cinidon-ethyl and Cognition-Disorders

This study mainly investigated the ameliorative effect of lotus seedpod proanthocyanidins (LSPC) and the mechanism underlying such effect on cognitive impairment and brain aging induced by d-galactose. Aging mice induced by d-galactose (150 mg/kg, sc injection daily for 6 weeks) were chosen for the experiment. LSPCs (30, 60, and 90 mg/kg, ig) were provided after d-galactose injection. Learning and memory functions were detected by Y-maze and step-down avoidance tests. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature and P53 protein expression in the hippocampus were observed. Results showed that the three different doses of LSPC could significantly ameliorate the learning and memory abilities impaired by d-galactose. LSPC significantly reduced the levels of malondialdehyde and nitric oxide (i.e. 90 mg/kg LSPC group vs. model group, P=0.008), reduced the content of β-amyloid peptide 1-42 (i.e. 90 mg/kg LSPC group vs. model group, P=0.009), decreased the activities of acetylcholinesterase, monoamine oxidase B, total nitric oxide synthase (i.e. 90 mg/kg LSPC group vs. model group, P=0.006), and neuronal nitric oxide synthase and synchronously increased the activities of superoxide dismutase and glutathione peroxidase in the brain. Furthermore, LSPC could prevent neuron damage and could lessen the expression of P53 protein in the hippocampus. These findings demonstrated that LSPC effectively attenuated cognitive damage and improved parameters related to brain aging in senescent mice induced by d-galactose, and may be used to treat Alzheimer's disease.

Topics: Age Factors; Aging; Animals; Avoidance Learning; Behavior, Animal; Biomarkers; Cognition; Cognition Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Galactose; Hippocampus; Lotus; Male; Maze Learning; Memory; Mice; Neurons; Neuroprotective Agents; Phytotherapy; Plant Extracts; Plants, Medicinal; Proanthocyanidins; Seeds; Time Factors

Lotus seedpod procyanidins (LSPCs) could effectively prevent learning and memory damage and oxidative damage caused by extremely low frequency electromagnetic field (ELF-EMF) exposure. However, LSPCs protect neurons from ELF-EMF-induced damage by mechanisms currently not clear. An excessive release of glutamate is considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. In this study we determined whether the ELF-EMF (50 Hz, 8 mT, 28 days) exposure induced alterations of glutamate release in mice hippocampus and explored the possible mechanism, and if LSPC treatment normalized its alterations. The results showed that ELF-EMF exposure induced the increased contents of glutamate, GABA, excessively activated NMDA receptors, increasing the number of NMDA receptor 2B (NR2B) and intracellular Ca(2+) concentration [Ca(2+)]i in hippocampus. In addition, ELF-EMF exposure decreased the ERK1/2 and CREB phosphorylation, which suggested that the Ca(2+) influx induced by the ELF-EMF exposure stimulated activity of the ERK, in turn, influences the expression of downstream proteins in this signaling pathway. Besides, ELF-EMF exposure also increased JNK1/2 phosphorylation through the activated ASK1, which plays a pivotal role in hippocampal neuronal cell death. However, oral administration of LSPCs (especially 60 and 90 mg kg(-1)) markedly improved expressions of p-CREB, p-ERK1/2 and p-JNK1/2, accompanied by decreased levels of glutamate, GABA, [Ca(2+)]i and NR2B. Thus, the results from the present study suggest that p-ERK1/2, p-JNK1/2, [Ca(2+)]i and p-CREB expression normalized, possibly via a NMDA receptor-channel through the changes of GABA, glutamate and NR2B, which might be responsible for the neuroprotective or memory enhancing effects of LSPCs.

Topics: Animals; Biflavonoids; Catechin; Cognition Disorders; CREB-Binding Protein; Glutamic Acid; Hippocampus; Humans; Lotus; Male; MAP Kinase Signaling System; Mice; Mice, Inbred ICR; Phosphorylation; Plant Extracts; Proanthocyanidins

