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.

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.