Alpha-Asarone Ameliorates Neurological Dysfunction of Subarachnoid Hemorrhagic Rats in Both Acute and Recovery Phases via Regulating the CaMKII-Dependent Pathways.

Early brain injury (EBI) is the leading cause of poor prognosis for patients suffering from subarachnoid hemorrhage (SAH), particularly learning and memory deficits in the repair phase. A recent report has involved calcium/calmodulin-dependent protein kinase II (CaMKII) in the pathophysiological process underlying SAH-induced EBI. Alpha-asarone (ASA), a major compound isolated from the Chinese medicinal herb Acorus tatarinowii Schott, was proven to reduce secondary brain injury by decreasing CaMKII over-phosphorylation in rats' model of intracerebral hemorrhage in our previous report. However, the effect of ASA on SAH remains unclear, and the role of CaMKII in both acute and recovery stages of SAH needs further investigation. In this work, we first established a classic SAH rat model by endovascular perforation and intraperitoneally administrated different ASA doses (10, 20, and 40 mg/kg) 2 h after successful modeling. Then, the short- and long-term neurobehavioral performances were blindly evaluated to confirm ASA's efficacy against SAH. Subsequently, we explored ASA's therapeutic mechanism in both acute and recovery stages using histopathological examination, TUNEL staining, flow cytometry, Western-blot, double-immunofluorescence staining, and transmission electron microscopy (TEM) observation. Finally, KN93, a selective CaMKII inhibitor, was applied in oxyhemoglobin-damaged HT22 cells to explore the role of CaMKII in ASA's neuroprotective effect. The results demonstrated that ASA alleviated short- and long-term neurological dysfunction, reduced mortality and seizure rate within 24 h, and prolonged 14-day survival in SAH rats. Histopathological examination showed a reduction of neuronal damage and a restoration of the hippocampal structure after ASA treatment in both acute and recovery phases of SAH. In the acute stage, the Western-blot and flow cytometer analyses showed that ASA restored E/I balance, reduced calcium overload and CaMKII phosphorylation, and inhibited mitochondrion-involved apoptosis, thus preventing neuronal damage and apoptosis underlying EBI post-SAH. In the recovery stage, the TEM observation, double-immunofluorescence staining, and Western-blot analyses indicated that ASA increased the numbers of synapses and enhanced synaptic plasticity in the ipsilateral hippocampi, probably by promoting NR2B/CaMKII interaction and activating subsequent CREB/BDNF/TrkB signaling pathways. Furthermore, KN93 notably reversed ASA's neuroprotective effect on oxyhemoglobin-damaged HT22 cells, confirming CaMKII a potential target for ASA's efficacy against SAH. Our study confirmed for the first time that ASA ameliorated the SAH rats' neurobehavioral deterioration, possibly via modulating CaMKII-involved pathways. These findings provided a promising candidate for the clinical treatment of SAH and shed light on future drug discovery against SAH.

Purple perilla frutescens extracts containing α-asarone inhibit inflammatory atheroma formation and promote hepatic HDL cholesterol uptake in dyslipidemic apoE-deficient mice.

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

Alpha-asarone ameliorates neurological deterioration of intracerebral hemorrhagic rats by alleviating secondary brain injury via anti-excitotoxicity pathways.

BACKGROUND: Secondary brain injury (SBI) has been confirmed as a leading cause for the poor prognosis of patients suffering from intracerebral hemorrhage (ICH). SBI co-exists in ischemia and hemorrhagic stroke. Neuro-excitotoxicity is considered the initiating factor of ICH-induced SBI. Our previous research has revealed alpha-asarone (ASA)'s efficacy against cerebral ischemia-reperfusion stroke by mitigating neuro-excitotoxicity. It is not yet known if ASA exhibit neuroprotection against ICH. PURPOSE: This work aimed to investigate ASA's therapeutic effects and potential mechanisms of action against ICH in a classic rat model induced by collagenase Ⅶ injection. METHODS: An in vivo ICH model of Sprague-Dawley rats was established by collagenase Ⅶ injection. We administrated different ASA doses (10, 20, or 40 mg/kg, i.p.) at 2 h post-ICH. Then, rats' short- and long-term neurobehavioral function, bodyweight change, and learning and memory ability were blindly evaluated. Histological, Nissl, and flow cytometry were applied to assess the neuronal damage post-ICH. The wet/dry method and Evans blue extravasation estimated brain edema and blood-brain barrier function. Pathway-related proteins were investigated by immunofluorescence staining, enzyme-linked immunosorbent assay, and Western-blot analysis. RESULTS: The results demonstrated that ASA ameliorated neurological deterioration, bodyweight loss, and learning and memory ability of ICH rats. Histological, Nissl, and flow cytometry analyses showed that ASA reduced neuronal damage and apoptosis post-ICH. Besides, ASA probably mitigated brain edema and blood-brain barrier dysfunction via inhibiting astrocyte activation and consequent pro-inflammatory response. The mechanism investigation attributed ASA's efficacy to the following aspects: 1) promoting sodium ion excretion, thus blocking excitatory signal transduction along the axon; 2) preventing glutamate-involved pathways, i.e., decrease of N-methyl-d-aspartic acid receptor subunit 2B, increase of glutamate transporter-1, and alleviation of calcium-related cascades, mitochondrion-associated apoptosis, and neuronal autophagy; 3) enhancing the expression of GABAARs, thus abating neuronal excitotoxicity. CONCLUSION: Our study first confirmed the effect of ASA on ameliorating the neurobehavioral deterioration of ICH rats, possibly via alleviation of glutamate-involved neuro-excitotoxicity, i.e., calcium cascades, mitochondrion-involved apoptosis, neuronal autophagy, and astrocyte-related inflammation. These findings not only provided a promising drug candidate for clinical treatment of ICH but also shed light on the future drug discovery against ICH.

