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. The development of post-ischemic glucose intolerance on day 1 and neuronal damage on day 3 after MCAO were significantly reduced by intraperitoneal administration of honokiol (10 mg/kg) compared with the vehicle-treated group. Honokiol did not affect serum insulin or adiponectin levels. However, honokiol significantly decreased the expression of phosphoenolpyruvate carboxykinase and increased the expression of 5'-AMP-activated protein kinase (AMPK) on day 1 after MCAO, compared with the vehicle-treated MCAO group. The results of this study suggest that honokiol could prevent post-ischemic glucose intolerance in an AMPK-dependent manner, which may be involved in the neuroprotective effects of honokiol against cerebral ischemia.

Topics: Adiponectin; AMP-Activated Protein Kinases; Animals; Biphenyl Compounds; Brain Ischemia; Glucose Intolerance; Infarction, Middle Cerebral Artery; Insulin; Lignans; Male; Mice; Phosphoenolpyruvate Carboxykinase (ATP)

Topics: Animals; Brain Ischemia; Disease Models, Animal; Disease Progression; Electrophysiology; Evoked Potentials, Somatosensory; Guaiacol; Lignans; Neuroprotective Agents; Prospective Studies; Rats; Stroke; Treatment Outcome

Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to enhance mitochondrial antioxidant status in liver, heart and brain tissues in rodents. Whether or not long-term Sch B treatment can protect against oxidative stress-induced cerebral damage remains unclear. In the present study, the effect of long-term Sch B treatment (1-30 mg/kg/dx15) on cerebral ischemia/reperfusion (I/R) injury was examined in rats. Sch B treatment protected against I/R-induced cerebral damage, as evidenced by the significant increase in the percentage of 2,3,5-triphenyl tetrazolium chloride (TTC)-stained tissues in representative brain slices, when compared with the Sch B-untreated and I/R control. The cerebroprotection was associated with an enhancement in cerebral mitochondrial antioxidant status, as assessed by the level/activity of reduced glutathione, alpha-tocopherol and Mn-superoxide dismutase, as well as the improvement/preservation of mitochondrial structural integrity, as assessed by the extents of malondialdehyde production, Ca(2+) loading and cytochrome c release, as well as the sensitivity to Ca(2+)-induced permeability transition, in control and I/R-challenged rats. In conclusion, long-term Sch B treatment could enhance cerebral mitochondrial antioxidant status as well as improve mitochondrial structural integrity, thereby protecting against I/R injury.

Topics: alpha-Tocopherol; Animals; Antioxidants; Area Under Curve; Brain Ischemia; Cyclooctanes; Female; Fruit; Glutathione; Lignans; Malondialdehyde; Mitochondria; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Schisandra; Superoxide Dismutase

Honokiol, a component of the herb Magnolia officinalis, exhibits antioxidant, anti-inflammatory and anxiolytic properties, increases seizure threshold, and promotes neurite outgrowth. Because stroke has become the second leading cause of death in industrialized countries, an effective neuroprotectant is urgently required. In this study, we attempted to elucidate in a mouse cerebral ischaemia model whether honokiol could be a neuroprotectant. Adult male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion for 45 min. Honokiol (10 microg/kg in 0.2 ml of saline) or control vehicle was intraperitoneally administered twice, 15 min. before and 60 min. after the induction of ischaemia. Cerebral ischaemia induced by this method was associated with an increase in synaptosomal production of reactive oxygen species, with decreases in synaptosomal mitochondrial membrane potential (DeltaPsim) and synaptosomal mitochondrial metabolic function, and with reductions in Na(+), K(+)-ATPase activities of tissues isolated from selected brain regions. Administration of honokiol resulted in significant reductions in brain infarct volume and in synaptosomal production of reactive oxygen species. The decreases in synaptosomal mitochondrial membrane potential, synaptosomal mitochondrial metabolic function and tissue Na(+), K(+)-ATPase activities observed in the ischaemic brains were also attenuated by honokiol treatments. It is concluded that honokiol can protect brain against ischaemic reperfusion injury and preserve mitochondrial function from oxidative stress. Regarding therapeutic application, further studies are needed to assess the efficacy and safety of honokiol in clinical situations.

