Thrombospondin-2 promotes the proliferation and migration of glioma cells and contributes to the progression of glioma.

BACKGROUND: Gliomas, especially high-grade gliomas, are highly malignant with a poor prognosis. Although existing treatments have improved the survival rate of patients with glioma, the recurrence and mortality rates are still not ideal. The molecular mechanisms involved in the occurrence and development of glioma are still poorly understood. We previously reported that thrombospondin-2 (TSP2) expression was increased in tumor specimens from rat models, promoting excitatory synapse formation. However, little is known about the effect of TSP2 on the biological characteristics of glioma. METHODS: Glioma and cerebral cortex tissues were collected from 33 patients, and the expression of TSP2 in them was analyzed. Next, the proliferation and migration of TSP2 on glioma cells were analyzed in vitro. At last, a glioma transplantation model was constructed to explore the growth of TSP2 on glioma in vivo. RESULTS: The expression of TSP2 in surgical glioma specimens was increased compared to that in the normal cortex. Interestingly, the TSP2 protein level was higher in high-grade glioma (HGG, World Health Organization (WHO) grades 3-4) than in low-grade glioma (LGG, WHO grades 1-2) tissues. Exogenous addition of the TSP2 protein at an appropriate concentration promoted the migration of glioma cells but did not significantly affect their proliferation. Surprisingly, overexpression of TSP2 promoted both the migration and proliferation of cultured glioma cells. Moreover, in vivo experimental data implied that overexpression of TSP2 in C6 cells promoted the malignant growth of gliomas, while knockout of TSP2 slowed glioma growth. CONCLUSIONS: TSP2 promotes the migration and proliferation of glioma cells, which may provide new ideas for blocking glioma progression.

Glioma-Derived TSP2 Promotes Excitatory Synapse Formation and Results in Hyperexcitability in the Peritumoral Cortex of Glioma.

Seizures are common in patients with glioma, especially low-grade glioma (LGG). However, the epileptogenic mechanisms are poorly understood. Recent evidence has indicated that abnormal excitatory synaptogenesis plays an important role in epileptogenesis. The thrombospondin (TSP) family is a key regulator of synaptogenesis. Thus, this study aimed to elucidate the role of TSP2 in epileptogenesis in glioma-related epilepsy. The expression of TSP2 was increased in tumor tissue specimens from LGG patients, and this increase may have contributed to an increase in the density of spines and excitatory synapses in the peritumoral area. A glioma cell-implanted rat model was established by stereotactic implantation of wild-type TSP2-expressing, TSP2-overexpressing or TSP2-knockout C6 cells into the neocortex. Similarly, an increase in the density of excitatory synapses was also observed in the peritumoral area of the implanted tumor. In addition, epileptiform discharges occurred in the peritumoral cortex and were positively correlated with the TSP2 level in glioma tissues. Moreover, α2δ1/Rac1 signaling was enhanced in the peritumoral region, and treatment with the α2δ1 antagonist gabapentin inhibited epileptiform discharges in the peritumoral cortex. In conclusion, glioma-derived TSP2 promotes excitatory synapse formation, probably via the α2δ1/Rac1 signaling pathway, resulting in hyperexcitability in the peritumoral cortical networks, which may provide new insight into the epileptogenic mechanisms underlying glioma-related epilepsy.

NFAT5 protects astrocytes against oxygen-glucose-serum deprivation/restoration damage via the SIRT1/Nrf2 pathway.

Nuclear factor of activated T cells (NFAT) is a multifunctional cytokine family. NFAT5 was recently reported to be involved in many neuronal functions, but its specific function remains unclear. In this study, our aim is to investigate whether NFAT5 overexpression can protect astrocytes against oxygen-glucose-serum deprivation/restoration (OGSD/R) damage. In vivo, rats were subjected to ischemia-reperfusion injury, resulting in increased water content, infarct volume, and expression of NFAT5 protein in rat spinal cord. After primary culture for spinal cord astrocytes, the in vitro OGSD/R model was established. The results of the CCK8 assay and flow cytometry showed that, in the OGSD/R group, astrocyte cell viability was downregulated, but astrocyte apoptosis increased. Caspase 3 activity increased as well. Levels of NFAT5, as detected by real-time quantitative PCR and western blot, decreased under OGSD/R, as did SIRT1. Commercial kits for activity assays were used to show that OGSD/R inhibited SIRT1 activation but accelerated SOD activation after OGSD/R. Next, pcDNA-NFAT5 or NFAT5 siRNA was transfected into astrocytes. Overexpression of NFAT5 not only promoted the survival of the astrocytes and SIRT1 activation under OGSD/R but also inhibited cell apoptosis and SOD activation. Moreover, overexpression of NFAT5 apparently diminished histone acetylation and promoted the nuclear transport of Nrf2. Our results show that NFAT5 protects spinal astrocytes in a manner that depends on activation of the SIRT1/Nrf2 pathway. These findings present a novel potential molecular mechanism for NFAT5 therapy in the context of spinal cord injury.

