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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

Aβ1-40 accumulation reduced by the fractions and flavonoids was differentially recovered by bacitracin. (a) swAPP770-transfected N2a cells were treated with the fractions and flavonoids for 20 h at NTC, in the absence (closed columns) and presence (opened columns) of 2 nM bacitracin. The level of extracellular Aβ1-40 was determined by ELISA. (b) The recovery effect of bacitracin was calculated by the subtraction between the levels of the cells treated with and without bacitracin. Results are means ± SD from three independent experiments. Significant differences between control and FM fractions-treated cells are indicated by ***P < 0.001.
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fig6: Aβ1-40 accumulation reduced by the fractions and flavonoids was differentially recovered by bacitracin. (a) swAPP770-transfected N2a cells were treated with the fractions and flavonoids for 20 h at NTC, in the absence (closed columns) and presence (opened columns) of 2 nM bacitracin. The level of extracellular Aβ1-40 was determined by ELISA. (b) The recovery effect of bacitracin was calculated by the subtraction between the levels of the cells treated with and without bacitracin. Results are means ± SD from three independent experiments. Significant differences between control and FM fractions-treated cells are indicated by ***P < 0.001.

Mentions: The promoting activity of the fractions and flavonoids on Aβ degradation by IDE may include bacitracin-sensitive and -insensitive pools. The bacitracin-sensitive pools in the cultures treated with the fraction EtOH, EA-74, B50M, and flavonoid 94-19-13 were 10.71, 10.83, 11.35, and 11.29 ng/mL, respectively (Figure 6). The results suggested that these treatments did not affect the bacitracin-sensitive pool. The bacitracin-sensitive pools in the cultures treated with the flavonoid 49-3 and 52-11 were 7.18 and 14.05 ng/mL, suggesting that flavonoid 49-3 and 52-11 reduce and enhance the bacitracin-sensitive pool, respectively.


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)

Aβ1-40 accumulation reduced by the fractions and flavonoids was differentially recovered by bacitracin. (a) swAPP770-transfected N2a cells were treated with the fractions and flavonoids for 20 h at NTC, in the absence (closed columns) and presence (opened columns) of 2 nM bacitracin. The level of extracellular Aβ1-40 was determined by ELISA. (b) The recovery effect of bacitracin was calculated by the subtraction between the levels of the cells treated with and without bacitracin. Results are means ± SD from three independent experiments. Significant differences between control and FM fractions-treated cells are indicated by ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Aβ1-40 accumulation reduced by the fractions and flavonoids was differentially recovered by bacitracin. (a) swAPP770-transfected N2a cells were treated with the fractions and flavonoids for 20 h at NTC, in the absence (closed columns) and presence (opened columns) of 2 nM bacitracin. The level of extracellular Aβ1-40 was determined by ELISA. (b) The recovery effect of bacitracin was calculated by the subtraction between the levels of the cells treated with and without bacitracin. Results are means ± SD from three independent experiments. Significant differences between control and FM fractions-treated cells are indicated by ***P < 0.001.
Mentions: The promoting activity of the fractions and flavonoids on Aβ degradation by IDE may include bacitracin-sensitive and -insensitive pools. The bacitracin-sensitive pools in the cultures treated with the fraction EtOH, EA-74, B50M, and flavonoid 94-19-13 were 10.71, 10.83, 11.35, and 11.29 ng/mL, respectively (Figure 6). The results suggested that these treatments did not affect the bacitracin-sensitive pool. The bacitracin-sensitive pools in the cultures treated with the flavonoid 49-3 and 52-11 were 7.18 and 14.05 ng/mL, suggesting that flavonoid 49-3 and 52-11 reduce and enhance the bacitracin-sensitive pool, respectively.

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