alpha-asarone and Epilepsy

In the present study, we compared the antiepileptic effects of α-asarone derivatives to explore their structure-activity relationships using the PTZ-induced seizure model. Our research revealed that electron-donating methoxy groups in the 3,4,5-position on phenyl ring increased antiepileptic potency but the placement of other groups at different positions decreased activity. Besides, in allyl moiety, the optimal activity was reached with either an allyl or a 1-butenyl group in conjugation with the benzene ring. The compounds 5 and 19 exerted better neuroprotective effects against epilepsy in vitro (cell) and in vivo (mouse) models. This study provides valuable data for further exploration and application of these compounds as potential anti-seizure medicines.

Topics: Allylbenzene Derivatives; Animals; Anisoles; Anticonvulsants; Cells, Cultured; Disease Models, Animal; Epilepsy; Male; Mice; Neuroprotective Agents; Rats, Sprague-Dawley; Structure-Activity Relationship

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.

Topics: Action Potentials; Allylbenzene Derivatives; Animals; Anisoles; Brain; Convulsants; Dose-Response Relationship, Drug; Drug Interactions; Epilepsy; Female; Nitric Oxide; Nitric Oxide Synthase Type I; Pentylenetetrazole; Rats; Rats, Wistar; Treatment Outcome

Alpha (α)-asarone is a major effective compound isolated from the Chinese medicinal herb Acorus gramineus, which is widely used in clinical practice as an antiepileptic drug; however, its mechanism of action remains unclear. In this study, we have characterized the action of α-asarone on the excitability of rat hippocampal neurons in culture and on the epileptic activity induced by pentylenetetrazole or kainate injection in vivo. Under cell-attached configuration, the firing rate of spontaneous spiking was inhibited by application of α-asarone, which was maintained in the Mg(2+)-free solution. Under whole-cell configuration, α-asarone induced inward currents in a concentration-dependent manner with an EC(50) of 248 ± 33 μM, which was inhibited by a GABA(A) receptor blocker picotoxin and a competitive GABA(A) receptor antagonist bicuculline but not a specific glycine receptor inhibitor strychnine. Measurement of tonic GABA currents and miniature spontaneous inhibitory postsynaptic currents indicated that α-asarone enhanced tonic GABAergic inhibition while left phasic GABAergic inhibition unaffected. In both pentylenetetrazole and kainate seizure models, α-asarone suppressed epileptic activity of mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure in vivo presumably dependent on the activation of GABA(A) receptors. In summary, our results suggest that α-asarone inhibits the activity of hippocampal neurons and produces antiepileptic effect in central nervous system through enhancing tonic GABAergic inhibition.

Topics: Acorus; Allylbenzene Derivatives; Animals; Anisoles; Anticonvulsants; Cells, Cultured; Epilepsy; HEK293 Cells; Hippocampus; Humans; Male; Mice; Mice, Inbred C57BL; Rats; Rats, Sprague-Dawley; Receptors, GABA-A

To study the effects of beta-asarone on expression of immediately early gene c-fos in kindling epilepsy rat brain.. The rats were randomly divided in to beta-asarone groups (200, 100, 50 mg x kg(-1) x d(-1)), difetoin control group (36 mg x kg(-1)) and model group. The remedy was administered orally. The effects were observed in kindling epilepsy model induced by penicillin, then the expression of c-fos were determined by western blot (hippocampus) and immunohistochemical techniques (cortex).. Beta-asarone could significantly increase the expression of c-fos in kindling epilepsy rat brain, and show its quantity-effect relation. The expression of c-fos in hippocampus was (1139.45 +/- 155.56), (1109.56 +/- 134.03), (1103.73 +/- 235.82) CNT x mm2 in beta-asarone groups, 920.54 +/- 203.20 in model control group, and 1106.26 +/- 186.24 in difetoin group, respectively. The number of c-fos positive cell was 87.1 +/- 2.2, 76.3 +/- 1.3 and 59.9 +/- 1.3 in beta-asarone groups, 39.3 +/- 2.6 in model control group, and 95.2 +/- 1.1 in difetoin group, respectively.. Beta-asarone can obviously increase the expression of c-fos in epilepsy rat brain. It is one of important response to epilepsy.

Topics: Allylbenzene Derivatives; Animals; Anisoles; Blotting, Western; Brain; Epilepsy; Female; Gene Expression; Immunohistochemistry; Male; Proto-Oncogene Proteins c-fos; Random Allocation; Rats; Rats, Sprague-Dawley

To study effects of beta-asarone on expression of FOS and GAD65 in cortex of epileptic rat induced by penicillin.. The epileptic animal models were induced by penicillin. The rats were randomly divided into beta-asarone of high (100 mg/kg), medium (50 mg/kg), low (25 mg/kg) dose group, positive control group (Phenytoin sodium), negative control group (matrix). The medicine was administered orally. The effects of beta-asarone on expression of FOS and GAD65 in cortex of epileptic rat were detected by immuohistochemistry method.. beta-asarone could raise expression of FOS and reduce expression of GAD65 obviously. There were significant differences between negative control group and beta-asarone group. And it showed significant dose-effect relationship.. Up-regulation of FOS may be a effective link of anti-epileptic effect of beta-asarone; reduced expression of GAD65 may be a follow-up impact of beta-asarone treatment.

Topics: Allylbenzene Derivatives; Animals; Anisoles; Anticonvulsants; Araceae; Cerebral Cortex; Drugs, Chinese Herbal; Epilepsy; Glutamate Decarboxylase; Immunohistochemistry; Male; Penicillins; Proto-Oncogene Proteins c-fos; Random Allocation; Rats; Rats, Sprague-Dawley

To study the effects of Annao tablet (main component is beta-asarone) on S100B and NPY of cortex in chronic epilepsy rats.. The remedy was administered orally. The effects were observed in convulsion model induced by PG, then S100B protein and NPY of cortex were determined.. Annao tablet could depress the epileptic degree, postpone spasm latent period and reduce the wet dog sample (WDS) times. The remedy could decline S100B and NPY of cortex in chronic epilepsy rats.. Annao tablet has obvious antiepileptic effects and can reduce the nerve cell damage induced by epilepsy.

Topics: Acorus; Allylbenzene Derivatives; Animals; Anisoles; Anticonvulsants; beta-Cyclodextrins; Cerebral Cortex; Drug Carriers; Epilepsy; Female; Male; Neuropeptide Y; Plants, Medicinal; Rats; Rats, Sprague-Dawley; S100 Proteins; Tablets