Neuroprotective Effect of Alpha-asarone on the Rats Model of Cerebral Ischemia-Reperfusion Stroke via Ameliorating Glial Activation and Autophagy.

Alpha-asarone, a major active component isolated from Acorus gramineus, can affect brain functions and behaviors by multiple mechanisms. However, the effect of alpha-asarone on cerebral ischemia-reperfusion (CIR) stroke has not been reported. The present study aimed to investigate the neuroprotective effect of alpha-asarone and the involved mechanisms against CIR stroke. Rats were subjected to middle cerebral occlusion (MCAO) for 2 h. Then the drug or drug-free vehicle was intravenously injected to corresponding groups. After reperfusion for 24 h, the infarct volume was evaluated by Triphenyl Tetrazolium Chloride (TTC) staining. The neurofunctional recovery and post-stroke epilepsy were evaluated. Nissl and Hematoxylin-Eosin (H&E) staining were used for histological observation. We investigated the protective mechanism of alpha-asarone against the stroke. The results showed that alpha-asarone exhibited a desirable neuroprotective effect, manifested as reducing infarct volume and post-stroke epilepsy and improving neurological function. Histological and flow cytometry analysis revealed that alpha-asarone treatment alleviated cell injury and apoptosis in vivo and in vitro. Furthermore, alpha-asarone decreased GFAP, Iba-1, and LC3II/LC3I expression and increased the expression of p62. These results suggested that alpha-asarone attenuated the CIR stroke injury via ameliorating glial activation and autophagy.

Alpha-asarone Improves Cognitive Function of APP/PS1 Mice and Reducing Aß42, P-tau and Neuroinflammation, and Promoting Neuron Survival in the Hippocampus.

Alzheimer's disease (AD) is a progressive neurodegenerative disease most often characterized by memory impairment and cognitive decline. Alpha-asarone has been reported to have the potential to treat AD. Our previous studies have found that alpha-asarone improves aged rats' cognitive function by alleviating neuronal excitotoxicity via type A gamma-aminobutyric acid (GABA) receptors. GABA level's change, neuroinflammation, and dysfunctional autophagy are found to be associated with AD. However, the effect of alpha-asarone on cognitive function of APP/PS1 transgenic mice and its underlying mechanism in terms of aggregation of amyloid-ß42 (Aß42) and phosphorylated tau (p-tau), glutamic acid decarboxylase (GAD) level, neuroinflammation, and autophagy are unclear. Accordingly, we attempted to explore whether alpha-asarone improves AD mice's cognitive function and alleviates pathological symptoms by regulating GAD level, inhibiting neuroinflammation, or restore autophagy. We found that alpha-asarone enhanced spatial learning memory and decreased Aß42 and p-tau levels without influencing the GAD level in APP/PS1 transgenic mice. Also, it decreased the GFAP expression and reduced pro-inflammatory cytokines levels, thus alleviating neuroinflammation. Furthermore, alpha-asarone decreased the excess number of autophagosomes and promoted hippocampal neurons' survival. In conclusion, the results confirmed the therapeutic effect of alpha-asarone on AD-related astrogliosis, dysfunctional autophagy, and neuronal damage, which indicates its great potential to treat AD.

[Effects of acorus tatarinowii Schott and alpha asarone on free radicals and nNOS/NO in hippocampus of rats with fatigue movement].

