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The Components of Flemingia macrophylla Attenuate Amyloid β-Protein Accumulation by Regulating Amyloid β-Protein Metabolic Pathway.

Lin YL, Tsay HJ, Liao YF, Wu MF, Wang CN, Shiao YJ - Evid Based Complement Alternat Med (2012)

Bottom Line: Therefore, the effects of F. macrophylla on Aβ production and degradation were studied.The effect of F. macrophylla on Aβ metabolism was detected using the cultured mouse neuroblastoma cells N2a transfected with human Swedish mutant APP (swAPP-N2a cells).The effects on Aβ degradation were evaluated on a cell-free system.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei 112, Taiwan.

ABSTRACT
Flemingia macrophylla (Leguminosae) is a popular traditional remedy used in Taiwan as anti-inflammatory, promoting blood circulation and antidiabetes agent. Recent study also suggested its neuroprotective activity against Alzheimer's disease. Therefore, the effects of F. macrophylla on Aβ production and degradation were studied. The effect of F. macrophylla on Aβ metabolism was detected using the cultured mouse neuroblastoma cells N2a transfected with human Swedish mutant APP (swAPP-N2a cells). The effects on Aβ degradation were evaluated on a cell-free system. An ELISA assay was applied to detect the level of Aβ1-40 and Aβ1-42. Western blots assay was employed to measure the levels of soluble amyloid precursor protein and insulin degrading enzyme (IDE). Three fractions of F. macrophylla modified Aβ accumulation by both inhibiting β-secretase and activating IDE. Three flavonoids modified Aβ accumulation by activating IDE. The activated IDE pool by the flavonoids was distinctly regulated by bacitracin (an IDE inhibitor). Furthermore, flavonoid 94-18-13 also modulates Aβ accumulation by enhancing IDE expression. In conclusion, the components of F. macrophylla possess the potential for developing new therapeutic drugs for Alzheimer's disease.

No MeSH data available.


Related in: MedlinePlus

The level of IDE was differentially affected by the fractions and flavonoids of F. macrophylla. N2a cells were treated with fractions and flavonoids for 20 h at NTC. The level of IDE in cell lysate and medium was determined by immunoblotting. The upper panel is the representative blot. The lower panel is the relative level of IDE in cell lysate (closed column) and medium (opened column) exhibited as percentage of the control. Results are means ± SD from three independent experiments. Significant differences between control and the treated cells are indicated by *P < 0.05, **P < 0.01 and ***P < 0.001.
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fig5: The level of IDE was differentially affected by the fractions and flavonoids of F. macrophylla. N2a cells were treated with fractions and flavonoids for 20 h at NTC. The level of IDE in cell lysate and medium was determined by immunoblotting. The upper panel is the representative blot. The lower panel is the relative level of IDE in cell lysate (closed column) and medium (opened column) exhibited as percentage of the control. Results are means ± SD from three independent experiments. Significant differences between control and the treated cells are indicated by *P < 0.05, **P < 0.01 and ***P < 0.001.

Mentions: Treatment with the fraction B50M, EA-74, and flavonoid 49-2, 52-11, and 94-18-13 attenuated the level of cellular IDE by about 20%, whereas the fraction EtOH failed to show significant effect on the level of cellular IDE (Figure 5). Treatment with the faction B50M and EA-74 eliminated the level of medial IDE by 21.3 ± 12.0 and 26.6 ± 9.9%, respectively. On the contrary, flavonoid 94-18-13 increased the level of medial IDE to 146.9 ± 16.7% of the control. The result suggested that only flavonoid 94-18-13 may accelerate Aβ degradation by promoting IDE expression. The change in enzyme activity may also be involved although it is not detected in this study.


The Components of Flemingia macrophylla Attenuate Amyloid β-Protein Accumulation by Regulating Amyloid β-Protein Metabolic Pathway.

Lin YL, Tsay HJ, Liao YF, Wu MF, Wang CN, Shiao YJ - Evid Based Complement Alternat Med (2012)

The level of IDE was differentially affected by the fractions and flavonoids of F. macrophylla. N2a cells were treated with fractions and flavonoids for 20 h at NTC. The level of IDE in cell lysate and medium was determined by immunoblotting. The upper panel is the representative blot. The lower panel is the relative level of IDE in cell lysate (closed column) and medium (opened column) exhibited as percentage of the control. Results are means ± SD from three independent experiments. Significant differences between control and the treated cells are indicated by *P < 0.05, **P < 0.01 and ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376484&req=5

fig5: The level of IDE was differentially affected by the fractions and flavonoids of F. macrophylla. N2a cells were treated with fractions and flavonoids for 20 h at NTC. The level of IDE in cell lysate and medium was determined by immunoblotting. The upper panel is the representative blot. The lower panel is the relative level of IDE in cell lysate (closed column) and medium (opened column) exhibited as percentage of the control. Results are means ± SD from three independent experiments. Significant differences between control and the treated cells are indicated by *P < 0.05, **P < 0.01 and ***P < 0.001.
Mentions: Treatment with the fraction B50M, EA-74, and flavonoid 49-2, 52-11, and 94-18-13 attenuated the level of cellular IDE by about 20%, whereas the fraction EtOH failed to show significant effect on the level of cellular IDE (Figure 5). Treatment with the faction B50M and EA-74 eliminated the level of medial IDE by 21.3 ± 12.0 and 26.6 ± 9.9%, respectively. On the contrary, flavonoid 94-18-13 increased the level of medial IDE to 146.9 ± 16.7% of the control. The result suggested that only flavonoid 94-18-13 may accelerate Aβ degradation by promoting IDE expression. The change in enzyme activity may also be involved although it is not detected in this study.

Bottom Line: Therefore, the effects of F. macrophylla on Aβ production and degradation were studied.The effect of F. macrophylla on Aβ metabolism was detected using the cultured mouse neuroblastoma cells N2a transfected with human Swedish mutant APP (swAPP-N2a cells).The effects on Aβ degradation were evaluated on a cell-free system.

View Article: PubMed Central - PubMed

Affiliation: Division of Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei 112, Taiwan.

ABSTRACT
Flemingia macrophylla (Leguminosae) is a popular traditional remedy used in Taiwan as anti-inflammatory, promoting blood circulation and antidiabetes agent. Recent study also suggested its neuroprotective activity against Alzheimer's disease. Therefore, the effects of F. macrophylla on Aβ production and degradation were studied. The effect of F. macrophylla on Aβ metabolism was detected using the cultured mouse neuroblastoma cells N2a transfected with human Swedish mutant APP (swAPP-N2a cells). The effects on Aβ degradation were evaluated on a cell-free system. An ELISA assay was applied to detect the level of Aβ1-40 and Aβ1-42. Western blots assay was employed to measure the levels of soluble amyloid precursor protein and insulin degrading enzyme (IDE). Three fractions of F. macrophylla modified Aβ accumulation by both inhibiting β-secretase and activating IDE. Three flavonoids modified Aβ accumulation by activating IDE. The activated IDE pool by the flavonoids was distinctly regulated by bacitracin (an IDE inhibitor). Furthermore, flavonoid 94-18-13 also modulates Aβ accumulation by enhancing IDE expression. In conclusion, the components of F. macrophylla possess the potential for developing new therapeutic drugs for Alzheimer's disease.

No MeSH data available.


Related in: MedlinePlus