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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 LPS, IFN-γ, and IFN-γ + fAβ on nitric oxide production in BV-2 cells. BV-2 cells were treated with indicated concentrations of LPS (a, b) or vehicle, 0.1 and 0.2 ng/ml IFN-γ alone, vehicle or FN-γ + 1 μM fAβ (c, d), for 24 h. (a, c) After treatment, cultured medium was collected and the nitrite content was determined. (b, d) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between cells treated with vehicle (Veh) and LPS or IFN-γ is indicated by *, p < 0.05, ***, p < 0.001. Significant differences between the cells treated with IFN-γ alone and IFN-γ combined with fAβ are indicated by ###, p < 0.001.
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Figure 2: Effect of LPS, IFN-γ, and IFN-γ + fAβ on nitric oxide production in BV-2 cells. BV-2 cells were treated with indicated concentrations of LPS (a, b) or vehicle, 0.1 and 0.2 ng/ml IFN-γ alone, vehicle or FN-γ + 1 μM fAβ (c, d), for 24 h. (a, c) After treatment, cultured medium was collected and the nitrite content was determined. (b, d) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between cells treated with vehicle (Veh) and LPS or IFN-γ is indicated by *, p < 0.05, ***, p < 0.001. Significant differences between the cells treated with IFN-γ alone and IFN-γ combined with fAβ are indicated by ###, p < 0.001.

Mentions: To determine the inflammatory potential of BV-2 cells, nitric oxide production was assayed after BV-2 cells were activated by different stimuli. LPS at 2 and 10 ng/ml stimulate BV-2 to produce 2.83 ± 0.54 and 5.52 ± 0.12 nmol/well nitric oxide, respectively, without significantly affect the cell viability (Figure 2a, b). IFN-γ at 0.1 and 0.2 ng/ml stimulates BV-2 to produce 1.27 ± 0.10 and 2.88 ± 0.07 nmol/well nitric oxide, respectively. As combined with 1 μM fAβ, the production of 0.1 and 0.2 ng/ml IFN-γ-stimulated nitric oxide productions were increased to 2.20 ± 0.22 and 4.46 ± 0.49 nmol/well, respectively (Figure 2c). The cell viability is also not affected by IFN-γ (Figure 2d). However, oAβ failed to enhance the IFN-γ-stimulated production of nitric oxide (data not shown).


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 LPS, IFN-γ, and IFN-γ + fAβ on nitric oxide production in BV-2 cells. BV-2 cells were treated with indicated concentrations of LPS (a, b) or vehicle, 0.1 and 0.2 ng/ml IFN-γ alone, vehicle or FN-γ + 1 μM fAβ (c, d), for 24 h. (a, c) After treatment, cultured medium was collected and the nitrite content was determined. (b, d) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between cells treated with vehicle (Veh) and LPS or IFN-γ is indicated by *, p < 0.05, ***, p < 0.001. Significant differences between the cells treated with IFN-γ alone and IFN-γ combined with fAβ 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 2: Effect of LPS, IFN-γ, and IFN-γ + fAβ on nitric oxide production in BV-2 cells. BV-2 cells were treated with indicated concentrations of LPS (a, b) or vehicle, 0.1 and 0.2 ng/ml IFN-γ alone, vehicle or FN-γ + 1 μM fAβ (c, d), for 24 h. (a, c) After treatment, cultured medium was collected and the nitrite content was determined. (b, d) The cell viability of the treated cells was assayed by MTT reduction. Results are means ± S.D. from three independent experiments. Significant differences between cells treated with vehicle (Veh) and LPS or IFN-γ is indicated by *, p < 0.05, ***, p < 0.001. Significant differences between the cells treated with IFN-γ alone and IFN-γ combined with fAβ are indicated by ###, p < 0.001.
Mentions: To determine the inflammatory potential of BV-2 cells, nitric oxide production was assayed after BV-2 cells were activated by different stimuli. LPS at 2 and 10 ng/ml stimulate BV-2 to produce 2.83 ± 0.54 and 5.52 ± 0.12 nmol/well nitric oxide, respectively, without significantly affect the cell viability (Figure 2a, b). IFN-γ at 0.1 and 0.2 ng/ml stimulates BV-2 to produce 1.27 ± 0.10 and 2.88 ± 0.07 nmol/well nitric oxide, respectively. As combined with 1 μM fAβ, the production of 0.1 and 0.2 ng/ml IFN-γ-stimulated nitric oxide productions were increased to 2.20 ± 0.22 and 4.46 ± 0.49 nmol/well, respectively (Figure 2c). The cell viability is also not affected by IFN-γ (Figure 2d). However, oAβ failed to enhance the IFN-γ-stimulated production of nitric oxide (data not shown).

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