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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 learning and memory impairments in APP V717I transgenic mice (object recognition test, ORT). 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. Comparison of the discrimination index (DI) in different mice groups at 4 months of age and 10 months of age. B. Effects of icariin on DI in 10-month-old APP Tg mice. On day 2, there was no significant difference in the exploration time to 2 identical objects among groups. On day 3, there was no significant difference in total exploration time (N+F) among groups. n=18. The data are shown as mean ± SD; ▲P<0.05, compared with Tg(-) mice; △△P<0.01, compared with 4-month-old APP Tg mice; *P<0.05, compared with APP Tg(+) model mice.
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Figure 2: Effects of icariin on learning and memory impairments in APP V717I transgenic mice (object recognition test, ORT). 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. Comparison of the discrimination index (DI) in different mice groups at 4 months of age and 10 months of age. B. Effects of icariin on DI in 10-month-old APP Tg mice. On day 2, there was no significant difference in the exploration time to 2 identical objects among groups. On day 3, there was no significant difference in total exploration time (N+F) among groups. n=18. The data are shown as mean ± SD; ▲P<0.05, compared with Tg(-) mice; △△P<0.01, compared with 4-month-old APP Tg mice; *P<0.05, compared with APP Tg(+) model mice.

Mentions: In the object recognition test (ORT), there was no significant difference in the exploration time to 2 identical objects on day 2 among groups (data not shown). On day 3, 10-month-old Tg(+) mice showed a significant decrease in the memory discrimination index (DI) compared with both age-matched Tg(-) mice (P<0.05) and 4-month-old Tg(+) mice (P<0.01; Fig. 2A). The DI was significantly increased in mice that were treated with icariin (100 μmol/kg) for 6 months compared with the Tg(+) model mice (P<0.05), suggesting an improvement in object recognition memory by icariin treatment (Fig. 2B). There was no significant difference in total exploration time (N+F) that was observed among groups.


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 learning and memory impairments in APP V717I transgenic mice (object recognition test, ORT). 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. Comparison of the discrimination index (DI) in different mice groups at 4 months of age and 10 months of age. B. Effects of icariin on DI in 10-month-old APP Tg mice. On day 2, there was no significant difference in the exploration time to 2 identical objects among groups. On day 3, there was no significant difference in total exploration time (N+F) among groups. n=18. The data are shown as mean ± SD; ▲P<0.05, compared with Tg(-) mice; △△P<0.01, compared with 4-month-old APP Tg mice; *P<0.05, compared with APP Tg(+) model mice.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Effects of icariin on learning and memory impairments in APP V717I transgenic mice (object recognition test, ORT). 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. Comparison of the discrimination index (DI) in different mice groups at 4 months of age and 10 months of age. B. Effects of icariin on DI in 10-month-old APP Tg mice. On day 2, there was no significant difference in the exploration time to 2 identical objects among groups. On day 3, there was no significant difference in total exploration time (N+F) among groups. n=18. The data are shown as mean ± SD; ▲P<0.05, compared with Tg(-) mice; △△P<0.01, compared with 4-month-old APP Tg mice; *P<0.05, compared with APP Tg(+) model mice.
Mentions: In the object recognition test (ORT), there was no significant difference in the exploration time to 2 identical objects on day 2 among groups (data not shown). On day 3, 10-month-old Tg(+) mice showed a significant decrease in the memory discrimination index (DI) compared with both age-matched Tg(-) mice (P<0.05) and 4-month-old Tg(+) mice (P<0.01; Fig. 2A). The DI was significantly increased in mice that were treated with icariin (100 μmol/kg) for 6 months compared with the Tg(+) model mice (P<0.05), suggesting an improvement in object recognition memory by icariin treatment (Fig. 2B). There was no significant difference in total exploration time (N+F) that was observed among groups.

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