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Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice.
CNS Neurosci Ther 2016; 22(1):63-73CN

Abstract

AIMS

This study investigated the neuroprotective properties of icariin (an effective component of traditional Chinese herbal medicine Epimedium) on neuronal function and brain energy metabolism maintenance in a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD).

METHODS

3 × Tg-AD mice as well as primary neurons were subjected to icariin treatment. Morris water maze assay, magnetic resonance spectroscopy (MRS), Western blotting, ELISA, and immunohistochemistry analysis were used to evaluate the effects of icariin administration.

RESULTS

Icariin significantly improved spatial learning and memory retention in 3 × Tg-AD mice, promoted neuronal cell activity as identified by the enhancement of brain metabolite N-acetylaspartate level and ATP production in AD mice, preserved the expressions of mitochondrial key enzymes COX IV, PDHE1α, and synaptic protein PSD95, reduced Aβ plaque deposition in the cortex and hippocampus of AD mice, and inhibited β-site APP cleavage enzyme 1 (BACE1) expression. Icariin treatment also decreased the levels of extracellular and intracellular Aβ1-42 in 3 × Tg-AD primary neurons, modulated the distribution of Aβ along the neurites, and protected against mitochondrial fragmentation in 3 × Tg-AD neurons.

CONCLUSIONS

Icariin shows neuroprotective effects in 3 × Tg-AD mice and may be a promising multitarget drug in the prevention/protection against AD.

Links

Publisher Full Text

ncbi.nlm.nih.gov

Aggregator Full Text

Authors+Show Affiliations

College of Life Science, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China.

College of Life Science, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China.

College of Life Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, China.

College of Life Science, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China.

College of Life Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, China.

College of Life Science, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China.

College of Life Science, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China.

MeSH

Alzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsBrainCells, CulturedCognitionDisease Models, AnimalDrug Evaluation, PreclinicalFemaleFlavonoidsHumansMaze LearningMice, TransgenicMitochondriaNeuronsNeuroprotective AgentsPresenilin-1Spatial Memorytau Proteins

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26584824

Citation

Chen, Yi-Jing, et al. "Neuroprotective Effects of Icariin On Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice." CNS Neuroscience & Therapeutics, vol. 22, no. 1, 2016, pp. 63-73.

Chen YJ, Zheng HY, Huang XX, et al. Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice. CNS Neurosci Ther. 2016;22(1):63-73.

Chen, Y. J., Zheng, H. Y., Huang, X. X., Han, S. X., Zhang, D. S., Ni, J. Z., & He, X. Y. (2016). Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice. CNS Neuroscience & Therapeutics, 22(1), pp. 63-73. doi:10.1111/cns.12473.

Chen YJ, et al. Neuroprotective Effects of Icariin On Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice. CNS Neurosci Ther. 2016;22(1):63-73. PubMed PMID: 26584824.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice. AU - Chen,Yi-Jing, AU - Zheng,Hai-Yang, AU - Huang,Xiu-Xian, AU - Han,Shuang-Xue, AU - Zhang,Dong-Sheng, AU - Ni,Jia-Zuan, AU - He,Xiao-Yang, Y1 - 2015/11/20/ PY - 2015/03/31/received PY - 2015/09/18/revised PY - 2015/10/04/accepted PY - 2015/11/21/entrez PY - 2015/11/21/pubmed PY - 2016/10/19/medline KW - Alzheimer's disease KW - Icariin KW - Magnetic resonance spectroscopy KW - Mitochondrial dysfunction KW - N-acetylaspartate SP - 63 EP - 73 JF - CNS neuroscience & therapeutics JO - CNS Neurosci Ther VL - 22 IS - 1 N2 - AIMS: This study investigated the neuroprotective properties of icariin (an effective component of traditional Chinese herbal medicine Epimedium) on neuronal function and brain energy metabolism maintenance in a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD). METHODS: 3 × Tg-AD mice as well as primary neurons were subjected to icariin treatment. Morris water maze assay, magnetic resonance spectroscopy (MRS), Western blotting, ELISA, and immunohistochemistry analysis were used to evaluate the effects of icariin administration. RESULTS: Icariin significantly improved spatial learning and memory retention in 3 × Tg-AD mice, promoted neuronal cell activity as identified by the enhancement of brain metabolite N-acetylaspartate level and ATP production in AD mice, preserved the expressions of mitochondrial key enzymes COX IV, PDHE1α, and synaptic protein PSD95, reduced Aβ plaque deposition in the cortex and hippocampus of AD mice, and inhibited β-site APP cleavage enzyme 1 (BACE1) expression. Icariin treatment also decreased the levels of extracellular and intracellular Aβ1-42 in 3 × Tg-AD primary neurons, modulated the distribution of Aβ along the neurites, and protected against mitochondrial fragmentation in 3 × Tg-AD neurons. CONCLUSIONS: Icariin shows neuroprotective effects in 3 × Tg-AD mice and may be a promising multitarget drug in the prevention/protection against AD. SN - 1755-5949 UR - https://www.unboundmedicine.com/medline/citation/26584824/Neuroprotective_Effects_of_Icariin_on_Brain_Metabolism_Mitochondrial_Functions_and_Cognition_in_Triple_Transgenic_Alzheimer's_Disease_Mice_ L2 - https://doi.org/10.1111/cns.12473 DB - PRIME DP - Unbound Medicine ER -