Topics: Animals; Anti-Anxiety Agents; Biphenyl Compounds; Brain Ischemia; Lignans; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred ICR; Neuroprotective Agents; Reactive Oxygen Species; Sodium-Potassium-Exchanging ATPase; Synaptosomes

To observe the effect and mechanism of clausenamide on the expression of Bcl-2 and apoptosis after focal cerebral ischemia/reperfusion in renovascular hypertensive rats.. Seventy-five renovascular hypertensive rats were randomly divided into three groups (25 in each group): clausenamide intervention group, single ischemia/reperfusion model group and sham-operated group. Focal cerebral ischemia was reproduced by ligature for 2 hours and loosening of the ligature in the rats. No arterial ligature was applied in sham-operated group. Computerized pathological image analyzer was used to determine the number of cells positive for Bcl-2 by immunohistochemical staining, and also the counts of apoptotic cells after TdT-mediated dUTP nick end labeling (TUNEL) staining respectively in coronal sections of brain after reperfusion (6, 12, 24, 48 and 72 hours).. (1) The expression of Bcl-2 protein was detected 6 hours after reperfusion, peaking at 24 hours, then declined gradually. The Bcl-2 protein positive cell counts at every time point in clausenamide intervention group were significantly higher than simple ischemia/reperfusion model group (all P<0.01). (2) The number of apoptotic cells was increased with reperfusion, reaching its peak at 72 hours. The apoptosis counts in clausenamide intervention group were significantly lower than single ischemia/reperfusion model group (all P<0.01). At all time points, except at 48 hours after reperfusion, as there was no significant difference (all P>0.05). No Bcl-2 positive cells and only 0-2 apoptotic cells could be discernible in brain sections from sham-operated animals or in the contralateral side of ischemia in animals of the other groups.. Expression of Bcl-2 protein is enhanced and apoptosis appears after focal cerebral ischemia/reperfusion in rat brain. Clausenamide can enhance the expression of Bcl-2 protein and inhibit apoptosis remarkably. Clausenamide may coordinate with Bcl-2 in inhibiting apoptosis. This may be the mechanism of protection of brain cells from ischemic damage of clausenamide treatment.

Topics: Animals; Apoptosis; Brain Ischemia; Disease Models, Animal; Hypertension; Lactams; Lignans; Male; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury

Acute neuroprotective effects of cinnamophilin (CINN; (8R, 8'S)-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan), a novel antioxidant and free radical scavenger, were studied in a mouse model of transient middle cerebral artery (MCA) occlusion. CINN was administered intraperitoneally either 15 min before (pretreatment) or 2 h after the onset of MCA occlusion (postischemic treatment). Relative to vehicle-treated controls, animals pretreated with CINN, at 20-80 mg/kg, had significant reductions in brain infarction by 33-46% and improvements in neurobehavioral outcome. Postischemic administration with CINN (80 mg/kg) also significantly reduced brain infarction by 43% and ameliorated neurobehavioral deficits. Additionally, CINN administration significantly attenuated in situ accumulation of superoxide anions (O2-) in the boundary zones of infarct at 4 h after reperfusion. Consequently, CINN-treated animals exhibited significantly decreased levels of oxidative damage, as assessed by immunopositive reactions for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE), and the resultant inflammatory reactions at 24 h post-insult. It is concluded that CINN effectively reduced brain infarction and improved neurobehavioral outcome following a short-term recovery period after severe transient focal cerebral ischemia in mice. The finding of a decreased extent of reactive oxygen species and oxidative damage observed with CINN treatment highlights that its antioxidant and radical scavenging ability is contributory.