Impact of Heat Shock Protein A 12B Overexpression on Spinal Astrocyte Survival Against Oxygen-Glucose-Serum Deprivation/Restoration in Primary Cultured Astrocytes.

Heat shock protein A 12B (HSPA12B) is a newly discovered member of the heat shock protein 70 family. Preclinical evidence indicates that HSPA12B helps protect the brain from ischemic injury, although its specific function remains unclear. The aim of this study is to investigate whether HSPA12B overexpression can protect astrocytes from oxygen-glucose-serum deprivation/restoration (OGD/R) injury. We analyzed the effects of HSPA12B overexpression on spinal cord ischemia-reperfusion injury and spinal astrocyte survival. After ischemia-reperfusion injury, we found that HSPA12B overexpression decreased spinal cord water content and infarct volume. MTT assay showed that HSPA12B overexpression increased astrocyte survival after OGD/R treatment. Flow cytometry results showed a marked inhibition of OGD/R-induced astrocyte apoptosis. Western blot assay showed that HSPA12B overexpression significantly increased regulatory protein B-cell lymphocyte 2 (Bcl-2) levels, whereas it decreased expression of the Bax protein, which forms a heterodimer with Bcl-2. Measurements of the level of activation of caspase-3 by Caspase-Glo®3/7 Assay kit showed that HSPA12B overexpression markedly inhibited caspase-3 activation. Notably, we demonstrated that the effects of HSPA12B on spinal astrocyte survival depended on activation of the PI3K/Akt signal pathway. These findings indicate that HSPA12B protects against spinal cord ischemia-reperfusion injury and may represent a potential treatment target.

microRNA-7 Protects Against 1-Methyl-4-Phenylpyridinium Iodide-Induced Cell Apoptosis in SH-SY5Y Cells by Directly Targeting Krüpple-Like Factor 4.

This study intended to investigate the role and underling mechanism of microRNA-7 (miR-7) on neuronal death in Parkinson's disease (PD). Human neuroblastoma cell line SH-SY5Y was employed and 1-methyl-4-phenylpyridinium iodide [MPP(+)] was used to generate PD model in vitro. Furthermore, an upregulation of miR-7 was performed in SH-SY5Y by transfection with miR-7 mimics. Cell viability and cell apoptosis were determined. Moreover, the target and the mechanism of miR-7 in MPP(+)-induced cell death were also investigated. The upregulation of miR-7 promoted cell viability and suppressed cell apoptosis in MPP(+)-treated SH-SY5Y cells. Furthermore, miR-7 could directly bind to the 3'-untranslated region of Krüppel-like factor 4 (KLF4, positions 574-580). Moreover, knockdown of KLF4 by the specific siRNA inhibited SH-SY5Y apoptosis under MPP(+) treatment. In addition, KLF4 overexpression apparently attenuated the protective effect of miR-7 in MPP(+)-induced SH-SY5Y apoptosis. This study indicated that miR-7 protects from MPP(+)-induced cell apoptosis in SH-SY5Y by directly targeting KLF4.

Genetic predisposition of stroke: understanding the evolving landscape through meta-analysis.

Stroke, either ischemic or hemorrhagic, is the leading cause of death and morbidity worldwide. Identifying the risk factors is a prerequisite step for stroke prevention and treatment. It is believed that a major portion of the currently unidentified risk factors is of genetic origin. Consistent with this idea, numerous potential risk alleles for stroke have been reported, however, the genetic evidence so far is not conclusive. The major goal of this review is to update the current knowledge about the genetic predisposition to the common multifactorial stroke, and to provide a bird's-eye view of this fast moving field. We selectively review and meta-analyze the related English literatures in public domain (PubMed) from 2000 onward, including the original reports and meta-analyses, to evaluate the genetic risk factors of common multifactorial stroke. The results indicated that we reviewed and meta-analyzed original reports and existing meta-analyses that studied the genetic predisposition to the common multifactorial stroke. Some original reports and meta-analyses were specific for ischemic stroke and others were for hemorrhagic stroke only. We also evaluated the major evolving issues in this field and discussed the future directions. In conclusion, strong evidences suggest that genetic risk factors contribute to common multifactorial stroke, and many genetic risk genes have been implicated in the literatures. However, not a single risk allele has been conclusively approved.

