Gallic acid, a histone acetyltransferase inhibitor, suppresses β-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation
Article first published online: 31 OCT 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 12, pages 1798–1808, December 2011
How to Cite
Kim, M.-J., Seong, A.-R., Yoo, J.-Y., Jin, C.-H., Lee, Y.-H., Kim, Y. J., Lee, J., Jun, W. J. and Yoon, H.-G. (2011), Gallic acid, a histone acetyltransferase inhibitor, suppresses β-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation. Mol. Nutr. Food Res., 55: 1798–1808. doi: 10.1002/mnfr.201100262
- Issue published online: 2 DEC 2011
- Article first published online: 31 OCT 2011
- Manuscript Accepted: 2 SEP 2011
- Manuscript Revised: 16 AUG 2011
- Manuscript Received: 19 APR 2011
- Korea Health Care Technology R&D Project
- Ministry for Health, Welfare & Family Affairs
- Republic of Korea. Grant Number: A092039
- National Research Foundation of Korea
- Korea Government (MEST). Grant Number: 2011-0030709
- Alzheimer disease;
- Gallic acid;
- Histone acetyltransferase inhibitor;
Scope: We examined the biological effect of gallic acid (GA) as a nuclear factor (NF)-κB acetyltransferase inhibitor on microglial-mediated β-amyloid neurotoxicity and restorative effects on the Aβ-induced cognitive dysfunction.
Methods and results: The protective effects of GA on the survival of neuronal cells were assessed with an MTT assay and a co-culture system. For the co-culture experiments, both BV-2 and primary microglia cells were treated with GA prior to Aβ stimulation, and conditioned media were transferred to Neuro-2A cells. The mRNA and protein levels of inflammatory cytokines in both microglia and Neuro-2A cells were assessed with real-time polymerase chain reaction and western blotting. Inhibition of nuclear factor kappa B (NF-κB) acetylation with GA treatment resulted in reduced cytokine production in microglia cells and protection of neuronal cells from Aβ-induced neurotoxicity. Furthermore, we observed a restorative effect of GA on Aβ-induced cognitive dysfunction in mice with Y-maze and passive avoidance tests. Finally, we found that GA treatment efficiently blocked neuronal cell death by downregulating the expression of cytokines and the in vivo levels of NF-κB acetylation.
Conclusion: These results suggest that selective inhibition of NF-κB acetylation by the histone acetyltransferase inhibitor GA is a possible therapeutic approach for alleviating the inflammatory progression of Alzheimer disease.