alpha-asarone and Cognition-Disorders

The aim of this study investigates whether β-asarone can improve cognition deficits in dizocilpine (MK-801) treated mice. Six-week-old male C57BL/6 mice were divided into four groups: control group (CON), MK-801-treated group (MK-801), MK-801 plus β-asarone group (MK-801+β-asa) and β-asarone group (β-asa). Behavioral tests, including sociability test, open field test (OPT) and Morris water-maze (MWM), were performed. Extracellular field excitatory postsynaptic potentials were recorded in the hippocampal dentate gyrus (DG) region. Western blot was employed to measure the expression of cognitive function-associated proteins and pro-inflammatory cytokines in the hippocampus. Immunofluorescence was performed to assess the microglial activation in the hippocampus DG region. The data show that social interactions and spatial learning and memory were impaired by MK-801. However, β-asarone significantly mitigated the impairments. Furthermore, it was found that MK-801 aggravated the hyperactivity and anxiety-like behavior, but β-asarone alleviated them. Moreover, β-asarone alleviated the impairments of hippocampal synaptic plasticity and enhanced the expression of hippocampal synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) in MK-801-treated mice. In addition, it suppressed the expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), inducible nitric oxide synthase (i-Nos) and cyclo-oxygenase-2 (COX-2) expression in MK-801-treated mice. The results suggest that β-asarone improved the impairment of cognition and synaptic plasticity possibly through modulating the excess release of pro-inflammatory cytokines and microglia activation in MK-801-treated mice.

Topics: Allylbenzene Derivatives; Animals; Anisoles; Anti-Inflammatory Agents; Brain; Cognition; Cognition Disorders; Disks Large Homolog 4 Protein; Dizocilpine Maleate; Hippocampus; Interpersonal Relations; Male; Memory; Mice; Mice, Inbred C57BL; Microglia; Neuronal Plasticity; Neuroprotective Agents; Nitric Oxide Synthase Type II; Social Behavior; Synaptophysin

β-Asarone is an active component of the Acori graminei rhizome that is a traditional Chinese medicine clinically used in treating dementia in China. However, the cognitive effect of β-asarone and its mechanism has remained elusive. Here, we used asenescence-accelerated prone 8 (SAMP8) mice, which mimic many of the salient features of Alzheimer׳s disease (AD), to further investigate whether modulation of the ROCK signaling pathway and/or autophagy, synaptic loss is involved in the effects of β-asarone on learning and memory. SAMP8 mice at the age of 6 months were intragastrically administered by β-asarone or a vehicle daily for 2 months. Senescence-accelerated-resistant (SAMR1) mice were used as the control. Our results demonstrate that autophagy and ROCK expression were increased significantly in 8 months SAMP8 mice, which were concomitant with that SAMP8 mice at the same age displayed a significant synaptic loss and cognitive deficits. The up-regulation of ROCK expression and autophage in the hippocampus of SAMP8 were significantly reduced by β-asarone, and prevents synaptic loss and improved cognitive function of the SAMP8 mice. β-asarone decreased neuronophagia and lipofuscin in the hippocampus of SAMP8 mice, but did not reduce Aβ42 levels and malondialdehyde levels and superoxide dismutase activities. Moreover, suppression of ROCK2 by siRNA significantly reduced the effects of β-asarone on the autophage and synaptic proteins expression in PC12 cells damage induced by Aβ1-40. Taken together, β-asarone prevents autophagy and synaptic loss by reducing ROCK expression in SAMP8 mice.

Topics: Aging, Premature; Allylbenzene Derivatives; Amyloid beta-Peptides; Animals; Anisoles; Autophagy; CA3 Region, Hippocampal; Cognition Disorders; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Enzyme Induction; Lipofuscin; Long-Term Potentiation; Malondialdehyde; Maze Learning; Mice; Microtubule-Associated Proteins; Nerve Tissue Proteins; Neuroprotective Agents; Oxidative Stress; PC12 Cells; Peptide Fragments; Rats; rho-Associated Kinases; RNA Interference; RNA, Small Interfering; Superoxide Dismutase; Synapses; Up-Regulation

Elevated levels of beta-amyloid (Abeta) in the brains being a hallmark of Alzheimer's disease (AD) have been believed to play a critical role in the cognitive dysfunction that occurs in AD. Recent evidence suggests that Abeta induces neuronal apoptosis in the brain and in primary neuronal cultures. In this study, we investigated the effects of beta-asarone, the major ingredient of Acorus Tatarinowii Schott, on cognitive function and neuronal apoptosis in Abeta hippocampus injection rats and its mechanism of action. The results show that the Abeta (1-42) injection caused impairments in spatial reference memory in a Morris water maze task and apoptosis in hippocampus. Oral administration of beta-asarone with three different dose (12.5, 25, or 50 mg/kg) for 28 d ameliorated Abeta (1-42)-induced cognitive impairment and reversed the increase of apoptosis in the hippocampus. Abeta-induced c-Jun N-terminal kinase (JNK) results in phosphorylation, subsequent down-regulation of Bcl-2 and Bcl-w expression, and caspase-3 activation. Beta-asarone attenuate Abeta (1-42)-induced neuronal apoptosis in hippocampus by reversal down-regulation of Bcl-2, Bcl-w, caspase-3 activation, and JNK phosphorylation. These results suggest that beta-asarone may be a potential candidate for development as a therapeutic agent to manage cognitive impairment associated with conditions such as Alzheimer's disease.

Topics: Acorus; Allylbenzene Derivatives; Amyloid beta-Peptides; Animals; Anisoles; Apoptosis; Caspase 3; Cognition; Cognition Disorders; Down-Regulation; Hippocampus; JNK Mitogen-Activated Protein Kinases; Male; Maze Learning; Neurons; Phosphorylation; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; RNA, Messenger