Ellagic Acid Protects against Activation of Microglia by Inhibiting MAPKs and NF-κB Signalling

Context: One of the hallmarks of neurodegenerative diseases is dysregulation of microglia resulting in neuroinflammation. Neuroinflammation is related to multiple neurodegenerative disorders, including stroke and Alzheimer’s disease. Ellagic acid (EA) possesses antiapoptotic activity, anti-inflammatory, and antioxidant properties. It is most commonly found in fruits and nuts. EA has been linked to neuronal protection particularly through its anti-inflammatory and antioxidant actions. For example, EA inhibits enzyme activity which prevents the onset of Alzheimer’s disease. Aim: In this study, the underlying protective mechanisms of EA in LPS-activated BV2 cells were investigated. Settings and Design: EA prepared in multiple concentrations was introduced for 24 hrs as pre-treatment in BV2 microglial cells. Lipopolysaccharide (LPS) at 1 μg mL-1 was used to stimulate BV2 microglial cells after the EA pre-treatment for an additional 24 hrs. After 24 hrs of stimulation, the cell lysate was harvested for bioassays. Materials and Methods: This study investigated the effects of EA on the viability of BV2 microglial cells using MTT assay. After LPS stimulation, the cell lysate was collected to measure nitric oxide (NO) levels using Griess assay kit and ELISA was used to measure TNFα levels. Western blotting was used to test protein levels of iNOS, MyD88, MAPKs and NF-κB. Statistical analysis used: Data are provided as means and standard errors of n = 3. A one-way analysis of variance was used to test the statistical significance of between group comparisons. The statistical significance of p<0.05 was set. Results: EA decreased the levels of TNFα and NO production in BV2 microglial cells induced by LPS. EA also reduced inducible nitric oxide synthase (iNOS) expression, and attenuated MyD88 and NF-κB expression. EA decreased the phosphorylation of p38, ERK and JNK and repressed the activation of CD11b and CD40 in a concentration-dependent manner. Conclusion: EA has a putative role in preventing neuroinflammation but its application in prevention of neurodegenerative diseases requires further investigations.