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Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits by Inhibiting Oxidative Stress and Preserving AKT and ERK Activities.
Curr Med Sci. 2020 Jun; 40(3):434-443.CM

Abstract

Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer's disease (AD). Currently, there is no effective drug available for the treatment of AD. Previous studies have demonstrated that the cognitive impairment of AD is associated with oxidative stress and the inhibition of AKT and ERK phosphorylation. Grape seed proanthocyanidin extract (GSPE) has been shown to have strong antioxidant effect and can protect the nervous system from oxidative stress damage. This study aimed to investigate the protective effect of GSPE on the cognitive and synaptic impairments of AD using a sporadic AD rat model induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) (ICV-STZ). Rats were treated with GSPE (50, 100, or 200 mg/kg every day) by intragastrical (ig.) administration for continuous 7 weeks, and ICV-STZ (3 mg/kg) was performed on the first day and third day of week 5. Learning and memory abilities were assessed by the Morris water maze (MWM) test at week 8. After behavioral test, hippocampal long-term potentiation (LTP) was recorded, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), glutathione (GSH) and the protein expression of AKT and ERK were measured in the hippocampus and cerebral cortex of rats. Our study revealed that ICV-STZ significantly impaired the working learning ability and hippocampal LTP of rats, significantly increased the levels of MDA, and decreased the activity of SOD and GSH in the hippocampus and cerebral cortex. In contrast, GSPE treatment prevented the impairment of cognitive function and hippocampal LTP induced by ICV-STZ, decreased the level of MDA, and increased the level of SOD and GSH. Furthermore, Western blot results showed that GSPE treatment could prevent the loss of AKT and ERK activities in the hippocampus and cerebral cortex induced by ICV-STZ. Our findings demonstrate that GSPE treatment could ameliorate the impairment of cognitive ability and hippocampal synaptic plasticity in a rat model of sporadic AD by inhibiting oxidative stress and preserving AKT and ERK activities. Therefore, GSPE may be an effective agent for the treatment of cognitive deficits associated with sporadic AD.

Authors+Show Affiliations

School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, China. Hubei Key Laboratory of Cardiovascular Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, China. Department of Pharmacy, Huangshi Central Hospital, Afiliated Hospial of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, 435000, China.School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, China.School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, China.School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, China.School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, China.School of Pharmacy, Hubei University of Science and Technology, Xianning, 437100, China. yxyliyk@163.com. Hubei Key Laboratory of Cardiovascular Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, China. yxyliyk@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32681248

Citation

Gao, Wei-Li, et al. "Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits By Inhibiting Oxidative Stress and Preserving AKT and ERK Activities." Current Medical Science, vol. 40, no. 3, 2020, pp. 434-443.
Gao WL, Li XH, Dun XP, et al. Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits by Inhibiting Oxidative Stress and Preserving AKT and ERK Activities. Curr Med Sci. 2020;40(3):434-443.
Gao, W. L., Li, X. H., Dun, X. P., Jing, X. K., Yang, K., & Li, Y. K. (2020). Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits by Inhibiting Oxidative Stress and Preserving AKT and ERK Activities. Current Medical Science, 40(3), 434-443. https://doi.org/10.1007/s11596-020-2197-x
Gao WL, et al. Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits By Inhibiting Oxidative Stress and Preserving AKT and ERK Activities. Curr Med Sci. 2020;40(3):434-443. PubMed PMID: 32681248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits by Inhibiting Oxidative Stress and Preserving AKT and ERK Activities. AU - Gao,Wei-Li, AU - Li,Xiang-Hua, AU - Dun,Xin-Peng, AU - Jing,Xiao-Kuan, AU - Yang,Ke, AU - Li,Yan-Kun, Y1 - 2020/07/17/ PY - 2020/05/20/received PY - 2020/06/25/revised PY - 2020/7/19/entrez PY - 2020/7/19/pubmed PY - 2021/5/19/medline KW - AKT/ERK signaling KW - Alzheimer’s disease KW - cognitive ability KW - grape seed proanthocyanidin extract KW - oxidative stress KW - synaptic plasticity SP - 434 EP - 443 JF - Current medical science JO - Curr Med Sci VL - 40 IS - 3 N2 - Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer's disease (AD). Currently, there is no effective drug available for the treatment of AD. Previous studies have demonstrated that the cognitive impairment of AD is associated with oxidative stress and the inhibition of AKT and ERK phosphorylation. Grape seed proanthocyanidin extract (GSPE) has been shown to have strong antioxidant effect and can protect the nervous system from oxidative stress damage. This study aimed to investigate the protective effect of GSPE on the cognitive and synaptic impairments of AD using a sporadic AD rat model induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) (ICV-STZ). Rats were treated with GSPE (50, 100, or 200 mg/kg every day) by intragastrical (ig.) administration for continuous 7 weeks, and ICV-STZ (3 mg/kg) was performed on the first day and third day of week 5. Learning and memory abilities were assessed by the Morris water maze (MWM) test at week 8. After behavioral test, hippocampal long-term potentiation (LTP) was recorded, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), glutathione (GSH) and the protein expression of AKT and ERK were measured in the hippocampus and cerebral cortex of rats. Our study revealed that ICV-STZ significantly impaired the working learning ability and hippocampal LTP of rats, significantly increased the levels of MDA, and decreased the activity of SOD and GSH in the hippocampus and cerebral cortex. In contrast, GSPE treatment prevented the impairment of cognitive function and hippocampal LTP induced by ICV-STZ, decreased the level of MDA, and increased the level of SOD and GSH. Furthermore, Western blot results showed that GSPE treatment could prevent the loss of AKT and ERK activities in the hippocampus and cerebral cortex induced by ICV-STZ. Our findings demonstrate that GSPE treatment could ameliorate the impairment of cognitive ability and hippocampal synaptic plasticity in a rat model of sporadic AD by inhibiting oxidative stress and preserving AKT and ERK activities. Therefore, GSPE may be an effective agent for the treatment of cognitive deficits associated with sporadic AD. SN - 2523-899X UR - https://www.unboundmedicine.com/medline/citation/32681248/Grape_Seed_Proanthocyanidin_Extract_Ameliorates_Streptozotocin_induced_Cognitive_and_Synaptic_Plasticity_Deficits_by_Inhibiting_Oxidative_Stress_and_Preserving_AKT_and_ERK_Activities_ L2 - https://doi.org/10.1007/s11596-020-2197-x DB - PRIME DP - Unbound Medicine ER -