Multicenter study on adult growth hormone level in postoperative pituitary tumor patients.

The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications.

Aerobic exercise for Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although some trials assessed the effectiveness of aerobic exercise for Parkinson's disease (PD), the role of aerobic exercise in the management of PD remained controversial. OBJECTIVE: The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD. METHODS: Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I2 statistic. RESULTS: 18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, -0.57; 95% CI -0.94 to -0.19; p = 0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p = 0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI -0.23 to 0.46; p = 0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD. CONCLUSION: Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings.

Analyzing time-series microarray data reveals key genes in spinal cord injury.

Although many scholars have utilized high-throughput microarrays to delineate gene expression patterns after spinal cord injury (SCI), no study has evaluated gene changes in raphe magnus (RM) and somatomotor cortex (SMTC), two areas in brain primarily affected by SCI. In present study, we aimed to analyze the differentially expressed genes (DEGs) of RM and SMTC between SCI model and sham injured control at 4, 24 h, 7, 14, 28 days, and 3 months using microarray dataset GSE2270 downloaded from gene expression omnibus and unpaired significance analysis of microarray method. Protein-protein interaction (PPI) network was constructed for DEGs at crucial time points and significant biological functions were enriched using DAVID. The results indicated that more DEGs were identified at 14 days in RM and at 4 h/3 months in SMTC after SCI. In the PPI network for DEGs at 14 days in RM, interleukin 6, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), FBJ murine osteosarcoma viral oncogene homolog (FOS), tumor necrosis factor, and nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) were the top 5 hub genes; In the PPI network for DEGs at 3 months in SMTC, the top 5 hub genes were ubiquitin B, Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), FOS, Janus kinase 2 and vascular endothelial growth factor A. Hedgehog and Wnt signaling pathways were the top 2 significant pathways in RM. These hub DEGs and pathways may be underlying therapeutic targets for SCI.

Emodin inhibits inducible nitric oxide synthase in a rat model of craniocerebral explosive injury.

To investigate the effects of emodin on blast-induced traumatic brain injury (bTBI) in a rat model. Eighty rats were randomly divided into 2 groups (the control group and the emodin-treated group; N = 40 per group) and were used to establish the model of blast-induced traumatic brain injury. Ten minutes after the explosion, an isotonic saline solution (10 mg/kg) or emodin (10 mg/kg) were administered via an intraperitoneal injection to the control group and the emodin-treated group, respectively. At each time point (pre-explosion, 2, 6, 12, 24 h after explosion), 2 rats were used for the pathological assessment and 6 rats were used for the biochemical assessment. The concentration of nitric oxide (NO) and the expression and activity of inducible nitric oxide synthase (iNOS) were measured at each time point by spectrophotometry and western blot analysis. Light and electron microscopy showed that the brain damage in the emodin-treated group was less serious than that observed in the control group. The concentration of NO in the emodin-treated group was lower compared with the control group (p < 0.05). Western blot analysis showed that protein expression in the emodin-treated group was lower than the control group (p < 0.05). Emodin can alleviate brain damage after bTBI by inhibiting iNOS. These findings suggest that emodin has a protective effect against bTBI. One possible mechanism may occur by inhibiting the expression and activity of iNOS and consequently decreasing the concentration of NO.

Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma.

Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain (P < .001), whereas CREB-1 messenger RNA expression was significantly elevated in the tumors (P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade (P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score (P = .03), and high CREB-1 expression correlated positively with mean tumor diameter (P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time.

Anti-apoptotic and anti-oxidative roles of quercetin after traumatic brain injury.