The present study investigated the effects of lotus seedpod procyanidins (LSPCs) administered by oral gavage on the cognitive deficits and oxidative damage of mice at extremely low frequency electromagnetic field (ELF-EMF) exposure (50 Hz, 8 mT, 28 days). The results showed that 90 mg kg⁻¹ LSPCs treatment significantly increased body weight compared with the ELF-EMF group at ELF-EMF exposure and effectively maintained liver index, thymus index, kidney index and spleen index close to normal. A water maze test indicated that learning and memory abilities of the ELF-EMF group deteriorated significantly with ELF-EMF exposure when compared with the control group, but the ELF-EMF + LSPCs90 group had remarkably improved learning and memory abilities compared with the ELF-EMF group. Malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO) and nitric oxide synthase (NOS) mostly exhibited significant increases, while the activities of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) decreased significantly under ELF-EMF exposure in the ELF-EMF group. LSPCs (especially 60, 90 mg kg⁻¹) administration decreased MDA, ROS, NO content and lowered NOS activity in LSPCs treatment groups. Furthermore, LSPCs (60, 90 mg kg⁻¹) treatment significantly augmented GPx, CAT, SOD activity in the hippocampus and serum. Pathological observation showed that number of pyramidal cells of the CA1 and CA3 regions of the hippocampus of the LSPCs treatment groups was significantly greater than the ELF-EMF group. All the data suggested that the LSPCs can effectively prevent learning and memory damage and oxidative damage caused by the ELF-EMF, most likely through the ability of LSPCs to scavenge oxygen free radicals and to stimulate antioxidant enzyme activity.

Topics: Animals; Antioxidants; Cognition Disorders; Electromagnetic Fields; Glutathione Peroxidase; Hippocampus; Humans; Learning; Lipid Peroxidation; Lotus; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Oxidative Stress; Plant Extracts; Proanthocyanidins; Seeds; Superoxide Dismutase

The major purpose of this study was to determine the effects of procyanidins extracted from the lotus seedpod on cAMP-response element-binding protein phosphorylation in hippocampus and cerebral cortex in cognitively impaired aged rats. Based on Morris water maze, aged unimpaired and aged impaired rats were chosen from aged rats. Comparing with young and aged unimpaired animals, aged impaired rats exhibited significant reduction in hippocampal but not cortical cAMP-response element-binding phosphorylation states as well as brain-derived neurotrophic factor messenger RNA and protein expressions, which were accompanied by decreased phosphorylation states of hippocampal extracellular signal-related kinase (42/44) and calcium calmodulin kinase IV. Lotus seedpod supplementation (50 and 100 mg/kg body weight intragastric administration) for 7 weeks significantly reversed all these declines happened in hippocampus except calcium calmodulin kinase IV phosphorylation levels. These results suggested that lotus seedpod might enhance cAMP-response element-binding-dependent transcription through the activation of extracellular signal-related kinase signalling pathway, which might contribute to its ameliorative effects on cognitive deficits in aged impaired animals.

Topics: Aging; Animals; Brain-Derived Neurotrophic Factor; Calcium-Calmodulin-Dependent Protein Kinase Type 4; Cerebral Cortex; Cognition Disorders; CREB-Binding Protein; Extracellular Signal-Regulated MAP Kinases; Female; Hippocampus; Lotus; Maze Learning; Memory Disorders; Phosphorylation; Plant Extracts; Proanthocyanidins; Protein Kinase C-alpha; Rats; Rats, Sprague-Dawley; RNA, Messenger

The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments in cognitively impaired aged rats. Based on Morris water maze performance compared with young female rats, aged unimpaired (AU) and aged impaired (AI) rats were chosen from aged female rats. LSPC supplementation (50, 100 mg/kg BW, p.o.) for 7 weeks significantly improved learning and memory impairments in AI animals in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. Aged rats had significantly declined antioxidant defense capacities and significantly increased lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex than young rats. Further, AI group had higher protein oxidation level compared with AU group. LSPC (50, 100 mg/kg BW, p.o.) significantly reversed the decline of antioxidant defense capacities and significantly reduced lipid peroxidation and protein oxidation levels in hippocampus and cerebral cortex of AI rats. In addition, LSPC significantly restored acetylcholine (ACh) contents and acetylcholinesterase (AChE) activities in hippocampus and cerebral cortex of AI animals. The results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by Alzheimer's disease and aging.

Topics: Acetylcholine; Acetylcholinesterase; Age Factors; Animals; Antioxidants; Cognition Disorders; Dose-Response Relationship, Drug; Female; Glutathione; Glutathione Peroxidase; Lotus; Maze Learning; Memory Disorders; Phytotherapy; Plant Extracts; Proanthocyanidins; Protein Carbonylation; Rats; Rats, Sprague-Dawley; Rejuvenation; Seeds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances