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Cudrania cochinchinensis attenuates amyloid β protein-mediated microglial activation and promotes glia-related clearance of amyloid β protein.

Wang CJ, Chen CC, Tsay HJ, Chiang FY, Wu MF, Shiao YJ - J. Biomed. Sci. (2013)

Bottom Line: LPS and IFN-γ, but not Aβs, activated BV-2 cells to produce nitric oxide through an increase in inducible nitric oxide synthase (iNOS) expression without significant effects on cell viability of microglia. fAβ, but not oAβ, enhanced the IFN-γ-stimulated nitric oxide production and iNOS expression.The ethanol/water extracts of Cudrania cochinchinensis (CC-EW) and the purified isolated components (i.e. CCA to CCF) effectively reduced the nitric oxide production and iNOS expression stimulated by IFN-γ combined with fAβ.CC-EW and CCB effectively prohibit the Aβ-mediated morphological change of microglia.Furthermore, CC-EW and CCB effectively decreased Aβ deposition and remained Aβ in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aβ clearance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Geriatrics, Cheng Hsin General Hospital, Taipei, Taiwan.

ABSTRACT

Background: Microglial inflammation may significantly contribute to the pathology of Alzheimer's disease. To examine the potential of Cudrania cochinchinensis to ameliorate amyloid β protein (Aβ)-induced microglia activation, BV-2 microglial cell line, and the ramified microglia in the primary glial mixed cultured were employed.

Results: Lipopolysaccharide (LPS), Interferon-γ (IFN-γ), fibrillary Aβ (fAβ), or oligomeric Aβ (oAβ) were used to activate microglia. LPS and IFN-γ, but not Aβs, activated BV-2 cells to produce nitric oxide through an increase in inducible nitric oxide synthase (iNOS) expression without significant effects on cell viability of microglia. fAβ, but not oAβ, enhanced the IFN-γ-stimulated nitric oxide production and iNOS expression.The ethanol/water extracts of Cudrania cochinchinensis (CC-EW) and the purified isolated components (i.e. CCA to CCF) effectively reduced the nitric oxide production and iNOS expression stimulated by IFN-γ combined with fAβ. On the other hand, oAβ effectively activated the ramified microglia in mixed glial culture by observing the morphological alteration of the microglia from ramified to amoeboid. CC-EW and CCB effectively prohibit the Aβ-mediated morphological change of microglia. Furthermore, CC-EW and CCB effectively decreased Aβ deposition and remained Aβ in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aβ clearance. Results are expressed as mean ± S.D. and were analyzed by ANOVA with post-hoc multiple comparisons with a Bonferroni test.

Conclusions: The components of Cudrania cochinchinensis including CC-EW and CCB are potential for novel therapeutic intervention for Alzheimer's disease.

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Related in: MedlinePlus

Effect of Cudrania cochinchinensis on nitric oxide production induced by IFN-γ, fAβ and LPS in BV-2 cells. BV-2 cells were treated with indicated concentration of CC-EW (a, b, e, f), 20 μM of CCA to CCF (c, d) or indicated concentration of CCB for 2 h, and then treated with 0.2 ng/ml IFN-γ alone, IFN-γ combined with 1 μM fAβ or 10 ng/ml LPS for 24 h. (a, c, e) After treatment, the cultured medium was collected and the nitrite content was determined. (b, d, f) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between the cells treated with vehicle (Veh) and CC-EW or the compound, CCA to CCF, are indicated by ***, p < 0.001.
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Figure 3: Effect of Cudrania cochinchinensis on nitric oxide production induced by IFN-γ, fAβ and LPS in BV-2 cells. BV-2 cells were treated with indicated concentration of CC-EW (a, b, e, f), 20 μM of CCA to CCF (c, d) or indicated concentration of CCB for 2 h, and then treated with 0.2 ng/ml IFN-γ alone, IFN-γ combined with 1 μM fAβ or 10 ng/ml LPS for 24 h. (a, c, e) After treatment, the cultured medium was collected and the nitrite content was determined. (b, d, f) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between the cells treated with vehicle (Veh) and CC-EW or the compound, CCA to CCF, are indicated by ***, p < 0.001.

Mentions: To determine the anti-inflammatory effects of CC-EW, IFN-γ (0.2 ng/ml) alone or combined with fAβ (1 μM) were used as stimuli. CC-EW (20 μg/ml) reduced the nitric oxide production mediated by IFN-γ alone and combined with fAβ to 26.95 ± 4.79% and 53.79 ± 7.68% of the vehicle treated control cells, respectively (Figure 3a). The IC50 of CC-EW on the cells stimulated with IFN-γ alone and combined with fAβ was 58.28 ± 6.72 and 12.83 ± 3.36 μg/ml, respectively (Table 1), to suggest that CC-EW possess a higher inhibitory activity specifically to the stimulation by IFN-γ combined with fAβ than that by IFN-γ alone. On the contrary, CC-EW did not inhibit the stimulation by LPS (10 μg/ml) (Figure 3e). On the other hand, CC-EW in the concentration below 100 μg/ml did not significantly affect the viability of BV-2 cells (Figure 3d, f).


