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

Yow Hui-Yin, Nurulumi Ahmad, Norazrina Azmi, Mohd Makmor Bakry

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2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)32-41
Number of pages10
JournalIndian Journal of Pharmaceutical Education and Research
Volume52
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Curcumin
Kainic Acid
Cell Death
Inflammation
Genes
Cytokines
Molecular Sequence Annotation
Interleukin-18
Gliosis
Status Epilepticus
Gene Expression Profiling
Neuroprotective Agents
Wistar Rats
Anti-Inflammatory Agents
Up-Regulation
Software
Databases
Brain

Keywords

  • Anti-epileptogenic
  • Curcumin
  • Epileptogenesis
  • Gene expression
  • Kainic acid
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

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title = "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.",
keywords = "Anti-epileptogenic, Curcumin, Epileptogenesis, Gene expression, Kainic acid, Temporal lobe epilepsy",
author = "Yow Hui-Yin and Nurulumi Ahmad and Norazrina Azmi and {Makmor Bakry}, Mohd",
year = "2018",
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language = "English",
volume = "52",
pages = "32--41",
journal = "Indian Journal of Pharmaceutical Education and Research",
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T1 - Curcumin

T2 - The molecular mechanisms of action in inflammation and cell death during kainate-induced epileptogenesis

AU - Hui-Yin, Yow

AU - Ahmad, Nurulumi

AU - Azmi, Norazrina

AU - Makmor Bakry, Mohd

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Anti-epileptogenic

KW - Curcumin

KW - Epileptogenesis

KW - Gene expression

KW - Kainic acid

KW - Temporal lobe epilepsy

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