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.

Neuroprotective effect of Chunghyuldan (Qing Xue Dan) on hypoxia-reoxygenation induced damage of neuroblastoma 2a cell lines / 中国结合医学杂志

<p><b>OBJECTIVES</b>Chunghyuldan (CHD), a combinatorial drug that has anti-hyperlipidemic and antiinflammatory activities, has been shown to reduce infarct volume in a focal ischemia-reperfusion rat model. To explore the molecular basis of CHD's neuroprotective effect, we examined whether CHD shows a cell-protective activity and has a regulatory effect on Bax and/or B-cell leukemia/lymphoma 2 (Bcl-2) expression in mouse neuroblastoma 2a (N2a) cells subjected to hypoxia-reoxygenation (H/R).</p><p><b>METHODS</b>In order to evaluate the effects of CHD on the cytotoxicity induced from hypoxia or H/R condition, lactate dehydrogenase (LDH) assay was performed. To explore whether the suppression of neural damage when pre-treated with CHD is associated with its anti-apoptotic effect, the CHD effect on the expression of Bcl-2 and Bax was analyzed by Western blotting analysis.</p><p><b>RESULTS</b>Cytotoxicity of N2a cell line was slightly increased in 42 h hypoxia condition and dramatically increased under the H/R condition. CHD treatment markedly decreased the cytotoxicity in both conditions (P<0.01, P<0.05). H/R markedly increased the expression of the pro-apoptotic protein, Bax, but slightly increased the expression of the anti-apoptotic protein, Bcl-2, compared with the normoxia or hypoxia group. CHD significantly decreased Bax expression (P<0.01) and slightly decreased Bcl-2 expression (P>0.05), resulted in a reduction of Bax/Bcl-2 ratio in N2a cells subjected to H/R.</p><p><b>CONCLUSION</b>CHD has neuroprotective effect in N2a cells subjected to H/R, which might be derived at least in part from its ability to decrease the expression of the pro-apoptotic protein, Bax.</p>