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Epimedium flavonoids protect neurons and synapses in the brain via activating NRG1/ErbB4 and BDNF/Fyn signaling pathways in a chronic cerebral hypoperfusion rat model.
Brain Res Bull. 2020 Sep; 162:132-140.BR

Abstract

Cerebral hypoperfusion is a common feature of cerebral small vascular disease (CSVD), which has been considered as one of the causes of cognitive decline in recent years. Epimedium flavonoids (EF) are the main ingredients extracted from Epimedium. The purpose of this study was to investigate the effects of EF on cognitive impairment, and the underlying mechanisms in rats with permanent occlusion of the bilateral common carotid artery (2VO). EF (50, 100, and 200 mg/kg) was intragastrically administered for 12 weeks starting 2 weeks after 2VO surgery. The results showed that EF treatment improved learning and memory impairment in 2VO rats evaluated by novel object recognition and Y-maze tests. NeuN immunohistochemical staining indicated that EF alleviated neuronal loss in the hippocampus and cerebral cortex of 2VO rats. MAP-2 immunofluorescence staining and western blotting showed that EF protected neuronal dendrites and increased the expression of cytoskeleton proteins MAP-2 and NF200 in the hippocampus of 2VO rats. Moreover, EF protected the synapse ultrastructure detected by transmission electron microscopy, and increased the expression of synaptic plasticity-related proteins, including synaptophysin, synaptotagmin-I, synapsin I, PSD-95, p-NMDA2B, and p-CaMKII-α in the hippocampus of 2VO rats. In addition, EF increased the expression of neuregulin-1 (NRG-1), p-ErbB4, brain-derived neurotrophic factor (BDNF), p-Fyn, PI3K, p-Akt, and p-CREB in the hippocampus of 2VO rats. These results suggest that EF may protect neurons and synapses by activating the NRG1/ErbB4, BDNF/Fyn, and P13 K/Akt/CREB pathways in the hippocampus and cerebral cortex, thus improving cognitive impairment induced by chronic cerebral hypoperfusion. EF may be a potential candidate drug for chronic cerebral hypoperfusion and CSVD therapy.

Authors+Show Affiliations

Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China.Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China. Electronic address: linlixw@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32592805

Citation

Niu, Hong-Mei, et al. "Epimedium Flavonoids Protect Neurons and Synapses in the Brain Via Activating NRG1/ErbB4 and BDNF/Fyn Signaling Pathways in a Chronic Cerebral Hypoperfusion Rat Model." Brain Research Bulletin, vol. 162, 2020, pp. 132-140.
Niu HM, Ma DL, Wang MY, et al. Epimedium flavonoids protect neurons and synapses in the brain via activating NRG1/ErbB4 and BDNF/Fyn signaling pathways in a chronic cerebral hypoperfusion rat model. Brain Res Bull. 2020;162:132-140.
Niu, H. M., Ma, D. L., Wang, M. Y., Chen, X. P., Zhang, L., Li, Y. L., Zhang, L., & Li, L. (2020). Epimedium flavonoids protect neurons and synapses in the brain via activating NRG1/ErbB4 and BDNF/Fyn signaling pathways in a chronic cerebral hypoperfusion rat model. Brain Research Bulletin, 162, 132-140. https://doi.org/10.1016/j.brainresbull.2020.06.012
Niu HM, et al. Epimedium Flavonoids Protect Neurons and Synapses in the Brain Via Activating NRG1/ErbB4 and BDNF/Fyn Signaling Pathways in a Chronic Cerebral Hypoperfusion Rat Model. Brain Res Bull. 2020;162:132-140. PubMed PMID: 32592805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epimedium flavonoids protect neurons and synapses in the brain via activating NRG1/ErbB4 and BDNF/Fyn signaling pathways in a chronic cerebral hypoperfusion rat model. AU - Niu,Hong-Mei, AU - Ma,Deng-Lei, AU - Wang,Ming-Yang, AU - Chen,Xiao-Ping, AU - Zhang,Li, AU - Li,Ya-Li, AU - Zhang,Lan, AU - Li,Lin, Y1 - 2020/06/24/ PY - 2020/03/30/received PY - 2020/06/02/revised PY - 2020/06/19/accepted PY - 2020/6/28/pubmed PY - 2020/6/28/medline PY - 2020/6/28/entrez KW - BDNF KW - Cerebral small vascular disease KW - Cognitive impairment KW - Epimedium flavonoids KW - Fyn KW - P13K/Akt/CREB KW - RG1/ErbB4 KW - Synapse SP - 132 EP - 140 JF - Brain research bulletin JO - Brain Res. Bull. VL - 162 N2 - Cerebral hypoperfusion is a common feature of cerebral small vascular disease (CSVD), which has been considered as one of the causes of cognitive decline in recent years. Epimedium flavonoids (EF) are the main ingredients extracted from Epimedium. The purpose of this study was to investigate the effects of EF on cognitive impairment, and the underlying mechanisms in rats with permanent occlusion of the bilateral common carotid artery (2VO). EF (50, 100, and 200 mg/kg) was intragastrically administered for 12 weeks starting 2 weeks after 2VO surgery. The results showed that EF treatment improved learning and memory impairment in 2VO rats evaluated by novel object recognition and Y-maze tests. NeuN immunohistochemical staining indicated that EF alleviated neuronal loss in the hippocampus and cerebral cortex of 2VO rats. MAP-2 immunofluorescence staining and western blotting showed that EF protected neuronal dendrites and increased the expression of cytoskeleton proteins MAP-2 and NF200 in the hippocampus of 2VO rats. Moreover, EF protected the synapse ultrastructure detected by transmission electron microscopy, and increased the expression of synaptic plasticity-related proteins, including synaptophysin, synaptotagmin-I, synapsin I, PSD-95, p-NMDA2B, and p-CaMKII-α in the hippocampus of 2VO rats. In addition, EF increased the expression of neuregulin-1 (NRG-1), p-ErbB4, brain-derived neurotrophic factor (BDNF), p-Fyn, PI3K, p-Akt, and p-CREB in the hippocampus of 2VO rats. These results suggest that EF may protect neurons and synapses by activating the NRG1/ErbB4, BDNF/Fyn, and P13 K/Akt/CREB pathways in the hippocampus and cerebral cortex, thus improving cognitive impairment induced by chronic cerebral hypoperfusion. EF may be a potential candidate drug for chronic cerebral hypoperfusion and CSVD therapy. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/32592805/Epimedium_flavonoids_protect_neurons_and_synapses_in_the_brain_via_activating_NRG1/ErbB4_and_BDNF/Fyn_signaling_pathways_in_a_chronic_cerebral_hypoperfusion_rat_model L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(20)30537-2 DB - PRIME DP - Unbound Medicine ER -
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