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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

The structure of the compounds and the amyloid peptides used in this study. (a) The structure and chemical name of the compounds isolated from C. cochinchinesis. (b) The representing images of the conformation of the prepared Aβ aggregates.
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Figure 1: The structure of the compounds and the amyloid peptides used in this study. (a) The structure and chemical name of the compounds isolated from C. cochinchinesis. (b) The representing images of the conformation of the prepared Aβ aggregates.

Mentions: The extraction of C. cochinchinensis were processed according to the method previously described [2]. Briefly, the air-dried roots of C. cochinchinensis were extracted four times with methanol (MeOH) under reflux to give the MeOH extract. The MeOH extract was partitioned with an ethyl acetate (EtOAc) and water mixture (1:1) to give the EtOAc extract and the water extract (CC-EW). The EtOAc extract was subjected to silica gel column chromatography eluting with n-hexane: EtOAc/MeOH to give eight fractions. Fractions was further separated by HPLC (Cosmosil 5C18-AR, Nacalai Tesque, Tokyo, Janpan) to obtain CCA to CCF. The structure of each compound (Figure 1a) was elucidated with mass and NMR spectroscopy in comparison to the published data. The purity of each compound was >98% as judged by HPLC and 1H NMR.


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)

The structure of the compounds and the amyloid peptides used in this study. (a) The structure and chemical name of the compounds isolated from C. cochinchinesis. (b) The representing images of the conformation of the prepared Aβ aggregates.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The structure of the compounds and the amyloid peptides used in this study. (a) The structure and chemical name of the compounds isolated from C. cochinchinesis. (b) The representing images of the conformation of the prepared Aβ aggregates.
Mentions: The extraction of C. cochinchinensis were processed according to the method previously described [2]. Briefly, the air-dried roots of C. cochinchinensis were extracted four times with methanol (MeOH) under reflux to give the MeOH extract. The MeOH extract was partitioned with an ethyl acetate (EtOAc) and water mixture (1:1) to give the EtOAc extract and the water extract (CC-EW). The EtOAc extract was subjected to silica gel column chromatography eluting with n-hexane: EtOAc/MeOH to give eight fractions. Fractions was further separated by HPLC (Cosmosil 5C18-AR, Nacalai Tesque, Tokyo, Janpan) to obtain CCA to CCF. The structure of each compound (Figure 1a) was elucidated with mass and NMR spectroscopy in comparison to the published data. The purity of each compound was >98% as judged by HPLC and 1H NMR.

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