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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 amyloid plaques 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. Congo red staining. B. Semiquantitative analysis of Congo red staining. C. Bielschowsky silver staining. n=5. The data are shown as mean ± SD; ▲▲P<0.01, compared with Tg(-) mice; **P<0.01, compared with APP Tg(+) model mice. Scale bar = 50 μm.
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Figure 4: Effects of icariin on amyloid plaques 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. Congo red staining. B. Semiquantitative analysis of Congo red staining. C. Bielschowsky silver staining. n=5. The data are shown as mean ± SD; ▲▲P<0.01, compared with Tg(-) mice; **P<0.01, compared with APP Tg(+) model mice. Scale bar = 50 μm.

Mentions: Congo red was used to stain the amyloid plaques in the brains of mice, and the positively stained areas were measured with an image analysis system in order to determine the quantity of amyloid plaques. The results showed that amyloid plaques were scattered in the molecular/polymorphic layer of the hippocampus, and rare amyloid plaques were distributed in the pyramidal cell layer. The amyloid plaques exhibited a light red dispersion without distinct boundaries, and plaque staining was denser in the hippocampus of Tg(+) mice (Fig. 4A). The molecular layer in the hippocampi of 10-month-old Tg(+) mice had a larger percentage of areas that were positive for amyloid plaques than the age-matched Tg(-) control group (P < 0.01). After icariin (30 and 100 μmol/kg) administration for 6 months, the plaque staining was lighter, and the positively stained areas of amyloid plaques were significantly reduced (P < 0.01) (Fig. 4B).


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)

Effects of icariin on amyloid plaques 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. Congo red staining. B. Semiquantitative analysis of Congo red staining. C. Bielschowsky silver staining. n=5. The data are shown as mean ± SD; ▲▲P<0.01, compared with Tg(-) mice; **P<0.01, compared with APP Tg(+) model mice. Scale bar = 50 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3927130&req=5

Figure 4: Effects of icariin on amyloid plaques 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. Congo red staining. B. Semiquantitative analysis of Congo red staining. C. Bielschowsky silver staining. n=5. The data are shown as mean ± SD; ▲▲P<0.01, compared with Tg(-) mice; **P<0.01, compared with APP Tg(+) model mice. Scale bar = 50 μm.
Mentions: Congo red was used to stain the amyloid plaques in the brains of mice, and the positively stained areas were measured with an image analysis system in order to determine the quantity of amyloid plaques. The results showed that amyloid plaques were scattered in the molecular/polymorphic layer of the hippocampus, and rare amyloid plaques were distributed in the pyramidal cell layer. The amyloid plaques exhibited a light red dispersion without distinct boundaries, and plaque staining was denser in the hippocampus of Tg(+) mice (Fig. 4A). The molecular layer in the hippocampi of 10-month-old Tg(+) mice had a larger percentage of areas that were positive for amyloid plaques than the age-matched Tg(-) control group (P < 0.01). After icariin (30 and 100 μmol/kg) administration for 6 months, the plaque staining was lighter, and the positively stained areas of amyloid plaques were significantly reduced (P < 0.01) (Fig. 4B).

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
Related in: MedlinePlus