Experimental studies have demonstrated significant secondary damage (including cell apoptosis, blood-brain barrier disruption, inflammatory responses, excitotoxic damage, and free radical production) after traumatic brain injury (TBI). Quercetin is a natural flavonoid found in high quantities in fruits and vegetables, and may be a potential antioxidant and free radical scavenger. The purpose of this study was to determine the effects of quercetin on TBI-induced upregulation of oxidative stress, inflammation, and apoptosis in adult Sprague-Dawley rats. Animals were subjected to Feeney's weight-drop injury, thus inducing the parietal contusion brain injury model. Quercetin was administered (30 mg/kg intraperitoneal injection) 0, 24, 48, and 72 h after TBI. Quercetin reduced cognitive deficits, the number of TUNEL- and ED-1-positive cells, the protein expressions of Bax and cleaved-caspase-3 proteins, and the levels of TBARS and proinflammatory cytokines, and increased the activity of antioxidant enzymes (GSH-Px, SOD, and CAT) at 1 week after TBI. Our results suggest that in TBI rats, quercetin improves cognitive function owing to its neuroprotective action via the inhibition of oxidative stress, leading to a reduced inflammatory response, thereby reducing neuronal death.

Epileptiform Discharges and Frontal Paroxysmal EEG Abnormality Act as Predictive Marker for Subsequent Epilepsy in Children With Complex Febrile Seizures.

Using electroencephalography (EEG) for diagnosing subsequent epilepsy in children after febrile seizure (FS) is not common. The present study investigates the relationship between epileptiform discharges and subsequent epilepsy, and looks for the predictive marker for this disorder. A total of 378 children with complex FS and whose EEG showed epileptiform discharges or normal EEG were included. Development of FS was compared between those with epileptiform discharges and those with normal EEG. Risk factors were analyzed using multivariate logistic regression to clarify their effects on subsequent epilepsy. The association between generalized or focal EEG localization, and between frontal epileptiform discharges and subsequent epilepsy, were analyzed. Among 378 patients with complex FS, 51 showed epileptiform discharges. History of epilepsy, frontal seizure, number of FS, and prolonged seizure were the risk factors for epileptiform discharge. Subsequent epilepsy was significantly frequent in patients with more than 2 risk factors (odds ratio [OR] = 17; 95% confidence interval [CI] = 4.1-29.6). Prolonged seizure (OR = 4.98; 95% CI = 1.63-13.29), FS number (OR = 2.96; 95% CI = 1.23-10.51), and family history of epilepsy (OR = 2.67; 95% CI = 1.05-7.63) were significantly correlated with subsequent epilepsy. Of 9 patients with paroxysms in the frontal region, 8 (88.9%) developed epilepsy. There was concordance between frontal epileptiform discharges and subsequent epilepsy (κ = .901). In conclusion, epileptiform discharges are risk factors for subsequent epilepsy. Frontal paroxysmal EEG is a marker for subsequent epilepsy.

Comparison of the safety and efficacy of propofol with midazolam for sedation of patients with severe traumatic brain injury: a meta-analysis.

OBJECTIVE: To perform a meta-analysis to compare the safety and efficacy of propofol with midazolam for sedation of patients with severe traumatic brain injury. MATERIALS AND METHODS: Studies were included in the meta-analysis if they met the following criteria: randomized controlled trial of sedative-hypnotic agents including propofol and midazolam; patients had severe traumatic brain injury; the primary outcome was the Glasgow Outcome Scale score; secondary outcomes included mortality, therapeutic failure, intracranial pressure, and cerebral perfusion pressure. The data were analyzed using software for meta-analysis. RESULTS: Seven relevant studies were identified. Three of these studies were excluded: one was a single-arm study, one compared morphine and propofol, and for one the full text article could not be obtained. The remaining 4 studies were included in the meta-analysis. The results of the meta-analysis showed that propofol and midazolam have similar effects on the Glasgow Outcome Scale score, mortality, intracranial pressure, and cerebral perfusion pressure. CONCLUSION: Our meta-analysis of 4 studies showed that there are no important differences between propofol and midazolam when administered to provide sedation for patients with severe traumatic brain injury. Further randomized, controlled trials comparing propofol with midazolam for sedation of such patients are needed.

Protein-protein interaction network analysis and gene set enrichment analysis in epilepsy patients with brain cancer.

