The Isolated and Combined Effects of Folic Acid and Synthetic Bioactive Compounds against Aβ(_25-35)-Induced Toxicity in Human Microglial Cells

Abstract: Folic acid plays an important role in neuronal development. A series of newly synthesized bioactive compounds (NSCs) was reported to exhibit immunoactive and neuroprotective functions. The isolated and combined effects of folic acid and NSCs against β-amyloid (Aβ)-induced cytotoxicity are poorly understood. These effects were tested using human microglia cells (C13NJ) subjected to Aβ_(25-35) challenge. According to an MTT assay, treatment of C13NJ cells with Aβ_(25-35) at 10~100 μM for 48 h induced 18%~43% cellular death in a dose-dependent manner (p < 0.05). Aβ_(25-35) treatment at 25 μM induced nitrite oxide (NO) release, elevated superoxide production, and reduced the distribution of cells in the S phase. Preincubation of C13NJ with 100 μM folic acid protected against Aβ_(25-35)-induced cell death, which coincided with a reduction in NO release by folic acid supplements. NSC47 at a level of 50 μM protected against Aβ_(25-35)-induced cell death and reduced Aβ-promoted superoxide production (p < 0.05). Folic acid in combination with NSC47 at their cytoprotective doses did not synergistically ameliorate Aβ_(25-35)-associated NO release, superoxide production, or cell cycle arrest. Taken together, folic acid or NSC treatment alone, but not the combined regimen, protected against Aβ_(25-35)-induced cell death, which may partially, if not completely, be mediated by free radical-scavenging effects.