Curcumin: The molecular mechanisms of action in inflammation and cell death during kainate-induced epileptogenesis

Abstract

Background: Recent preclinical studies demonstrated the potential antiepileptogenic effect of curcumin. Its molecular pathways in modulating epileptogenesis remain unclear. Objectives: This study investigated the epileptogenic processes induced by kainic acid (KA) and to investigate the antiepileptogenic pathways associated with curcumin therapy. Methods: A single dose of KA 10 mg/kg was used to induce a convulsive status epilepticus in female Wistar rats. After one week of curcumin treatment, gene expression profiling by using microarray was conducted on hippocampal tissues. A set of differential expression changes was determined based on criteria of dual fold change in either direction and p < 0.05, whereas gene annotation and pathway analysis had been performed using Database for Annotation, Visualization and Integrated Discovery software. Results: A number of genes significantly altered in expression during KA-induced epileptogenesis. Inflammation and immune response were the prominent over-expressed processes induced by KA. Genes of cell surface molecule (CD74), cytokines and immune response related genes (IL18, IFNGR1, C3, RT1-BA) were significantly up-regulated. Changes of genes related to cell death and gliosis (NCSTN, CTSH) were also observed in KA-induced epileptogenesis. This study revealed that curcumin modulated the epileptogenic process by up-regulating genes related to antiinflammatory cytokines (IL10RB, CXCL16, and CXCL17) and protecting against cell loss by up-regulating NCSTN. It was also likely to exert neuroprotective effects through the up-regulation of CX3CL1 and CXCL16. Conclusion: This study provides novel insights into the mechanisms of curcumin in epileptic brain, which form the basis for future studies looking into its molecular pathway as an antiepileptogenic agent.