Many patients with brain cancer experience seizures or epilepsy and tumor-associated epilepsy (TAE) significantly decreases their quality of life. This study aimed to achieve a better understanding of the mechanisms of TAE. The differentially expressed genes (DEG) between epilepsy patients with or without brain tumor were firstly screened using the Linear Models for Microarray Data package using GSE4290 datasets from the USA National Center for Biotechnology Information Gene Expression Omnibus database. Then the protein-protein interaction (PPI) network, using data from the Human Protein Reference Database and the Biological General Repository for Interaction Datasets, was constructed. For further analysis, the PPI network structure and clusters in this PPI network were identified by ClusterOne. Meanwhile, gene set enrichment analysis was performed to illuminate the biological pathways and processes which generally affect patients with TAE. A total of 5113 DEG were identified and a PPI network, which contained 114 DEG and 21 normal genes, was established. Proteins, which mainly belonged to the mini chromosome maintenance and collagen families, were discovered to be enriched in the three identified clusters in the PPI network. Finally, several biological pathways (including cell cycle, DNA replication and transforming growth factor ß1 signaling pathways) and processes (such as nucleocytoplasmic transport, nuclear transport and regulation of phosphorylation) were identified. Proteins in these three clusters may become new targets for TAE treatment. Our results provide some potential underlying biomarkers for understanding the pathogenesis of epilepsy in patients with brain tumor.

Overexpression of MACC1 protein and its clinical implications in patients with glioma.

Metastasis associated in colon cancer 1 (MACC1) has been regarded as a novel potential therapeutic target for multiple cancers. However, the impact of MACC1 in glioma remains unclear. The aim of this study was to analyze the correlation of MACC1 expression with the clinicopathological features of glioma. MACC1 mRNA and protein expression levels in human glioma tissues were detected by quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. MACC1 mRNA and protein expression were both significantly higher in glioma tissues than in corresponding noncancerous brain tissues (both P < 0.001). In addition, statistical analysis suggested that high MACC1 expression was significantly correlated with advanced pathological grade (P = 0.004) and that patients with high expression of MACC1 protein exhibited a poorer prognosis than those with low MACC1 expression. Furthermore, Cox multivariate analysis showed that MACC1 overexpression was an independent prognostic factor for predicting the overall survival of glioma patients. In conclusion, expression of MACC1 in glioma could be adopted as a candidate biomarker for the diagnosis of clinical stage and for assessing prognosis, indicating for the first time that MACC1 may play an important role in the tumor development and progression in glioma. MACC1 might be considered as a novel therapeutic target against this cancer.

Endogenous subventricular zone neural progenitors contribute to the formation and hyperexcitability of experimental model of focal microgyria.

Microgyria is associated with epilepsy and due to developmental disruption of neuronal migration. However, the role of endogenous subventricular zone-derived neural progenitors (SDNPs) in formation and hyperexcitability has not been fully elucidated. Here, we establish a neonatal cortex freeze-lesion (FL) model, which was considered as a model for focal microgyria, and simultaneously label SDNPs by CM-DiI. Morphological investigation showed that SDNPs migrated into FL and differentiated into neuronal and glia cell types, suggesting the involvement of endogenous SDNPs in the formation of FL-induced microgyria. Patch-clamp recordings in CM-DiI positive (CM-DiI(+)) pyramidal neurons within FL indicated an increase in frequency of spontaneous action potentials, while the resting membrane potential did not differ from the controls. We also found that spontaneous excitatory postsynaptic currents (EPSCs) increased in frequency but not in amplitude compared with controls. The evoked EPSCs showed a significant increase of 10-90% in rise time and decay time in the CM-DiI(+) neurons. Moreover, paired-pulse facilitation was dramatically larger in CM-DiI(+) pyramidal neurons. Western blotting data showed that AMPA and NMDA receptors were increased to some extent in the FL cortex compared with controls, and the NMDA/AMPA ratio of eEPSCs at CM-DiI(+) pyramidal neurons was significantly increased. Taken together, our findings provide novel evidence for the contribution of endogenous SDNPs in the formation and epileptogenicity of FL-induced focal microgyria.

Anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats.

This study was designed to evaluate the anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats. In the present study, anticonvulsant activities of paederosidic acid were evaluated by maximal electroshock and pentylenetetrazole-induced seizures in male mice. Then, pentobarbital sodium-induced sleeping time and locomotor activity tests in mice were used to evaluate the sedative effects of paederosidic acid. Finally, the mechanism of paederosidic acid was explored by evaluating the contents of Glu and GABA in the brain, and Western blot was used to measure GAD65 expression in the mouse brain. Paederosidic acid (5, 10, 20, and 40 mg/kg, ip) had significant anticonvulsant and sedative effects. Moreover, paederosidic acid increased brain gamma-aminobutyric acid and decreased glutamic acid in the brain, and it up-regulated expressions of GAD 65. In conclusion, our results suggest that paederosidic acid may be a promising future therapeutic agent for treatment of epilepsy.