Topics: Animals; Antioxidants; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Free Radical Scavengers; Guaiacol; Infarction, Middle Cerebral Artery; Lignans; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Time Factors

Honokiol, a constituent extracted from Magnolia officinalis, had been shown be an antioxidant and an anti-platelet agent in biological systems with an anti-arrhythmic effect and a myocardial protective effect on ischemia-reperfusion injury. We examined the neuroprotective effect of honokiol in rats subjected to focal cerebral ischemia. Honokiol was administered intravenously either at fifteen minutes before right middle cerebral artery occlusion (pretreatment groups) or when both common carotid arteries clips were removed (treatment groups). The results showed that there was no significant hemodynamic change after intravenous infusion of honokiol at the dosages of 10(-8), 10(-7) and 10(-6) g/kg in both groups. However, honokiol significantly reduced the total volume of infarction at the doses of 10(-7) or 10(-6) g/kg in both pretreatment and treatment groups. This study suggests that honokiol is a potent neuroprotective agent in focal cerebral ischemia. This beneficial effect may be related to its antioxidant effect and anti-platelet aggregation activity.

Topics: Animals; Antioxidants; Biphenyl Compounds; Brain Ischemia; Dose-Response Relationship, Drug; Infarction, Middle Cerebral Artery; Infusions, Intravenous; Lignans; Magnolia; Male; Phytotherapy; Platelet Aggregation Inhibitors; Random Allocation; Rats; Rats, Long-Evans

We have previously shown that honokiol, an active component of Magnolia officinalis, displayed protective effect against focal cerebral ischemia-reperfusion (FCI/R) injury in rats. Production of reactive oxygen species (ROS) and infiltration of neutrophils to injured tissue play deleterious roles during cerebral ischemia. To study the mechanism(s) in mediating neuroprotective effect of honokiol, FCI/R-induced neutrophil infiltration and lipid peroxidation in brain tissue, and activation of neutrophils in-vitro were examined. Intravenous administration of honokiol (0.01-1.0 microg/kg) 15 min before (pretreatment) or 60 min after (post-treatment) middle cerebral artery occlusion reduced the total infarcted volume by 20-70% in dose-dependent manner. Pretreatment or post-treatment of honokiol at concentration of 0.1 and 1.0 microg/kg significantly decreased the neutrophil infiltration in the infarcted brain. Time course of neutrophil infiltration was performed in parallel with the lipid peroxidation in infracted brain tissue during FCI/R injury. The results indicate that honokiol can protect brain tissue against lipid peroxidation and neutrophil infiltration during FCI/R injury and cerebral infarction induced by FCI/R is accompanied with a prominent neutrophil infiltration to the infarcted area during FCI/R course. In-vitro, honokiol (0.1-10 microM) significantly diminished fMLP (N-formyl-methionyl-leucyl-phenylalanine)- or PMA (phorbol-12-myristate-13-acetate)-induced neutrophil firm adhesion, a prerequisite step behind neutrophil infiltration, and ROS production in neutrophils. Intracellular calcium overloading activates calcium-stimulated enzymes and further exaggerates FCI/R injury. Honokiol (0.1-10 microM) impeded the calcium influx induced by fMLP (a receptor agonist), AlF(4)(-) (a G-protein activator) or thapsigargin (an intracellular calcium pool releaser). Therefore, we conclude that the amelioration of FCI/R injury by honokiol can be attributed to its anti-oxidative and anti-inflammatory actions through, at least in part, limiting lipid peroxidation and reducing neutrophil activation/infiltration by interfering firm adhesion, ROS production, and calcium overloading that may be primed/activated during FCI/R injury.

Topics: Animals; Biphenyl Compounds; Brain Ischemia; Calcium; Calcium Signaling; Cell Adhesion; Cerebral Infarction; Chemotaxis, Leukocyte; Dose-Response Relationship, Drug; Infarction, Middle Cerebral Artery; Lignans; Lipid Peroxidation; Male; N-Formylmethionine Leucyl-Phenylalanine; Neuroprotective Agents; Neutrophils; Rats; Rats, Long-Evans; Reactive Oxygen Species; Reperfusion Injury; Tetradecanoylphorbol Acetate

