alpha-asarone and Infarction--Middle-Cerebral-Artery

BACKGROUND This study assessed the effects and underlying molecular mechanisms of ß-asarone on ischemic stroke model rats. MATERIAL AND METHODS Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) in rats. Before and after modeling, cognitive function was evaluated via fear conditioning test and neurological deficit was determined via Longa and Bederson scores. Following treatment with ß-asarone or nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor for 20 consecutive days, the cerebral infarction was detected via TTC staining and Cresyl Violet staining in brain tissues. TUNEL staining and western blot analysis for apoptosis-related proteins were performed to assess the apoptosis of neurons. Nrf2-antioxidant response elements (ARE) pathway-related proteins were examined by RT-qPCR or western blot. RESULTS The cognitive and neurological function was defective in MCAO rats. The infarction volumes and the apoptosis of cortical neurons were significantly increased in brain tissues of model rats, which were ameliorated after treatment with ß-asarone. Meanwhile, the increase in pro-apoptotic proteins and decrease in anti-apoptotic proteins were found in brain tissues of model rats, which were markedly ameliorated by ß-asarone treatment. However, Nrf2 inhibitor worsened the cerebral infarction and the apoptosis of neurons. Western blot results showed that ß-asarone treatment activated the Nrf2-ARE pathway-related proteins in model rats, which was inhibited by Nrf2 inhibitor. CONCLUSIONS Our findings suggest that ß-asarone treatment ameliorated the cerebral infarction in MCAO rats, which could be related to activation of the Nrf2-ARE pathway.

Topics: Allylbenzene Derivatives; Animals; Anisoles; Antioxidant Response Elements; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Asarum; Behavior, Animal; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Ischemic Stroke; Neurons; Neuroprotective Agents; NF-E2-Related Factor 2; Rats; Signal Transduction

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.

Topics: Allylbenzene Derivatives; Animals; Anisoles; Apoptosis; Autophagy; Brain Ischemia; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Rats; Reperfusion; Reperfusion Injury; Stroke

Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. β-Asarone, which has significant pharmacological effects on the central nervous system (CNS), was used in the prevention of cerebral ischemia in this paper.. The right middle cerebral artery occlusion model was used in the study. The effects of β-Asarone on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na⁺-K⁺-ATPase activity and glutathione S transferase activity in a rat model were studied respectively.. β-Asarone significantly improved the neurological outcome after cerebral ischemia and reperfusion in terms of neurobehavioral function in rats. Meanwhile, supplementation of β-Asarone significantly boosted the defense mechanism against cerebral ischemia via increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may help the brain recover from ischemic injury.. These experimental results suggest that complement β-Asarone is protective against cerebral ischemia in specific way. The administration of β-Asarone could reduce focal cerebral ischemic/reperfusion injury. The Mechanism of β-Asarone in protection of cerebral ischemia was via increasing antioxidants activity related to lesion pathogenesis.

Topics: Acorus; Allylbenzene Derivatives; Analysis of Variance; Animals; Anisoles; Behavior, Animal; Hand Strength; Infarction, Middle Cerebral Artery; Male; Oxidative Stress; Plant Extracts; Protective Agents; Rats; Rats, Wistar

Beta-asarone has significant pharmacological effects on the central nervous system. It can attenuate neuronal apoptosis, but its effects on the brain ischemia-reperfusion-induced autophagy have not been reported yet. Our study was a two-stage procedure: evaluation of β-asarone effects on the autophagy at first, and then analysis of the possible mechanism. The middle cerebral artery occlusion (MCAO) model was adopted to make the brain injure and Beclin 1 was used to evaluate the autophagy. We hypothesized that the mechanism might be related to c-Jun N-terminal kinases (JNK), phospho-JNK (p-JNK), Bcl-2 and Beclin 1. To test this hypothesis, we evaluated JNK, p-JNK, Bcl-2 and Beclin 1 levels with flow cytometry. Additionally, we divided the brain into three regions: ischemic region, ischemic penumbra, and normal region, and analyzed them respectively. We found, compared to both groups II (model control) and III (low dose), Beclin 1 levels in groups IV (medium dose) and V (high dose) were significantly decreased. Beclin 1, JNK and p-JNK levels in groups VII (β-asarone) and VIII (JNK inhibitor) were significantly decreased, but Bcl-2 levels were significantly increased. Additionally, Beclin 1, JNK, p-JNK and Bcl-2 levels among the three regions had no significant differences. We conclude that β-asarone can attenuate the autophagy in a dose-dependent manner. The mechanism is likely that β-asarone can decrease JNK and p-JNK levels at first, and then increase Bcl-2 level, finally interfere with the functions of Beclin 1 during the execution of autophagy. Additionally, β-asarone can attenuate autophagy in a widespread manner.

Topics: Allylbenzene Derivatives; Animals; Anisoles; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Brain; Brain Ischemia; Infarction, Middle Cerebral Artery; JNK Mitogen-Activated Protein Kinases; Middle Cerebral Artery; Phosphopyruvate Hydratase; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Reperfusion Injury