OBJECTIVE: To study the effects of acorus tatarinowii Schott and its active ingredient-alpha-asarone on learning and memory, free radical metabolism and nNOS/NO signal in hippocampus of rats with fatigue movement. METHODS: Eighty SD male rats were randomly divided into eight groups: control group(A), exercise group(B), exercise + alpha-asarone low, middle and high dose treatment group (C, D, E), exercise + acorus tatarinowii Schott low, middle and high dose treatment group (F, G, H),with ten rats in each group. The rats in group C, D and E were administered with alpha-asarone at the doses of 0.10, 0.50 and 1.00 mg.kg-1.WT-1 by ig. The rats in group F, G and H were administered with the extracts of Acorus tatarinowii Schott of at the doses of 0.12, 1.20 and 4.80 g.kg-1.WT-1 by ig. Learning and memory of rats were tested by the method of water maze experiment, and the activities of SOD and NOS, the contents of MDA were detected by the biochemical methods, and the expression levels of nNOS protein in hippocampus of rats were tested by the method of Western blot in at the end of the experiment. RESULTS: The escape latency and MDA content in hippocampus of rats in groups E and H were lower than those in groups B, C, D, F and G and the numbers of Plateau crossing, SOD and NOS activities and the expression levels of nNOS protein in hippocampus of rats were higher than those in groups B, C, D, F and G(P＜0.01). The activities of SOD in hippocampus of rats in groups A, E and H were A＞E＞H, whereas the contents of MDA were opposite (P＜0.01); the activities of NOS and the expression levels of nNOS protein in hippocampus of group E were lower than those of groups A and H (P＜0.01 or P＜0.05), but there was no significant difference between groups A and H (P＞0.05). There were no significant difference in escape latency and numbers of crossing platform among groups A, E and H (P＞0.05). CONCLUSION: Acorus tatarinowii Schott and alpha-asarone can significantly improve learning and memory of rats with fatigue movement. The mechanism is related to reclaiming the imbalance of free radical metabolism and up-regulating nNOS/NO signal in hippocampus of the rats.

Alpha-asarone attenuates depression-like behavior in nicotine-withdrawn mice: Evidence for the modulation of hippocampal pCREB levels during nicotine-withdrawal.

In the present study, the effect α-asarone on nicotine withdrawal-induced depression-like behavior in mice was investigated. In this study, mice were exposed to drinking water or nicotine solution (10-200µg/ml) as a source of drinking for forty days. During this period, daily fluid consumption, food intake and body weight were recorded. The serum cotinine level was estimated before nicotine withdrawal. Naïve mice or nicotine-withdrawn mice were treated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) for eight consecutive days and the forced swim test (FST) or locomotor activity test was conducted. In addition, the effect of α-asarone or bupropion on the hippocampal pCREB, CREB and BDNF levels during nicotine-withdrawal were measured. Results indicated that α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment did not significantly alter the immobility time in the FST or spontaneous locomotor activity in naïve mice. However, the immobility time of nicotine-withdrawn mice was significantly attenuated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment in the FST. Besides, α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment significantly attenuated the hippocampal pCREB levels in nicotine-withdrawn mice. Overall, the present results indicate that α-asarone treatment attenuated the depression-like behavior through the modulation of hippocampal pCREB levels during nicotine-withdrawal in mice.

Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice.

Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (α)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with α-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of α-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, α-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of α-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity.

Systemic delivery of alpha-asarone with Kolliphor HS 15 improves its safety and therapeutic effect on asthma.

The commercially available alpha-asarone injections (CA-ARE) were frequently found to cause severe anaphylactic reactions by the solubilizer contained in the formulation such as polysorbate 80 and propylene glycol. This study aimed to develop a new ARE injection using Kolliphor HS 15 as solubilizing agent (HS 15-ARE) by the dissolution method to resolve its poor solubility problem and reduce the anaphylaxis of CA-AREs caused by Polysorbate 80. The HS 15-ARE micelle showed a homogeneous round shape with the mean particle size of around 13.73 ± 0.02 nm, polydisperse index (PDI) of 0.19 ± 0.01 and solubilizing efficiency of 95.7% ± 2.4%. In vitro and in vivo studies showed that HS 15-ARE is a stable injection presenting the same pharmacokinetic profile with CA-ARE. Moreover, improved therapeutic effect was observed for HS 15-ARE in treating asthma compared to CA-ARE (p < 0.05) with no anaphylactic reactions observed. These results demonstrate that the new formulation of ARE (HS 15-ARE) has a great potential for replacing CA-AREs injections.

The involvement of neuronal nitric oxide synthase in antiepileptic action of alpha-asarone on pentylenetetrazol molding rats.