Cudrania cochinchinensis attenuates amyloid β protein-mediated microglial activation and promotes glia-related clearance of amyloid β protein.

Wang CJ, Chen CC, Tsay HJ, Chiang FY, Wu MF, Shiao YJ - J. Biomed. Sci. (2013)

Effect of Cudrania cochinchinensis on nitric oxide production induced by IFN-γ, fAβ and LPS in BV-2 cells. BV-2 cells were treated with indicated concentration of CC-EW (a, b, e, f), 20 μM of CCA to CCF (c, d) or indicated concentration of CCB for 2 h, and then treated with 0.2 ng/ml IFN-γ alone, IFN-γ combined with 1 μM fAβ or 10 ng/ml LPS for 24 h. (a, c, e) After treatment, the cultured medium was collected and the nitrite content was determined. (b, d, f) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between the cells treated with vehicle (Veh) and CC-EW or the compound, CCA to CCF, are indicated by ***, p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750318&req=5

Figure 3: Effect of Cudrania cochinchinensis on nitric oxide production induced by IFN-γ, fAβ and LPS in BV-2 cells. BV-2 cells were treated with indicated concentration of CC-EW (a, b, e, f), 20 μM of CCA to CCF (c, d) or indicated concentration of CCB for 2 h, and then treated with 0.2 ng/ml IFN-γ alone, IFN-γ combined with 1 μM fAβ or 10 ng/ml LPS for 24 h. (a, c, e) After treatment, the cultured medium was collected and the nitrite content was determined. (b, d, f) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between the cells treated with vehicle (Veh) and CC-EW or the compound, CCA to CCF, are indicated by ***, p < 0.001.
Mentions: To determine the anti-inflammatory effects of CC-EW, IFN-γ (0.2 ng/ml) alone or combined with fAβ (1 μM) were used as stimuli. CC-EW (20 μg/ml) reduced the nitric oxide production mediated by IFN-γ alone and combined with fAβ to 26.95 ± 4.79% and 53.79 ± 7.68% of the vehicle treated control cells, respectively (Figure 3a). The IC50 of CC-EW on the cells stimulated with IFN-γ alone and combined with fAβ was 58.28 ± 6.72 and 12.83 ± 3.36 μg/ml, respectively (Table 1), to suggest that CC-EW possess a higher inhibitory activity specifically to the stimulation by IFN-γ combined with fAβ than that by IFN-γ alone. On the contrary, CC-EW did not inhibit the stimulation by LPS (10 μg/ml) (Figure 3e). On the other hand, CC-EW in the concentration below 100 μg/ml did not significantly affect the viability of BV-2 cells (Figure 3d, f).

Bottom Line: LPS and IFN-γ, but not Aβs, activated BV-2 cells to produce nitric oxide through an increase in inducible nitric oxide synthase (iNOS) expression without significant effects on cell viability of microglia. fAβ, but not oAβ, enhanced the IFN-γ-stimulated nitric oxide production and iNOS expression.The ethanol/water extracts of Cudrania cochinchinensis (CC-EW) and the purified isolated components (i.e. CCA to CCF) effectively reduced the nitric oxide production and iNOS expression stimulated by IFN-γ combined with fAβ.CC-EW and CCB effectively prohibit the Aβ-mediated morphological change of microglia.Furthermore, CC-EW and CCB effectively decreased Aβ deposition and remained Aβ in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aβ clearance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Geriatrics, Cheng Hsin General Hospital, Taipei, Taiwan.

ABSTRACT

Background: Microglial inflammation may significantly contribute to the pathology of Alzheimer's disease. To examine the potential of Cudrania cochinchinensis to ameliorate amyloid β protein (Aβ)-induced microglia activation, BV-2 microglial cell line, and the ramified microglia in the primary glial mixed cultured were employed.

Results: Lipopolysaccharide (LPS), Interferon-γ (IFN-γ), fibrillary Aβ (fAβ), or oligomeric Aβ (oAβ) were used to activate microglia. LPS and IFN-γ, but not Aβs, activated BV-2 cells to produce nitric oxide through an increase in inducible nitric oxide synthase (iNOS) expression without significant effects on cell viability of microglia. fAβ, but not oAβ, enhanced the IFN-γ-stimulated nitric oxide production and iNOS expression.The ethanol/water extracts of Cudrania cochinchinensis (CC-EW) and the purified isolated components (i.e. CCA to CCF) effectively reduced the nitric oxide production and iNOS expression stimulated by IFN-γ combined with fAβ. On the other hand, oAβ effectively activated the ramified microglia in mixed glial culture by observing the morphological alteration of the microglia from ramified to amoeboid. CC-EW and CCB effectively prohibit the Aβ-mediated morphological change of microglia. Furthermore, CC-EW and CCB effectively decreased Aβ deposition and remained Aβ in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aβ clearance. Results are expressed as mean ± S.D. and were analyzed by ANOVA with post-hoc multiple comparisons with a Bonferroni test.

Conclusions: The components of Cudrania cochinchinensis including CC-EW and CCB are potential for novel therapeutic intervention for Alzheimer's disease.

Show MeSH
Related in: MedlinePlus