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Published on:JANUARY 2018
Indian Journal of Pharmaceutical Education and Research, 2018; 52(1):32-41
Original Article | doi:10.5530/ijper.52.1.4

Curcumin: The Molecular Mechanisms of Action in Inflammation and Cell Death during Kainate-Induced Epileptogenesis


Authors and affiliation (s):

Yow Hui-Yin1, Nurulumi Ahmad2, Norazrina Azmi2, Mohd Makmor-Bakry2*

1School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University Lakeside Campus, Subang Jaya, MALAYSIA.

2Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, MALAYSIA.

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 KAinduced epileptogenesis. Inflammation and immune response were the prominent overexpressed 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.

Key words: Epileptogenesis, Curcumin, Kainic acid, Gene expression, Anti-epileptogenic, Temporal lobe epilepsy.

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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