The aim of the present study was to research the role of nitric oxide (NO) as a mediator of alpha (α)-asarone effect at the pentylenetetrazol (PTZ)-induced epileptiform discharge in rat. α-Asarone that was injected intraperitoneally twenty minutes before PTZ injection suppressed the clonic discharge effectively and the significant actions lasted for 30 min with no change of clonic amplitude. Administration of α-asarone did not influence interictal discharge. Four kinds of NO regulators were administered, including non-selective NG-nitro-L-arginine methyl ester (L-NAME), selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG) and NO substrate, L-arginine (ARG) and their influence on the actions of α-asarone were studied, and all of the regulators were administered fifteen minutes before α-asarone injection. L-NAME and 7-NI reversed the anticlonic activity of α-asarone, and a significant increase of clonic activity was induced by L-NAME later in L-NAME +.α-asarone + PTZ group. There were no significant differences between AG + α-asarone + PTZ and α-asarone + PTZ group. L-ARG played a dual role in this study. It aggravated clonic discharge in the early stage but relieved interictal discharge in the late stage compared with PTZ group alone, and the beneficial effect of α-asarone was also reversed. All the above results suggest that nNOS/NO pathway mediates the anticonvulsant effect of α-asarone, and NO played a biphasic role in PTZ modeling process, while iNOS was unrelated to the inhibition effect of α-asarone on PTZ induced epileptiform activity.

alpha-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation

alpha-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of alpha-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of alpha-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. alpha-Asarone significantly reduced TNF-alpha and IL-1beta mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of alpha-asarone treatment. alpha-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. alpha-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of alpha-asarone treatment. In the Morris water maze test, alpha-asarone significantly prolonged the swimming time spent in the target and peri-target zones. alpha-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by alpha-asarone may be one of the mechanisms for the alpha-asarone-mediated ameliorating effect on memory deficits.

alpha-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation

alpha-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of alpha-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of alpha-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. alpha-Asarone significantly reduced TNF-alpha and IL-1beta mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of alpha-asarone treatment. alpha-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. alpha-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of alpha-asarone treatment. In the Morris water maze test, alpha-asarone significantly prolonged the swimming time spent in the target and peri-target zones. alpha-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by alpha-asarone may be one of the mechanisms for the alpha-asarone-mediated ameliorating effect on memory deficits.

Alpha-Asarone, a Major Component of Acorus gramineus, Attenuates Corticosterone-Induced Anxiety-Like Behaviours via Modulating TrkB Signaling Process

We investigated the anxiolytic-like activity of alpha-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

Synthesis and antifeedant activity of novel alpha-asarone derivatives against stored-product pests.

BACKGROUND: Alpha-asarone (2,4,5-trimethoxypropenylbenzene) derivatives represent a new series of compounds that possess good antifeedant activity against different stored-product pests. RESULTS: A total of 23 novel alpha-asarone derivatives were synthesised and identified by (1) H NMR, (13) C NMR and IR, and their feeding deterrent activities were tested against Sitophilus granarius L., Trogoderma granarium Ev. and Tribolium confusum Duv. Ten compounds showed strong antifeedant activities. CONCLUSION: Some of the title compounds displayed very good and broad-spectrum activities against adult and larval Coleoptera. The results indicate that the presence of a double bond in the side chain and three methoxy groups is important for antifeedant activity.

Experimental study on the antiepileptic properties of alpha-asarone in different epilepsy models / 中国药理学通报

Aim To investigate the antiepileptic activity of alpha-asarone in three epilepsy models.Methods The MES mice,MST mice and Lithium-pilocarpine rats were divided randomly and respectively into groups each containing 20 animals(?-asarone groups,AED groups and normal control group).Different doses of alpha-asarone were administered to mice/rats in advance in alpha-asarone treated groups,one group received only saline,while the other groups received antiepileptic drug as a reference standard,2 times per day for 28 days.The seizure severity score,seizure latency and total number of animals with seizures were noted to observe whether alpha-asarone had anticonvulsant effect or not in three epilepsy models.Results Alpha-asarone possessed excellent anticonvulsant effect in MES and MST and lithium-pilocarpine models. It significantly decreased the seizure incidence 40%~100% in the MES models and 50%~90% in MST models,and 40%~80% in the Lithium-pilocarpine model. It significantly prolonged the seizure latency 70~180 s in MST mice and 4~15 min in Lithium-pilocarpine rats;It significantly reduced the seizure severity scores 1.96 in Lithium-pilocarpine rats.Conclusions Alpha-asarone had a positive antiepileptic activity.