hyperoside and Memory-Disorders

Alzheimer's disease (AD) is the most common degenerative disease and is indicative of dementia. The cerebral accumulation of amyloid β (Aβ), a crucial factor in AD, initiates synaptic and cognitive dysfunction. Therefore, the elevation of synaptic and cognitive functions may help manage dementia in AD. In this study, we suggest hyperoside as a synaptic function- and memory-enhancing agent. Hyperoside enhanced learning and memory in passive avoidance and object recognition tasks. Hyperoside facilitated synaptic long-term potentiation (LTP) in acute hippocampal slices. IEM-1460, a calcium-permeable amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) antagonist, blocked the facilitation effect of hyperoside. Hyperoside also induced N-methyl-d-aspartate receptor (NMDAR)-independent LTP, which was blocked by IEM-1460, suggesting the involvement of CP-AMPARs in the synaptic effects of hyperoside-mediated LTP. PKI (a PKA inhibitor) or SQ22536 (adenylyl cyclase, an AC inhibitor) blocked hyperoside-facilitated LTP and hyperoside-induced NMDAR-independent LTP. Hyperoside-enhanced learning and memory were blocked by IEM-1460, suggesting the involvement of CP-AMPARs in the effect of hyperoside on learning and memory. Finally, hyperoside ameliorated Aβ-induced memory impairments in an AD mouse model. These results suggest that hyperoside enhances learning and memory, and this may be due to the effect of CP-AMPARs.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Calcium; Hippocampus; Long-Term Potentiation; Memory Disorders; Mice; Quercetin; Receptors, AMPA; Synapses

Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid mainly found in fruits, fruit juices (most notably flavanols, flavanones, and anthocyanins) and Chinese traditional medicines. It has been applied to relieve pain and improve cardiovascular functions in clinic. However, the effects of hyperoside on cognitive impairment induced by chronic stress and the underlying molecular mechanisms remain unclear. In the current study, we used chronic mild stress (CMS) rats to investigate the effects of hyperoside on learning and memory and further explore the possible mechanisms. Our results demonstrated that hyperoside reduced the escape latency and the swimming distance of CMS rats in Morris water maze test and reversed depressive symptoms in forced swim test (FST) and sucrose preference test. In addition, hyperoside increased the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a, an inhibitor of the BDNF receptor TrkB, prevented the protective effects of hyperoside on learning and memory in CMS rats. Taken together, these results indicate that hyperoside reverses the cognitive impairment induced by CMS, which is associated with the regulation of BDNF signaling pathway.

Topics: Animals; Brain-Derived Neurotrophic Factor; Carbazoles; Chronic Disease; Cognition; Corticosterone; Depression; Hippocampus; Indole Alkaloids; Learning; Male; Maze Learning; Memory Disorders; Neuroprotective Agents; Quercetin; Rats, Sprague-Dawley; Receptor, trkB; Stress, Psychological

To investigate the effects of active constituents extracted from Cortex Acanthopanacis Radicison improving the impaired memory in mice models.. The mice models of memory impairment were established using scopolamine. Ameliorating effects of the fractions and constituents on scopolamine-induced memory impairment in vivo were investigated using passive avoidance and Morris water-maze task tests, and their anti-acetylcholinesterase (AChE) and antioxidant activities in vitro examined. The isolation of constituents was performed by chromatographic methods and their structures were identified on the basis of instrumental analysis.. Among the fractions tested, ethylacetate fraction exhibited the anti-AChE activity (25.83% +/- 0.23%) properly and excellent 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical and superoxide anion scavenging capacity (87.50% +/- 0.83% and 60.22% +/- 0.43%, respectively). However, the methylene chloride fraction was much more active than the ethyl-acetate fraction in the passive avoidance task test (167.5% increase of step-through latency time) and Morris water-maze task 33.2% decrease of escape latency time). Four constituents, beta-sitosterol, stigmasterol, sesamin, and hyperin were isolated from the methylene chloride fraction, among them, hyperin showed anti-acetylcholinesterase and anti-oxidant activities remarkably. Moreover, hyperin exerted a potent effect (146 +/- 38) s on memory improvement in terms of passive avoidance task test compared with the reference compound tacrine (162 +/- 43) s at a dose of 2.5 mg/kg.. Hyperin, a flavonoid glucoside isolated from Cortex Acanthopanacis Radicis, inhibited AChE activity and potently ameliorated scopolamine-induced memory impairment, and its action may be partially mediated by the acetylcholine-enhancing cholinergic nervous system.

Topics: Acetylcholinesterase; Animals; Cholinesterase Inhibitors; Drugs, Chinese Herbal; Eleutherococcus; Humans; Male; Memory Disorders; Mice; Mice, Inbred ICR; Quercetin; Scopolamine