RESUMEN
BACKGROUND: Microglial inflammation may significantly contribute to the pathology of Alzheimer's disease. To examine the potential of Cudrania cochinchinensis to ameliorate amyloid ß protein (Aß)-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 Aß (fAß), or oligomeric Aß (oAß) were used to activate microglia. LPS and IFN-γ, but not Aßs, 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. fAß, but not oAß, 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 fAß. On the other hand, oAß 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 Aß-mediated morphological change of microglia. Furthermore, CC-EW and CCB effectively decreased Aß deposition and remained Aß in the conditioned medium suggesting the effect of CC-EW and CCB on promoting Aß 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.