Effects of icariin on Aβ contents in the hippocampus o

Icariin decreases the expression of APP and BACE-1 and reduces the β-amyloid burden in an APP transgenic mouse model of Alzheimer's disease. Zhang L, Shen C, Chu J, Zhang R, Li Y, Li L - Int. J. Biol. Sci. (2014) Bottom Line: The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry.The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus.These novel findings suggest that icariin may be a promising treatment in patients with AD. View Article: PubMed Central - PubMed Affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China. ABSTRACT Objective: The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD). Methods: APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry. Results: Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. Conclusion: Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD. Show MeSH Major Amyloid Precursor Protein Secretases/genetics/metabolism* Amyloid beta-Protein Precursor/genetics/metabolism* Aspartic Acid Endopeptidases/genetics/metabolism* Flavonoids/pharmacology/therapeutic use Plaque, Amyloid/drug therapy Minor Alzheimer Disease/metabolism/pathology Animals Hippocampus/metabolism/pathology Humans Learning Disorders/drug therapy/metabolism Memory Disorders/drug therapy/metabolism Mice Mice, Inbred C57BL Mice, Transgenic Related in: MedlinePlus	© Copyright Policy Related In: Results - Collection Show All Figures getmorefigures.php?uid=PMC3927130&req=5 Figure 3: Effects of icariin on Aβ contents in the hippocampus of 10-month-old APP V717I transgenic mice. Icariin (ICA) at the doses of 30 μmol/kg (L) and 100 μmol/kg (H) was intragastrically administered to APP Tg mice for 6 months (from 4 to 10 months of age). A. Aβ burden in the hippocampal CA1 region that was detected with immunohistochemical staining by using anti-Aβ1-16 antibody (scale bar = 50 μm). n=5. B. Aβ1-42 contents in the whole hippocampus that were measured with enzyme-linked immunosorbent assays. n=8-10. The data are shown as mean ± SD; ▲▲P < 0.01, compared with Tg(-) mice; P < 0.01, compared with Tg(+) model mice. Mentions:** The immunohistochemical staining with the anti-Aβ1-16 was used to evaluate the total Aβ burden in mouse brain. The number of Aβ-positive cells was significantly increased in the hippocampal CA1 region of Tg(+) mice at the age of 10 months compared with that in the age-matched Tg(-) control group. Tg(+) mice that were treated with 100 μmol/kg icariin showed an obvious decrease in the number of Aβ-positive cells compared with that in the Tg(+) model mice (Fig. 3A).

Icariin decreases the expression of APP and BACE-1 and reduces the β-amyloid burden in an APP transgenic mouse model of Alzheimer's disease.

Zhang L, Shen C, Chu J, Zhang R, Li Y, Li L - Int. J. Biol. Sci. (2014)

Bottom Line: The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry.The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus.These novel findings suggest that icariin may be a promising treatment in patients with AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.

ABSTRACT

Objective: The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD).

Methods: APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry.

Results: Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus.

Conclusion: Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD.

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Related in: MedlinePlus

Effects of icariin on Aβ contents in the hippocampus of 10-month-old APP V717I transgenic mice. Icariin (ICA) at the doses of 30 μmol/kg (L) and 100 μmol/kg (H) was intragastrically administered to APP Tg mice for 6 months (from 4 to 10 months of age). A. Aβ burden in the hippocampal CA1 region that was detected with immunohistochemical staining by using anti-Aβ1-16 antibody (scale bar = 50 μm). n=5. B. Aβ1-42 contents in the whole hippocampus that were measured with enzyme-linked immunosorbent assays. n=8-10. The data are shown as mean ± SD; ▲▲P < 0.01, compared with Tg(-) mice; ** P < 0.01, compared with Tg(+) model mice.

Related In: Results - Collection

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Figure 3: Effects of icariin on Aβ contents in the hippocampus of 10-month-old APP V717I transgenic mice. Icariin (ICA) at the doses of 30 μmol/kg (L) and 100 μmol/kg (H) was intragastrically administered to APP Tg mice for 6 months (from 4 to 10 months of age). A. Aβ burden in the hippocampal CA1 region that was detected with immunohistochemical staining by using anti-Aβ1-16 antibody (scale bar = 50 μm). n=5. B. Aβ1-42 contents in the whole hippocampus that were measured with enzyme-linked immunosorbent assays. n=8-10. The data are shown as mean ± SD; ▲▲P < 0.01, compared with Tg(-) mice; ** P < 0.01, compared with Tg(+) model mice.

Mentions: The immunohistochemical staining with the anti-Aβ1-16 was used to evaluate the total Aβ burden in mouse brain. The number of Aβ-positive cells was significantly increased in the hippocampal CA1 region of Tg(+) mice at the age of 10 months compared with that in the age-matched Tg(-) control group. Tg(+) mice that were treated with 100 μmol/kg icariin showed an obvious decrease in the number of Aβ-positive cells compared with that in the Tg(+) model mice (Fig. 3A).