The effects of (-)clausenamide (clau) on spatial cognitive functions and hippocampal long-term potentiation (LTP) after transient focal cerebral ischemia in rats were investigated. Four weeks after middle cerebral artery occlusion, Morris water maze tasks demonstrated that 2 h of transient forebrain ischemia resulted in a significant decrease in spatial discrimination performance. The escape latency at 4 and 5 days of acquisition trial was lower in the ischemic rats than in sham-operated rats (33.8+/-6.7 sec and 26.8+/-5 sec versus 12.2+/-4.0 sec and 10.4+/-3.6 sec), chronic treatment with clau (10 mg kg(-1) p.o. once daily) significantly improved the impairment (12.4+/-4.1 sec and 15.2+/-3.1 sec). After Morris water maze, the changes in population spike (PS) amplitude were recorded as an index of LTP in the perforant path-dentate gyrus synapses. There was no difference in PS amplitude between the sham-operated and vehicle-treated animals, whereas the fractional increase of PS 20-50 min after tetanus was significantly larger in clau-treated group. Histopathological analysis revealed that clau could protect against neuron loss in the regions of cortex and striatum. In conclusion, these data indicate a beneficial effect of clau for synaptic plasticity and cognitive function impaired by transient focal cerebral ischemia.

Topics: Action Potentials; Animals; Brain; Brain Ischemia; Cognition Disorders; Drugs, Chinese Herbal; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Lactams; Lignans; Male; Maze Learning; Nerve Degeneration; Neurons; Rats; Rats, Wistar; Recovery of Function; Reperfusion Injury; Treatment Outcome

The effects of two dibenzocyclooctene lignans on peroxidative damage of aging and ischemic rat brain were studied. Incubation of eight-month-old rat brain mitochondria and membrane suspension with Fe(2+)-cysteine resulted in the formation of malondialdehyde (MDA) and decrease of ATPase activity. Schisanhenol (Sal) (10(-4) M) completely inhibited the peroxidative damages of brain mitochondria and membrane of rats. The swelling and disintegration of brain mitochondria, as well as the reduction of brain membrane fluidity induced by Fe(2+)-cysteine were also prevented by Sal. The results of imitative experiment of ischemia and reperfusion of brain mitochondria and membrane in vitro indicated that Sal significantly impeded production of MDA and loss of ATPase activity induced by reoxygenation following anoxia. Oral administration of Sal induced increase of cytosol glutathione-peroxidase of brain in mice under the condition of reoxygenation following anoxia. The other compound schizandrin (Sin B) also has similar activity. But its potency is weaker than that of Sal. All these results indicate that Sal and Sin B have protective action against oxidative stress.

Topics: Adenosine Triphosphatases; Aging; Animals; Antioxidants; Brain; Brain Ischemia; Cyclooctanes; Drugs, Chinese Herbal; Free Radicals; Lignans; Lipid Peroxidation; Male; Mitochondrial Swelling; Polycyclic Compounds; Rats; Rats, Inbred Strains; Vitamin E

We treated four anesthetized dogs (Canis familiaris) with the platelet activating factor (PAF) receptor antagonist kadsurenone prior to 60 min of multifocal ischemia induced by air embolism, and measured neuronal recovery, blood flow and autologous 111In-labeled platelet accumulation for 4 h after ischemia. Four anesthetized animals with identical ischemia served as controls. Kadsurenone (3 mg/kg) administered 5 min prior to ischemia and continuously (1 mg/kg/hr) throughout ischemia and recovery significantly enhanced recovery of cortical somatosensory evoked response (CSER) amplitude (% of baseline) when compared to controls (27-36% vs 9-14%, p less than 0.05). We estimated platelet accumulation as 111In activity (cmp/g tissue) in the injured hemisphere minus that in the non-injured hemisphere. Kadsurenone treated animals did not exhibit significantly altered 111In-labeled platelet accumulation when compared to controls (6158 +/- 2386 vs 9979 +/- 3852, mean +/- SEM). Beneficial effects of PAF receptor blockade other than those on platelet accumulation may be involved.

Topics: Animals; Benzofurans; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Dogs; Evoked Potentials, Somatosensory; Lignans; Male; Platelet Activating Factor; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled